Effects of Sleep Disruption on Drug Response

• Within-Subject test of blinded study medication (Drug): On the day after each sleep condition (Uninterrupted Sleep and Sleep Disruption), participants will undergo multiple injections of study medication or placebo. This is a double-blind within-subject Phase II trial. Participants receive up to four injections, starting with placebo (saline). This is followed by ascending doses of Hydromorphone (0.14, 0.28, and 0.56mg/70kg). This study uses a within-subject design, such that participants serve as participants' own control.

Primary outcomes

• Drug Liking as Assessed by the Visual Analog Scale [up to 420 minute post-medication administration]: Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Do you like the drug?" Values reported represent average values across time points in the drug administration assessment period (up to 420 minutes).
• Heat Pain Threshold [up to 420 minute post-medication administration]: A thermode will gradually increase in temperature until the participant indicates when it "first feels painful". The outcome will be the temperature (degrees Celsius) at which the participant indicates they first feel pain. Values reported represent average values across time points in the drug administration assessment period (up to 420 minutes).
• Suprathreshold Tonic Heat Pain [up to 420 minute post-medication administration]: A painful temperature above threshold will be held tonically for a period of time, after which pain ratings are obtained on a 0-100 numerical rating scale, where 0 = "No Pain" and 100 = "Worst Pain Imaginable." Values reported represent average values across time points in the drug administration assessment period (up to 420 minutes).
• Monetary Valuation of Drug as Assessed by the Drug vs. Money Multiple Choice Questionnaire [up to 420 minute post-medication administration]: Participants are presented with an array of choices (in dollar value) which they will compare to the option of receiving study drug. They will decide for each choice whether they would take the money (at that value) or the drug they received in the session. The outcome will be the "crossover point", which is the mean of the last price that the participant selected "drug" and the first price at which the participant selected "money". Values reported represent those from a single administration following the drug administration assessment period.

Secondary outcomes

• Good Drug Effects as Assessed by the Visual Analog Scale [up to 420 minute post-medication administration]: Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Does the drug have any good effects?" Values reported represent average values across time points in the drug administration assessment period (up to 420 minutes).
• Bad Drug Effects as Assessed by the Visual Analog Scale [up to 420 minute post-medication administration]: Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Does the drug have any bad effects?" Values reported represent average values across time points in the drug administration assessment period (up to 420 minutes).
• Level of "Highness" as Assessed by Visual Analog Scale [up to 420 minute post-medication administration]: Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "How high are you?" Values reported represent average values across time points in the drug administration assessment period (up to 420 minutes).
• Feeling of Sickness as Assessed by Visual Analog Scale [up to 420 minute post-medication administration]: Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Does this drug make you feel sick?" Values reported represent average values across time points in the drug administration assessment period (up to 420 minutes).
• Clinical Pain [up to 420 minute post-medication administration]: This will be rated on a 0-100 Numerical Rating Scale, where 0 = "No Pain" and 100 = "Worst Pain Imaginable." Values reported represent average values across time points in the drug administration assessment period (up to 420 minutes).

Sex: All, ages: 18 Years to 60 Years, accepts healthy volunteers

Inclusion Criteria:

General Inclusion Criteria:

* 18-60 years old
* Less than 2 servings/day of caffeinated beverages and willing to discontinue 3 days prior to admission.

CLBP-Specific Inclusion Criteria:

* Have a physician-confirmed diagnosis of CLBP
* Report chronic low back pain.

Exclusion Criteria:

General Exclusion Criteria:

* BMI >40
* Significant medical or psychiatric morbidity within 6 months or lifetime history of bipolar disorder, psychotic disorder, seizure disorder
* Lifetime history of opioid use disorder
* Clinically significant abnormal complete blood count or comprehensive metabolic profile
* Any contraindicated medical condition (status asthmaticus; chronic obstructive pulmonary disease; reduced respiratory function; hypotension; hypertension; impairment of hepatic, pulmonary or renal functions; myxedema or hyperthyroidism; adrenocortical insufficiency; gastrointestinal obstruction; gall bladder disease; acute alcoholism; history of convulsive disorders; history of head injury)
* Current use of stimulants, opioids, benzodiazepines or other Central Nervous System (CNS) depressant
* Positive toxicology screen for opioids, stimulants, or recreational drugs
* Pregnancy or lactation
* Significant preadmission psychological distress.

Healthy Control and CLBP-Specific Exclusion Criteria:

* Report current medical/psychiatry history
* Report acute painful injury (within 3 months)
* Have a diagnosed chronic pain disorder.

Participant flow

Outcome results

• Drug Liking as Assessed by the Visual Analog Scale (Primary), Mean, score on a scale: Uninterrupted Sleep/Healthy Control 10.2 +/- 20.5; Sleep Disruption/Healthy Control 5.6 +/- 14.0; Uninterrupted Sleep/CLBP 22.2 +/- 29.1; Sleep Disruption/CLBP 16.4 +/- 23.0
• Heat Pain Threshold (Primary), Mean, degrees celsius: Uninterrupted Sleep/Healthy Controls 42.6 +/- 3.2; Sleep Disruption/Healthy Controls 41.7 +/- 3.5; Uninterrupted Sleep/CLBP 42.1 +/- 2.8; Sleep Disruption/CLBP 41.4 +/- 3.2
• Suprathreshold Tonic Heat Pain (Primary), Mean, score on a scale: Uninterrupted Sleep/Healthy Controls 46.0 +/- 23.0; Sleep Disruption/Healthy Controls 50.0 +/- 26.0; Uninterrupted Sleep/CLBP 60.0 +/- 28.0; Sleep Disruption/CLBP 63.0 +/- 29.0
• Monetary Valuation of Drug as Assessed by the Drug vs. Money Multiple Choice Questionnaire (Primary), Mean, US dollars: Uninterrupted Sleep/Healthy Controls 6.1 +/- 7.1; Sleep Disruption/Healthy Controls 3.4 +/- 6.6; Uninterrupted Sleep/CLBP 2.8 +/- 4.9; Sleep Disruption/CLBP 8.5 +/- 5.7
• Good Drug Effects as Assessed by the Visual Analog Scale (Secondary), Mean, score on a scale: Uninterrupted Sleep/Healthy Controls 8.4 +/- 17.3; Sleep Disruption/Healthy Controls 4.2 +/- 11.0; Uninterrupted Sleep/CLBP 20.5 +/- 27.6; Sleep Disruption/CLBP 11.6 +/- 21.0
• Bad Drug Effects as Assessed by the Visual Analog Scale (Secondary), Mean, score on a scale: Uninterrupted Sleep/Healthy Controls 2.9 +/- 8.4; Sleep Disruption/Healthy Controls 8.4 +/- 23.0; Uninterrupted Sleep/CLBP 7.9 +/- 16.1; Sleep Disruption/CLBP 7.9 +/- 6.0
• Level of "Highness" as Assessed by Visual Analog Scale (Secondary), Mean, score on a scale: Uninterrupted Sleep/Healthy Controls 5.8 +/- 10.9; Sleep Disruption/Healthy Controls 7.4 +/- 21.0; Uninterrupted Sleep/CLBP 10.2 +/- 17.6; Sleep Disruption/CLBP 4.9 +/- 11.0
• Feeling of Sickness as Assessed by Visual Analog Scale (Secondary), Mean, score on a scale: Uninterrupted Sleep/Healthy Controls 2.4 +/- 8.4; Sleep Disruption/Healthy Controls 7.1 +/- 22.0; Uninterrupted Sleep/CLBP 1.8 +/- 6.5; Sleep Disruption/CLBP 4.7 +/- 10.0
• Clinical Pain (Secondary), Mean, score on a scale: Uninterrupted Sleep/Healthy Controls 3.0 +/- 7.7; Sleep Disruption/Healthy Controls 1.1 +/- 3.4; Uninterrupted Sleep/CLBP 11.0 +/- 15.0; Sleep Disruption/CLBP 18.0 +/- 35.0

Adverse events

Time frame: AEs were assessed at the Opioid challenge session (Visit 2), and again after each subsequent visit (Visit 3 and Visit 4), up to 9 days. This comprises all visits in which drug administration and/or sleep manipulations occurred.

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2023-05-05)

• Michael T. Smith, PhD, Principal investigator, Johns Hopkins University

NIH grants: R01DA048206