Effects of Experimental Sleep Disturbances on Receptor Function of Study Drug

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

Interventions

BEHAVIORAL

Sleep Fragmentation

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.

DRUG

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

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).

BEHAVIORAL

Sleep Continuity Disruption

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.

BEHAVIORAL

Undisturbed Sleep

Subjects sleep normally for an 8 hour period.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Johns Hopkins University

  lead OTHER

Principal Investigators

• Eric C Strain, MD · Johns Hopkins University

• Naresh Punjabi, MD · Johns Hopkins University

• Claudia Campbell, PhD · Johns Hopkins University

• Patrick H Finan, PhD · Johns Hopkins University

• Jeannie Leoutsakos, PhD · Johns Hopkins University

• Hiroto Kuwabara, MD · Johns Hopkins University

• Alexandra Kearson, BA · Johns Hopkins University

• Michael T Smith, PhD · Johns Hopkins University

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

48 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-11-11

Primary Completion

2025-08-31

Completion

2025-08-31

FDA Drug

Yes

Countries

• United States

Study Locations