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Pilot Study of Losartan and N-acetylcysteine as Inhibitors of Muscle Oxidative Stress in Elderly

NCT01384591 — Phase 1 / Phase 2, Completed, 6 participants, The University of Texas Medical Branch, Galveston
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RegistryNCT01384591
StatusCompleted
PhasePhase 1 / Phase 2
Study typeInterventional; randomized, parallel, masking: quadruple, treatment
Enrollment6 (Actual)
SponsorThe University of Texas Medical Branch, Galveston (Other); collaborators: Lantheus Medical Imaging
ConditionsAging
InterventionsN-acetylcysteine, Losartan, Placebo losartan, Placebo N-acetylcysteine (Drug)
Datesstart 2011-07-01, primary completion 2015-05-01, completion 2015-05-01, first posted 2011-06-29, last updated 2018-05-08
Locations1 site in United States

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-Summary

The general hypothesis is that elderly have diminished nutritive flow to skeletal muscle and impaired capacity for building muscle. In aging populations, this decreased ability to build muscle may represent a tipping point in the progression towards chronic physical frailty and disability. The goal is to examine whether novel pharmacologic therapies can improve nutritive blood flow to the muscles and muscle building in the elderly.

The purpose of this study is 1) to determine if losartan administration will enhance blood flow and 2) to determine if N-acetylcysteine (NAC) will enhance blood flow.

The investigators will study community dwelling, healthy older men and women (60-85 years). Subjects will be randomized to one of three groups:

Experimental Group 1: Placebo losartan and placebo N-acetylcysteine (NAC). Experimental Group 2: losartan (25mg/dose) and placebo N-acetylcysteine (NAC). Experimental Group 3: N-acetylcysteine (NAC) (50 mg/kg/dose) and placebo

Subjects will admit to the clinic on day 1 of the study. Baseline testing consisting of leg blood flow (LBF), contrast enhanced ultrasound, handgrip testing and fatigue questionnaires. After testing is completed the subjects will recieve their first dose of NAC/ losartan/ placebo with dinner. Subjects will be fasted after 10 pm. On day 2, leg blood flow (LBF) will be measured approximately 12 hours post dose 1. Subjects will receive their second dose of NAC/ losartan/ placebo. Leg blood flow will be measured 1 hour and 2 hours post dose 2 of study interventions. The subjects will eat a meal and receive their third dose of the study intervention. Leg blood flow will be repeated at 1 hour and 2 hours post dose 3. Appoximately 30 minutes after dose 3 of the study intervention, handgrip testing will be performed and fatigue questionnaires completed.

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+Arms and interventions

ArmTypeInterventionsDescription
Losartan and placebo N-acetylcysteineExperimentalDrug: Losartan; Drug: Placebo N-acetylcysteinelosartan (25mg/dose) and placebo N-acetylcysteine (NAC) 3 total doses: 1 dose on day 1, 2 doses on day 2.
Placebo losartan and placebo N-acetylcysteinePlacebo comparatorDrug: Placebo losartan; Drug: Placebo N-acetylcysteinePlacebo losartan and placebo N-acetylcysteine (NAC) 3 total doses: 1 dose on day 1, 2 doses on day 2.
N-acetylcysteine and placebo losartanExperimentalDrug: N-acetylcysteine; Drug: Placebo losartanN-acetylcysteine (NAC) (50 mg/kg/dose) and placebo losartan 3 total doses: 1 dose on day 1, 2 doses on day 2.
  • N-acetylcysteine (Drug), also known as NAC: 50 mg/kg/dose. 3 total doses: 1 dose on day 1, 2 doses on day 2.
  • Losartan (Drug), also known as Cozaar: 25mg/dose. 3 total doses: 1 dose on day 1, 2 doses on day 2.
  • Placebo losartan (Drug), also known as Placebo: Placebo losartan 3 total doses: 1 dose on day 1, 2 doses on day 2.
  • Placebo N-acetylcysteine (Drug), also known as Placebo: Placebo N-acetylcysteine 3 total doses: 1 dose on day 1, 2 doses on day 2.

+Outcome measures

Primary outcomes

  • Leg Blood Flow as Measured by Doppler Ultrasound [Baseline]: Femoral Doppler Blood Flow was evaluated via Doppler ultrasound. For the two-dimensional (2-D) and Doppler ultrasound measurements, an ultrasound system (HDI-5000; Philips Medical Systems, Bothell, WA) with a linear array transducer (L7-4) was used with a transmit frequency of 12MHz. 2-D imaging of the common femoral artery will be performed in the long axis. Images will be triggered to the R wave of the cardiac cycle, and the femoral artery diameter will be measured using online video calipers. A pulsed-wave Doppler sample blood volume will be placed at the same location in the center of the artery, and the mean blood velocity will be measured using online angle correction and analysis software. Femoral artery mean blood flow will be calculated from 2-D and Doppler ultrasound data using the equation: Q = vπ ∙ (d/2)2, where Q is femoral blood flow, v is mean femoral artery blood flow velocity, and d is femoral artery diameter.
  • Leg Blood Flow as Measured by Doppler Ultrasound [12 hours post dose one of the intervention]: Femoral Doppler Blood Flow was evaluated via Doppler ultrasound. For the two-dimensional (2-D) and Doppler ultrasound measurements, an ultrasound system (HDI-5000; Philips Medical Systems, Bothell, WA) with a linear array transducer (L7-4) was used with a transmit frequency of 12MHz. 2-D imaging of the common femoral artery will be performed in the long axis. Images will be triggered to the R wave of the cardiac cycle, and the femoral artery diameter will be measured using online video calipers. A pulsed-wave Doppler sample blood volume will be placed at the same location in the center of the artery, and the mean blood velocity will be measured using online angle correction and analysis software. Femoral artery mean blood flow will be calculated from 2-D and Doppler ultrasound data using the equation: Q = vπ ∙ (d/2)2, where Q is femoral blood flow, v is mean femoral artery blood flow velocity, and d is femoral artery diameter.
  • Leg Blood Flow as Measured by Doppler Ultrasound [1 hour post dose two of the intervention, average of 13 hours post dose 1 of the intervention]: Femoral Doppler Blood Flow was evaluated via Doppler ultrasound. For the two-dimensional (2-D) and Doppler ultrasound measurements, an ultrasound system (HDI-5000; Philips Medical Systems, Bothell, WA) with a linear array transducer (L7-4) was used with a transmit frequency of 12MHz. 2-D imaging of the common femoral artery will be performed in the long axis. Images will be triggered to the R wave of the cardiac cycle, and the femoral artery diameter will be measured using online video calipers. A pulsed-wave Doppler sample blood volume will be placed at the same location in the center of the artery, and the mean blood velocity will be measured using online angle correction and analysis software. Femoral artery mean blood flow will be calculated from 2-D and Doppler ultrasound data using the equation: Q = vπ ∙ (d/2)2, where Q is femoral blood flow, v is mean femoral artery blood flow velocity, and d is femoral artery diameter.
  • Leg Blood Flow as Measured by Doppler Ultrasound [2 hours post dose two of the intervention, average of 14 hours post dose one of the intervention]: Femoral Doppler Blood Flow was evaluated via Doppler ultrasound. For the two-dimensional (2-D) and Doppler ultrasound measurements, an ultrasound system (HDI-5000; Philips Medical Systems, Bothell, WA) with a linear array transducer (L7-4) was used with a transmit frequency of 12MHz. 2-D imaging of the common femoral artery will be performed in the long axis. Images will be triggered to the R wave of the cardiac cycle, and the femoral artery diameter will be measured using online video calipers. A pulsed-wave Doppler sample blood volume will be placed at the same location in the center of the artery, and the mean blood velocity will be measured using online angle correction and analysis software. Femoral artery mean blood flow will be calculated from 2-D and Doppler ultrasound data using the equation: Q = vπ ∙ (d/2)2, where Q is femoral blood flow, v is mean femoral artery blood flow velocity, and d is femoral artery diameter.
  • Leg Blood Flow as Measured by Doppler Ultrasound [Post dose three of the intervention and a meal, average of 17 hours post dose one of the intervention]: Femoral Doppler Blood Flow was evaluated via Doppler ultrasound. For the two-dimensional (2-D) and Doppler ultrasound measurements, an ultrasound system (HDI-5000; Philips Medical Systems, Bothell, WA) with a linear array transducer (L7-4) was used with a transmit frequency of 12MHz. 2-D imaging of the common femoral artery will be performed in the long axis. Images will be triggered to the R wave of the cardiac cycle, and the femoral artery diameter will be measured using online video calipers. A pulsed-wave Doppler sample blood volume will be placed at the same location in the center of the artery, and the mean blood velocity will be measured using online angle correction and analysis software. Femoral artery mean blood flow will be calculated from 2-D and Doppler ultrasound data using the equation: Q = vπ ∙ (d/2)2, where Q is femoral blood flow, v is mean femoral artery blood flow velocity, and d is femoral artery diameter.
  • Leg Blood Flow as Measured by Doppler Ultrasound [1 hour post dose three of the intervention and a meal, average of 18 hours post dose one of the intervention]: Femoral Doppler Blood Flow was evaluated via Doppler ultrasound. For the two-dimensional (2-D) and Doppler ultrasound measurements, an ultrasound system (HDI-5000; Philips Medical Systems, Bothell, WA) with a linear array transducer (L7-4) was used with a transmit frequency of 12MHz. 2-D imaging of the common femoral artery will be performed in the long axis. Images will be triggered to the R wave of the cardiac cycle, and the femoral artery diameter will be measured using online video calipers. A pulsed-wave Doppler sample blood volume will be placed at the same location in the center of the artery, and the mean blood velocity will be measured using online angle correction and analysis software. Femoral artery mean blood flow will be calculated from 2-D and Doppler ultrasound data using the equation: Q = vπ ∙ (d/2)2, where Q is femoral blood flow, v is mean femoral artery blood flow velocity, and d is femoral artery diameter.
  • Leg Blood Flow as Measured by Doppler Ultrasound [2 hours post dose three of the intervention and a meal, average of 19 hours post dose one of the intervention]: Femoral Doppler Blood Flow was evaluated via Doppler ultrasound. For the two-dimensional (2-D) and Doppler ultrasound measurements, an ultrasound system (HDI-5000; Philips Medical Systems, Bothell, WA) with a linear array transducer (L7-4) was used with a transmit frequency of 12MHz. 2-D imaging of the common femoral artery will be performed in the long axis. Images will be triggered to the R wave of the cardiac cycle, and the femoral artery diameter will be measured using online video calipers. A pulsed-wave Doppler sample blood volume will be placed at the same location in the center of the artery, and the mean blood velocity will be measured using online angle correction and analysis software. Femoral artery mean blood flow will be calculated from 2-D and Doppler ultrasound data using the equation: Q = vπ ∙ (d/2)2, where Q is femoral blood flow, v is mean femoral artery blood flow velocity, and d is femoral artery diameter.

Secondary outcomes

  • Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort at Baseline [baseline]: Handgrip Strength of dominant hand is measured by handgrip dynamometry at 50% perceived effort with subjects performing one set of three contractions.
  • Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort at Baseline [baseline]: Handgrip Strength of non-dominant hand is measured by handgrip dynamometry at 50% perceived effort with subjects performing one set of three contractions.
  • Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 100% Effort at Baseline [baseline]: Handgrip Strength of dominant hand is measured by handgrip dynamometry at 100% effort with subjects performing one set of three contractions.
  • Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 100% Effort at Baseline [baseline]: Handgrip Strength of non-dominant hand is measured by handgrip dynamometry at 100% effort with subjects performing one set of three contractions.
  • Handgrip Fatigue of Dominant Hand as Measured by Handgrip Dynamometry at Baseline [baseline]: Handgrip fatigue of dominant hand as measured by handgrip dynamometry fatigue test. The non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Data is reported as % of Maximal Voluntary Contraction after fatigue test.
  • Handgrip Fatigue of Non-dominant Hand as Measured by Handgrip Dynamometry at Baseline [baseline]: Handgrip fatigue of non-dominant hand as measured by handgrip dynamometry fatigue test. The non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Data is reported as % of Maximal Voluntary Contraction (MVC) after fatigue test.
  • Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Handgrip Strength of dominant hand is measured by handgrip dynamometry at 50% perceived effort with subjects performing one set of three contractions.
  • Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Handgrip Strength of non-dominant hand is measured by handgrip dynamometry at 50% perceived effort with subjects performing one set of three contractions.
  • Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 100% Perceived Effort After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Handgrip Strength of dominant hand is measured by handgrip dynamometry at 100% perceived effort with subjects performing one set of three contractions.
  • Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 100% Perceived Effort After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Handgrip Strength of non-dominant hand is measured by handgrip dynamometry at 100% perceived effort with subjects performing one set of three contractions.
  • Handgrip Fatigue of Dominant Hand as Measured by Handgrip Dynamometry After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Handgrip fatigue of dominant hand as measured by handgrip dynamometry fatigue test. The non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Data reported as % of Maximal Voluntary Contraction (MVC) after fatigue test.
  • Handgrip Fatigue of Non-dominant Hand as Measured by Handgrip Dynamometry After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Handgrip fatigue of non-dominant hand as measured by handgrip dynamometry fatigue test. The non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Data reported as % of Maximal Voluntary Contraction (MVC) after fatigue test.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale General Fatigue at Baseline [Baseline]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the general fatigue scale is 24 to 0, with the higher number meaning more fatigue. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale General Fatigue After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the general fatigue scale is 24 to 0, with the higher number meaning more fatigue. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Physical Fatigue at Baseline [Baseline]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the physical fatigue scale is 24 to 0, with the higher number meaning more fatigue. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Physical Fatigue After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the physical fatigue scale is 24 to 0, with the higher number meaning more fatigue. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Emotional Fatigue at Baseline [Baseline]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the emotional fatigue scale is 24 to 0, with the higher number meaning more fatigue. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Emotional Fatigue After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the emotional fatigue scale is 24 to 0, with the higher number meaning more fatigue. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Mental Fatigue at Baseline [Baseline]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the mental fatigue scale is 24 to 0, with the higher number meaning more fatigue. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Mental Fatigue After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the mental fatigue scale is 24 to 0, with the higher number meaning more fatigue The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Vigor Fatigue at Baseline [Baseline]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the vigor scale is 0 to 24, with the higher number meaning more vigor. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale Vigor Fatigue After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the vigor scale is 0 to 24, with the higher number meaning more vigor. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Total Score at Baseline [Baseline]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Total Score After All Doses of Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention]: Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
  • Global Fatigue Score as Measured by Brief Fatigue Inventory at Baseline [Baseline]: The Brief Fatigue Inventory is a 9 item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life), with "0" being no fatigue and "10" being as bad as you can imagine. The Global Fatigue score is calculated by averaging the answers of all the questions. Score ranges (0 to 10) with higher score indicating a worse outcome.
  • Global Fatigue Score as Measured by Brief Fatigue Inventory After Study Invention [Post dose three of the intervention, average of 17 hours post dose one intervention]: The Brief Fatigue Inventory is a 9 item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life), with "0" being no fatigue and "10" being as bad as you can imagine. The Global Fatigue score is calculated by averaging the answers of all the questions. Score range 0 to 10, with a higher score indicating a worse outcome.
  • Perceptual Fatigue of Non-dominant Arm as Measured by Visual Analog Scale Before Handgrip Fatigue Test at Baseline. [baseline - before handgrip fatigue test]: The Visual Analog Scale for Fatigue is an 11cm long line. The subject is asked to mark their level of fatigue (0cm being no fatigue and 11cm being extreme fatigue). This test was performed before and after the handgrip fatigue test, where the non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Handgrip testing was performed at baseline (before any intervention) and post dose three of the intervention, average of 17 hours post dose one intervention.
  • Perceptual Fatigue of Non-dominant Arm as Measured by Visual Analog Scale After Handgrip Fatigue Test at Baseline. [baseline - directly after handgrip fatigue test]: The Visual Analog Scale for Fatigue is an 11cm long line. The subject is asked to mark their level of fatigue (0cm being no fatigue and 11cm being extreme fatigue). This test was performed before and after the handgrip fatigue test, where the non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Handgrip testing was performed at baseline (before any intervention) and post dose three of the intervention, average of 17 hours post dose one intervention.
  • Perceptual Fatigue of Non-dominant Arm as Measured by Visual Analog Scale Before Handgrip Fatigue Test After Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention - Before handgrip fatigue test]: The Visual Analog Scale for Fatigue is an 11cm long line. The subject is asked to mark their level of fatigue (0cm being no fatigue and 11cm being extreme fatigue). This test was performed before and after the handgrip fatigue test, where the non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Handgrip testing was performed at baseline (before any intervention) and post dose three of the intervention, average of 17 hours post dose one intervention.
  • Perceptual Fatigue of Non-dominant Arm as Measured by Visual Analog Scale After Handgrip Fatigue Test After Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention - Directly after handgrip fatigue test]: The Visual Analog Scale for Fatigue is an 11cm long line. The subject is asked to mark their level of fatigue (0cm being no fatigue and 11cm being extreme fatigue). This test was performed before and after the handgrip fatigue test, where the non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Handgrip testing was performed at baseline (before any intervention) and post dose three of the intervention, average of 17 hours post dose one intervention.
  • Perceptual Fatigue of Whole Body as Measured by Visual Analog Scale Before Handgrip Fatigue Test at Baseline. [baseline - before handgrip fatigue test]: The Visual Analog Scale for Fatigue is an 11cm long line. The subject is asked to mark their level of fatigue (0cm being no fatigue and 11cm being extreme fatigue). This test was performed before and after the handgrip fatigue test, where the non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Handgrip testing was performed at baseline (before any intervention) and post dose three of the intervention, average of 17 hours post dose one intervention.
  • Perceptual Fatigue of Whole Body as Measured by Visual Analog Scale After Handgrip Fatigue Test at Baseline. [baseline - directly after handgrip fatigue test]: The Visual Analog Scale for Fatigue is an 11cm long line. The subject is asked to mark their level of fatigue (0cm being no fatigue and 11cm being extreme fatigue). This test was performed before and after the handgrip fatigue test, where the non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Handgrip testing was performed at baseline (before any intervention) and post dose three of the intervention, average of 17 hours post dose one intervention.
  • Perceptual Fatigue of Whole Body as Measured by Visual Analog Scale Before Handgrip Fatigue Test After Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention - Before handgrip fatigue test]: The Visual Analog Scale for Fatigue is an 11cm long line. The subject is asked to mark their level of fatigue (0cm being no fatigue and 11cm being extreme fatigue). This test was performed before and after the handgrip fatigue test, where the non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Handgrip testing was performed at baseline (before any intervention) and post dose three of the intervention, average of 17 hours post dose one intervention.
  • Perceptual Fatigue of Whole Body as Measured by Visual Analog Scale After Handgrip Fatigue Test After Study Intervention [Post dose three of the intervention, average of 17 hours post dose one intervention - Directly after handgrip fatigue test]: The Visual Analog Scale for Fatigue is an 11cm long line. The subject is asked to mark their level of fatigue (0cm being no fatigue and 11cm being extreme fatigue). This test was performed before and after the handgrip fatigue test, where the non-dominant hand hold a continuous contraction at 20% of the subjects maximal voluntary contraction for 5 minutes. Handgrip testing was performed at baseline (before any intervention) and post dose three of the intervention, average of 17 hours post dose one intervention.

+Eligibility

Sex: All, ages: 60 Years to 85 Years, accepts healthy volunteers

Inclusion Criteria:

1. Age between 60-85 years.
2. Ability to sign informed consent.
3. Ability to sign consent form.
4. Ability to pass a mini-mental status exam (score >23 on the 30-item Mini Mental State Examination, MMSE).
5. Free-living, prior to admission.

Exclusion Criteria:

1. Subjects with cardiac abnormalities considered exclusionary by the study physicians (e.g., unstable angina or a cardiology-confirmed ECG that demonstrates cardiac abnormalities such as > 0.2 mV horizontal or downsloping ST segment depression, frequent arrhythmia's (> 10 PVC/min), or valvular disease).
2. Subjects with uncontrolled metabolic disease, including liver or renal disease.
3. Subjects with vascular disease characterized by a combination of risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, uncontrolled diabetes, hypercholesterolemia > 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal, and pedal arteries.
4. Any history of hypo- or hyper-coagulation disorders. (e.g., Coumadin use or history of DVT or PE).
5. Subjects with chronically elevated systolic pressure >170 or a diastolic blood pressure > 100. Subjects may be included if they are taking medication and have a blood pressure below these criteria.
6. Subjects with cancer or recently (6 months) treated cancer other than basal cell carcinoma.
7. Any subject currently on a weight-loss diet or a body mass index > 33 kg/m2.
8. Inability to abstain from smoking for duration of study.
9. A history of > 20 pack per year smoking.
10. Subjects with atrial fibrillation, history of syncope, angina, or congestive heart failure.
11. Any subject that is HIV-seropositive or has active hepatitis.
12. Recent anabolic or corticosteroids use (within 3 months).
13. Subjects with low hemoglobin or hematocrit (i.e., lower than accepted lab values).
14. Agitation/aggression disorder.
15. Dementia.
16. History of stroke with motor disability.
17. A recent history (<12 months) of GI bleed.
18. Alcohol (more than 3 drinks per day) or drug abuse.
19. Polycystic ovary syndrome (PCOS) and/or hyperthecosis.
20. Non-classical adrenal hyperplasia.
21. Cushing's syndrome.
22. Pregnancy.
23. Hyperprolactinoma, hypothyroidism.
24. Lactose intolerance.
25. Subjects with coronary heart or mitral valvular rheumatic heart disease.
26. Subjects with impaired renal function and/or renal artery stenosis.
27. Subjects with pulmonary hypertension.
28. Subjects on any medications known to vasodilate the peripheral arteries.
29. Subjects taking NSAIDs
30. Physical dependence or frailty (impairment of activities of daily living, ADLs).
31. History of falls (>2/year).
32. Depression (>5 of the 15 items on the Geriatric Depression Scale (GDS).
33. Subjects suffering malnutrition or with a BMI < 20 kg/m2 with low albumin or transferrin.
34. Asthma
35. Any other condition or event considered exclusionary by the PI and covering faculty physician.

+Posted results

Participant flow

MilestoneLosartan and Placebo N-acetylcysteinePlacebo Losartan and Placebo N-acetylcysteineN-acetylcysteine and Placebo Losartan
Started222
Completed222
Not completed000

Outcome results

  • Leg Blood Flow as Measured by Doppler Ultrasound (Primary), Mean, ml/minute: Placebo Losartan and Placebo N-acetylcysteine 174.99 +/- 176.02; N-acetylcysteine and Placebo Losartan 102.08 +/- 3.42; Losartan and Placebo N-acetylcysteine 428.45 +/- 114.57
  • Leg Blood Flow as Measured by Doppler Ultrasound (Primary), Mean, ml/minute: Placebo Losartan and Placebo N-acetylcysteine 181.88 +/- 204.92; N-acetylcysteine and Placebo Losartan 69.83 +/- 77.57; Losartan and Placebo N-acetylcysteine 91.68 +/- 4.88
  • Leg Blood Flow as Measured by Doppler Ultrasound (Primary), Mean, ml/minute: Placebo Losartan and Placebo N-acetylcysteine 105.80; N-acetylcysteine and Placebo Losartan 90.06 +/- 39.19; Losartan and Placebo N-acetylcysteine 95.60 +/- 64.67
  • Leg Blood Flow as Measured by Doppler Ultrasound (Primary), Mean, ml/minute: Placebo Losartan and Placebo N-acetylcysteine 214.56 +/- 88.42; N-acetylcysteine and Placebo Losartan 70.37 +/- 15.35; Losartan and Placebo N-acetylcysteine 114.34 +/- 38.71
  • Leg Blood Flow as Measured by Doppler Ultrasound (Primary), Mean, ml/minute: Placebo Losartan and Placebo N-acetylcysteine 158.71 +/- 83.85; N-acetylcysteine and Placebo Losartan 109.94 +/- 59.51; Losartan and Placebo N-acetylcysteine 153.38 +/- 103.37
  • Leg Blood Flow as Measured by Doppler Ultrasound (Primary), Mean, ml/minute: Placebo Losartan and Placebo N-acetylcysteine 84.41 +/- 18.57; N-acetylcysteine and Placebo Losartan 104.40 +/- 56.55; Losartan and Placebo N-acetylcysteine 152.10 +/- 46.59
  • Leg Blood Flow as Measured by Doppler Ultrasound (Primary), Mean, ml/minute: Placebo Losartan and Placebo N-acetylcysteine 70.60 +/- 17.46; N-acetylcysteine and Placebo Losartan 128.78 +/- 123.74; Losartan and Placebo N-acetylcysteine 57.79 +/- 29.24
  • Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort at Baseline (Secondary), Mean, kilograms: Placebo Losartan and Placebo N-acetylcysteine 21.5 +/- 6.5; N-acetylcysteine and Placebo Losartan 23.2 +/- 4.9; Losartan and Placebo N-acetylcysteine 20.5 +/- 16.7
  • Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort at Baseline (Secondary), Mean, kilograms: Placebo Losartan and Placebo N-acetylcysteine 24.2 +/- 2.6; N-acetylcysteine and Placebo Losartan 19.3 +/- 1.9; Losartan and Placebo N-acetylcysteine 17.0 +/- 15.1
  • Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 100% Effort at Baseline (Secondary), Mean, kilograms: Placebo Losartan and Placebo N-acetylcysteine 45.2 +/- 8.2; N-acetylcysteine and Placebo Losartan 33.2 +/- 4.0; Losartan and Placebo N-acetylcysteine 28.8 +/- 13.9
  • Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 100% Effort at Baseline (Secondary), Mean, kilograms: Placebo Losartan and Placebo N-acetylcysteine 47.1 +/- 7.9; N-acetylcysteine and Placebo Losartan 31.1 +/- 0.8; Losartan and Placebo N-acetylcysteine 26.5 +/- 11.1
  • Handgrip Fatigue of Dominant Hand as Measured by Handgrip Dynamometry at Baseline (Secondary), Mean, % of Maximal Voluntary Contraction: Placebo Losartan and Placebo N-acetylcysteine 129.6; N-acetylcysteine and Placebo Losartan 94.2 +/- 12.06; Losartan and Placebo N-acetylcysteine 103.4
  • Handgrip Fatigue of Non-dominant Hand as Measured by Handgrip Dynamometry at Baseline (Secondary), Mean, % of Maximal Voluntary Contraction: Placebo Losartan and Placebo N-acetylcysteine 64.55; N-acetylcysteine and Placebo Losartan 83.62 +/- 2.33; Losartan and Placebo N-acetylcysteine 90.29
  • Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort After All Doses of Study Intervention (Secondary), Mean, kilograms: Placebo Losartan and Placebo N-acetylcysteine 21.2 +/- 13.9; N-acetylcysteine and Placebo Losartan 15.8 +/- 1.6; Losartan and Placebo N-acetylcysteine 16.2 +/- 11.1
  • Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 50% Perceived Effort After All Doses of Study Intervention (Secondary), Mean, kilograms: Placebo Losartan and Placebo N-acetylcysteine 17.8 +/- 4.5; N-acetylcysteine and Placebo Losartan 14.8 +/- 4.5; Losartan and Placebo N-acetylcysteine 13.7 +/- 7.1
  • Handgrip Strength of Dominant Hand as Measured by Handgrip Dynamometry at 100% Perceived Effort After All Doses of Study Intervention (Secondary), Mean, kilograms: Placebo Losartan and Placebo N-acetylcysteine 44.1 +/- 6.2; N-acetylcysteine and Placebo Losartan 31.3 +/- 6.6; Losartan and Placebo N-acetylcysteine 24.2 +/- 13.0
  • Handgrip Strength of Non-dominant Hand as Measured by Handgrip Dynamometry at 100% Perceived Effort After All Doses of Study Intervention (Secondary), Mean, kilograms: Placebo Losartan and Placebo N-acetylcysteine 42.3 +/- 3.9; N-acetylcysteine and Placebo Losartan 28.6 +/- 2.7; Losartan and Placebo N-acetylcysteine 30.2 +/- 0.2
  • Handgrip Fatigue of Dominant Hand as Measured by Handgrip Dynamometry After All Doses of Study Intervention (Secondary), Mean, % of Maximal Voluntary Contraction: Placebo Losartan and Placebo N-acetylcysteine 101.0; N-acetylcysteine and Placebo Losartan 95.97 +/- 2.16; Losartan and Placebo N-acetylcysteine 111
  • Handgrip Fatigue of Non-dominant Hand as Measured by Handgrip Dynamometry After All Doses of Study Intervention (Secondary), Mean, % of Maximal Voluntary Contraction: Placebo Losartan and Placebo N-acetylcysteine 88.61; N-acetylcysteine and Placebo Losartan 93.25 +/- 11.32; Losartan and Placebo N-acetylcysteine 95.60
  • Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory - Subscale General Fatigue at Baseline (Secondary), Mean, units on a scale: Placebo Losartan and Placebo N-acetylcysteine 0 +/- 0; N-acetylcysteine and Placebo Losartan 1.5 +/- 2.12; Losartan and Placebo N-acetylcysteine 3.5 +/- 2.11
  • 21 more outcome measures not shown.

Adverse events

ArmDeathsSerious adverse eventsOther adverse events
Placebo Losartan and Placebo N-acetylcysteine0/2 (0.0%)0/2 (0.0%)1/2 (50.0%)
N-acetylcysteine and Placebo Losartan0/2 (0.0%)0/2 (0.0%)0/2 (0.0%)
Losartan and Placebo N-acetylcysteine0/2 (0.0%)0/2 (0.0%)0/2 (0.0%)

Other adverse events by term

TermOrgan systemPlacebo Losartan and Placebo N-acetylcysteineN-acetylcysteine and Placebo LosartanLosartan and Placebo N-acetylcysteine
RashSkin and subcutaneous tissue disorders1/20/20/2

+Locations (1)

FacilityCityCountryStatus
University of Texas Medical BranchGalveston, TexasUnited States

+Investigators

My Notes