Effects of Sleep Disruption on Drug Response

NCT03680287 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: IRB00160629R01DA048206
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

The central scientific premise of the proposed study is that sleep disruption (SD) will influence individuals' subjective response to blinded medication administration. The investigators further believe these responses will vary among patients who have chronic low back pain (CLBP) vs. healthy controls, and that sex will moderate effects. The proposed study evaluates whether CLBP patients' subjective responses to study medication administration are altered by SD. The investigators focus on two outcome domains: abuse liability (i.e., drug liking and valuation) and response to pain testing. The investigators propose a mixed between-within randomized crossover human-laboratory experiment that investigates placebo-controlled effects of study medication on 1) abuse liability metrics (Drug Liking and Monetary Valuation) and 2) response to laboratory-evoked standardized pain measures, after one night of uninterrupted sleep (US) and again after one night of SD. The investigators will recruit both CLBP patients(\*) and healthy controls (N = 60). (\*) We originally aimed to accrue 60 subjects with CLBP. However, we have been granted approval by the National Institute on Drug Abuse (NIDA) to reduce expectations for the target N for the CLBP cohort. We are no longer expected to recruit N=60 CLBP participants; this is a COVID-19 modification, and we are not required to re-do a power analysis.

Conditions

Low Back Pain, Recurrent; Healthy

Outcome Measures

Primary Outcomes (4)

• Drug Liking as assessed by the Visual Analog Scale

  Visual Analog Scale (0-100), where 0=None and 100 = Extremely , in response to the question, "Do you like the drug?"

  up to 420 minute post-medication administration

• Heat Pain Threshold

  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.

  up to 420 minute post-medication administration

• Suprathreshold Tonic Heat Pain

  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."

  up to 420 minute post-medication administration

• Monetary Valuation of Drug as assessed by the Drug vs. Money Multiple Choice Questionnaire

  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".

  up to 420 minute post-medication administration

Secondary Outcomes (5)

• Good Drug Effects as assessed by the Visual Analog Scale

  up to 420 minute post-medication administration

• Bad Drug Effects as assessed by the Visual Analog Scale

  up to 420 minute post-medication administration

• Level of "Highness" as assessed by Visual Analog Scale

  up to 420 minute post-medication administration

• Feeling of Sickness as assessed by Visual Analog Scale

  up to 420 minute post-medication administration

• Clinical Pain

  up to 420 minute post-medication administration

Study Arms (2)

Uninterrupted Sleep

ACTIVE COMPARATOR

Participants will be permitted to sleep without interruption for 8 hours.

Drug: Within-Subject test of blinded study medication

Sleep Disruption

EXPERIMENTAL

Participants will be repeatedly awakened throughout the night according to a standardized protocol.

Drug: Within-Subject test of blinded study medication

Interventions

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. As such, study medications must remain blinded. Participants may receive a medication from one or more of the following categories: prescription stimulants, prescription benzodiazepines, prescription opioids, prescription cannabinoids, over-the-counter medications, or placebo (saline). This study uses a within-subject design, such that participants serve as participants' own control.

Sleep Disruption; Uninterrupted Sleep

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years old
• Less than 2 servings/day of caffeinated beverages and willing to discontinue 3 days prior to admission.
• Have a physician-confirmed diagnosis of CLBP
• Report chronic low back pain.

You may not qualify if:

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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Johns Hopkins School of Medicine

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Low Back Pain

Condition Hierarchy (Ancestors)

Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael T. Smith, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2018
• First Posted: September 21, 2018
• Study Start: October 7, 2019
• Primary Completion: April 29, 2025
• Study Completion: April 29, 2025
• Last Updated: July 7, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)