Enhancing Functional Capacity in Older Adults With Short Session High Intensity Interval Training

Enhancing functional capacity in older adults with short session high intensity interval training

Frailty is a condition of poor physiological reserve that increases susceptibility to falls, hospitalization, disability and mortality. The incidence of frailty rapidly increases after the age 65, growing from 10% to as many as 50% of those 85 years or older; therefore over 9 million Veterans are either frail or at risk for frailty. Exercise has proven benefits for frailty, yet older adults rarely attain the recommended 150 minutes a week of moderate intensity exercise. High intensity interval training (HIIT) is emerging as an alternative as it delivers similar or better gains than moderate intensity exercise in less time. Recently, the investigators published that a 3-day-a-week, 10-minute HIIT regimen in aged mice not only reduces frailty, but leads to both strength and endurance benefits. In addition, the preliminary data demonstrate significant changes in microRNA (miRNA) profiles. Despite the potential of short session HIIT to improve functional capacity and lead to better adherence, the modality has not been tested in individuals 65-85 years of age, and in particular, frail individuals. The goals of this proposal are to: 1) investigate the feasibility of recruiting and administering short session HIIT to frail, pre-frail, and non-frail older Veterans and 2) to characterize the physical performance benefits and serum microRNA (miRNA) profiles in those participants.

To accomplish these goals the investigators will administer a short session HIIT regimen totaling only 10-minutes, 3-days-a-week for 3 months, using recumbent exercise cycles, to 65-85 year old participants. The investigators will also utilize next generation RNA sequence technology to assess HIIT impacts upon microRNA profiles in serum samples. The investigators anticipate this project will demonstrate the feasibility of administering short session HIIT to older individuals, including vulnerable frail and pre-frail populations as well as demonstrate the ability to collect and analyze serum miRNA profiles. The advantages to this program are the ability to maintain or build muscle mass and improve aerobic conditioning, especially in older patients where frailty and sarcopenia are so prevalent. This pilot project will therefore lay the foundation for future clinical trials that further explore the utility of HIIT to prevent or delay the onset of frailty in larger cohorts, and ultimately lead to the enhancement of functional capacity and quality of life in aging Veteran populations.

• Short session HIIT (Behavioral): Individually tailored short session high intensity interval training session 3 times per week for 12 weeks on a recumbent exercise cycle.

Primary outcomes

• 6-minute Walk at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: 6-minute walk, total distance over 6 minutes in a 50 foot long hallway, participants asked to walk at a "brisk" pace.
• Physical Activity Enjoyment at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Physical Activity Enjoyment Scale (PACES) that provides a valid instrument for assessing enjoyment in physical activity. There are 18 questions, each of which can receive a score from 1 to 7, where 7 is represents greater enjoyment. Scores presented as the mean across all questions giving an overall range of 1-7.
• VO2max at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Performed as part of a symptom limited maximal endurance test on a cycle ergometer

Secondary outcomes

• Short Physical Performance Battery at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Short Physical Performance Battery (SPPB) is an objective assessment tool for evaluating lower extremity functioning in older persons, including balance, side-by-side/semi-tandem/tandem stands, and gait speed. There are 3 subscales, each of which can receive from 0 to 4 points. Therefore the total range of the test spans summed scores from 0 to 12, where 12 is the best outcome.
• Frailty at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Fried frailty phenotype assessment includes: gait speed, grip strength, endurance, activity level, weight loss. These assessments report summed scores of 0 to 5, where 0 is the best outcome. If gait speed or grip strength (m/sec or kg) falls within the lowest quintile (20%) for the age and gender adjusted range, then it is given a score of "1". If both questions on the endurance or activity measures are positive then then it is given a score of "1". If weight loss is greater than 5% over the past year, then it is given a score of "1".
• Quality of Life Survey at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF). There are 14 subscales with scores of 1 to 5, where 5 is the better outcome. Therefore the total range of the test spans scores from 14 to 70, where 70 is the best outcome. The final score as a percentage with range being 0-100% and top being 100%. This percentage is calculated as: 100 * ((participant's score - 14) / 56).
• Cognitive Survey at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: VA-SLUMS: VA Saint Louis University Mental Status screen. Survey includes 11 questions allowing a range of scores from 1-30 points, where higher scores represent greater mental outcomes.
• Activities of Daily Living & Instrumental Activities of Daily Living Survey at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: The Activities of Daily living and instrumental activities of daily living are a survey comprised of 14 questions including ability to: dress, eat, ambulate, toilet, hygiene, shop, housework, accounting, food preparation, and use transportation/telephone. Each question gives up to 1 point with a total range of 0-14. Higher scores indicate less independence and greater reliance on support.
• microRNA Profiling at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Next Generation Sequencing of microRNA species from serum.
• Serum 25-hydroxy-vitamin D at Baseline [baseline]: serum 25-hydroxy-vitamin D was measured from serum isolated from blood collected at baseline and measured using ELISA
• C-reactive Protein Level at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: C-reactive protein was measured from isolated serum samples at baseline and endpoint using ELISA
• Quadriceps Strength at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Maximal quadriceps strength. This will be measured with the MicroFET2 dynamometer with a readout in kilograms (kg) of force.
• FRAIL Scale Survey at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: FRAIL scale: fatigability, resistance, ambulation, illnesses, loss of weight. If the answers to any of the questions is yes, then given score is "1" with a total survey range of 0 to 5. Higher scores represent greater frailty.
• Serum Interleukin-6 Level at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Interleukin-6 collected from serum extracted from blood samples taken at baseline and endpoint and measured using ELISA
• Serum Interleukin-10 Level at Baseline and Endpoint [baseline and at participant completion, an average of 3 months]: Interleukin-10 collected from serum extracted from blood samples taken at baseline and endpoint and measured using ELISA
• Number of Participants With Muscle Tissue Oxygenation Raw Data Collected [baseline and at participant completion, an average of 3 months]: Seeking to collect raw data using functional near infra-red spectroscopy to analyze quadriceps during VO2max test. This work is the first steps in the development of techniques that analyze muscle blood flow and tissue oxygenation during exercise.

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

Inclusion Criteria:

* Male or female
* Any race
* Frail, pre-frail, and non-frail
* Medical clearance for exercise

Exclusion Criteria:

* Severe co-morbidity (e.g. - CHF (class III), COPD (GOLD stage IV), CKD (stage 3))
* VAMC SLUMS score 20
* Physical impairment that prevents use of a recumbent exercise bike

Participant flow

Outcome results

• 6-minute Walk at Baseline and Endpoint (Primary), Mean, meters: HIIT Intervention 418.2 +/- 72.2 (p 0.0238)
• Physical Activity Enjoyment at Baseline and Endpoint (Primary), Mean, Scores on a scale: HIIT Intervention 6.1 +/- 0.8 (p 0.3029)
• VO2max at Baseline and Endpoint (Primary), Mean, mL/min/kg: HIIT Intervention 18.67 +/- 5.12 (p 0.1713)
• Short Physical Performance Battery at Baseline and Endpoint (Secondary), Mean, score on a scale: HIIT Intervention 10.11 +/- 2.0 (p 0.1261)
• Frailty at Baseline and Endpoint (Secondary), Mean, score on a scale: HIIT Intervention 0.87 +/- 0.8 (p 0.1367)
• Quality of Life Survey at Baseline and Endpoint (Secondary), Mean, % of Max Score: HIIT Intervention 80.0 +/- 11.4 (p 0.0111)
• Cognitive Survey at Baseline and Endpoint (Secondary), Mean, score on a scale: HIIT Intervention 26.6 +/- 2.5 (p 0.0219)
• Activities of Daily Living & Instrumental Activities of Daily Living Survey at Baseline and Endpoint (Secondary), Mean, Score on a scale: HIIT Intervention 0.04 +/- 0.21 (p 0.3660)
• microRNA Profiling at Baseline and Endpoint (Secondary)
• Serum 25-hydroxy-vitamin D at Baseline (Secondary), Mean, ng/ml: HIIT Intervention 26.9 +/- 15.2
• C-reactive Protein Level at Baseline and Endpoint (Secondary), Mean, ug/uL: HIIT Intervention 3.0 +/- 3.5 (p 0.1563)
• Quadriceps Strength at Baseline and Endpoint (Secondary), Mean, kg: HIIT Intervention 27.7 +/- 6.8 (p 0.0110)
• FRAIL Scale Survey at Baseline and Endpoint (Secondary), Mean, Score on a scale: HIIT Intervention 0.2 +/- 0.4 (p 0.3282)
• Serum Interleukin-6 Level at Baseline and Endpoint (Secondary), Mean, pg/mL: HIIT Intervention 3.8 +/- 1.9 (p 0.5244)
• Serum Interleukin-10 Level at Baseline and Endpoint (Secondary), Mean, pg/mL: HIIT Intervention 3.0 +/- 0.9 (p 0.5718)
• Number of Participants With Muscle Tissue Oxygenation Raw Data Collected (Secondary), Count of participants, Participants: HIIT Intervention 10

Adverse events

Time frame: Adverse event data were collected weekly over a 14 week period for each participant, commencing from baseline assessments week 0, through the HIIT intervention (weeks 1 - 12 or up to 14), and ending with collection at end-point assessments.

Limitations and caveats: Goal of trial was to evaluate recruitment, administration, and safety profile of short session HIIT, and not necessarily the efficacy of the HIIT protocol for functional capacity. Trial does not have a non-exercise control group Trial features limited number of participants (23), which includes only 1 female Trial was stopped short due to COVID-19 pandemic, 8 of the 23 participants did not complete the total 12 weeks of training although all participants had at least 6 weeks of training.

• Study Protocol and Statistical Analysis Plan (PDF, 2022-01-25)
• Informed Consent Form (PDF, 2021-11-17)

• Bruce R. Troen, MD, Principal investigator, VA Western New York Healthcare System, Buffalo, NY