Effects of Experimental Sleep Disturbances on Receptor Function of Study Drug

NCT04299490 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: IRB002243091U01HL150568-01
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this project is to determine whether common sleep disturbance patterns, sleep continuity disturbance (SCD) and Sleep Fragmentation (SF), alter cerebral study drug receptor availability, drug-based analgesia, and drug abuse liability. The investigators specifically aim to: 1) evaluate whether experimental SCD and/or SF alter resting or pain-evoked receptor binding potential in brain regions associated with pain inhibition; 2) examine whether SCD and/or SF alters the analgesic response and abuse liability profile of a study medication; and 3) determine whether receptor binding potentials in brain regions of interest are associated with study medication analgesia and abuse liability. The investigators will also evaluate the extent to which associations differ by sleep condition or sex.

Conditions

Sleep Disorder; Healthy

Keywords

Insomnia; Sleep Apnea; Sleep disturbances; Pain; Analgesia; Drug Abuse Liability

Outcome Measures

Primary Outcomes (4)

• Percent change in receptor binding potential from PET scan

  The primary dependent measures are the percent change in binding potential of study PET ligand during basal (first 45 minutes) and pain conditions (second 45 minutes) in brain regions of interest. Percent change in binding potential will be assessed between first and second 45 minutes of the 90 minutes assessment session.

  Up to 90 minutes on Day 3 of inpatient visit

• Withdrawal Latency measured in seconds during Cold Pressor Pain Tolerance test

  The primary measure of study drug analgesia is Cold Pain Threshold withdrawal latency, measured in seconds during the drug administration process. Subjects will immerse their non-dominant hand in a circulating, cold water bath for as long as possible according to standard procedures. The difference in time from when participants first feel pain to when withdraw their hand is recorded as the withdrawal latency.

  Up to 270 minutes post-medication administration

• Drug Effects as assessed by the Visual Analog Scale

  Drug abuse liability will be assessed with standard visual analog scales (VAS) using a 100-mm line marked at either end with "none"(0) and "extremely" (100).

  Up to 270 minutes post-medication administration

• The monetary valuation in dollars of the study medication as assessed by the Drug or Money Multiple Choice Questionnaire

  The Monetary Valuation of the study medication will be assessed with the Drug or Money Multiple Choice Questionnaire, commonly used in abuse liability testing. Participants indicate on a sliding scale a monetary value (range $0 to "more than $30") above which they would prefer money and below which they would prefer the drug.

  150 minutes after final dose administration

Study Arms (3)

Sleep Continuity Disruption

EXPERIMENTAL

The Sleep Continuity Disruption condition will be conducted on two consecutive nights. An 8-hour sleep opportunity period will be disturbed by several forced awakenings at random intervals during which no sleep is permitted.

Drug: Within-Subject test of blinded study medication (stimulant, benzodiazepine, opioid, cannabinoid, over-the-counter pain medication, or placebo); Behavioral: Sleep Continuity Disruption

Sleep Fragmentation

EXPERIMENTAL

The Sleep fragmentation condition will be conducted on two consecutive nights. Subjects are provided an 8-hour sleep opportunity during which their sleep will be disturbed by microarousals that simulate sleep apnea.

Behavioral: Sleep Fragmentation; Drug: Within-Subject test of blinded study medication (stimulant, benzodiazepine, opioid, cannabinoid, over-the-counter pain medication, or placebo)

Undisturbed Sleep

ACTIVE COMPARATOR

An 8-hour period of undisturbed sleep is permitted on each night.

Drug: Within-Subject test of blinded study medication (stimulant, benzodiazepine, opioid, cannabinoid, over-the-counter pain medication, or placebo); Behavioral: Undisturbed Sleep

Interventions

Sleep Fragmentation BEHAVIORAL

Subjects are provided an 8-hour sleep opportunity. Two speakers are placed 12 inches from the head of the bed and four remote-activated mechanical vibrators are placed underneath the mattress. EEG microarousals (\>3 s), as defined according to standard criteria, are elicited at a frequency of 30 or more events per hour.

Sleep Fragmentation

Within-Subject test of blinded study medication (stimulant, benzodiazepine, opioid, cannabinoid, over-the-counter pain medication, or placebo) DRUG

On the third day of the in-patient visit 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 pain medications, or placebo (saline).

Sleep Continuity Disruption; Sleep Fragmentation; Undisturbed Sleep

Sleep Continuity Disruption BEHAVIORAL

An 8-hour sleep opportunity period starting from lights out is divided into eight, one-hour intervals. One of the intervals is randomly determined to be a 60 minute forced awakening, during which no sleep is permitted. Each of the remaining seven, 60-minute intervals are subdivided into tertiles (20 min. blocks). A 20-min forced awakening (FA) is randomly scheduled to occur in either the 1st, 2nd, or 3rd tertile of each hour. During FAs, staff keep subjects awake, either by voice or gentle shaking.

Sleep Continuity Disruption

Undisturbed Sleep BEHAVIORAL

Subjects sleep normally for an 8 hour period.

Undisturbed Sleep

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, 18-48 year olds meeting criteria for Normal Sleep
• Sleep phase within 21:00 and 08:00
• Total sleep time \>6.5 and ≤8.5 hours/night; sleep efficiency ≥85%
• Non-smokers/nicotine users
• Low caffeine users (≤ 2 cups, q.d.).
• Life-time history of exposure to opioids, appropriately prescribed for pain.

You may not qualify if:

• BMI \>35
• Lifetime history of chronic pain
• Acute pain
• Meet clinical criteria for a sleep disorder
• Significant central nervous system disease (e.g., lupus, multiple sclerosis)
• Cognitive impairment, brain injury or history of closed head injury with loss of consciousness over 3 mins
• Other significant medical or psychiatric morbidity within 6 months or lifetime history of bipolar disorder, psychotic disorder, seizure disorder
• Use in the last three months of the following: antidepressants, neuroleptics, sedative hypnotics, isoniazid, glucocorticoids, psychostimulants, opioids
• Any contraindicated medical condition
• Lifetime history of alcohol or substance used disorder
• Clinically significant abnormal complete blood count, hepatic, renal or metabolic panel
• Positive toxicology screen for opioids or recreational drugs
• Pregnant or lactating women
• Significant preadmission psychological distress
• Embedded metal objects or fragments or electronic devices in the head or body that would present a risk during MRI

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Johns Hopkins School of Medicine

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Sleep Apnea Syndromes; Parasomnias; Pain; Agnosia

Interventions

Central Nervous System Stimulants; Benzodiazepines; Analgesics, Opioid; Cannabinoids

Condition Hierarchy (Ancestors)

Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Apnea; Respiration Disorders; Respiratory Tract Diseases; Perceptual Disorders; Neurobehavioral Manifestations

Intervention Hierarchy (Ancestors)

Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Narcotics; Central Nervous System Depressants; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Eric C Strain, MD

  Johns Hopkins University

  STUDY CHAIR

• Naresh Punjabi, MD

  Johns Hopkins University

  STUDY CHAIR

• Claudia Campbell, PhD

  Johns Hopkins University

  STUDY CHAIR

• Patrick H Finan, PhD

  Johns Hopkins University

  STUDY CHAIR

• Jeannie Leoutsakos, PhD

  Johns Hopkins University

  STUDY CHAIR

• Hiroto Kuwabara, MD

  Johns Hopkins University

  STUDY CHAIR

• Alexandra Kearson, BA

  Johns Hopkins University

  STUDY CHAIR

• Michael T Smith, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 6, 2020
• Study Start: November 11, 2020
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)