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Effects of Experimental Sleep Disturbances on Receptor Function of Study Drug (Sleep-MOR)

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ClinicalTrials.gov Identifier: NCT04299490
Recruitment Status : Recruiting
First Posted : March 6, 2020
Last Update Posted : December 19, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Johns Hopkins University

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.

Condition or disease Intervention/treatment Phase
Sleep Disorder Healthy Behavioral: Sleep Fragmentation Drug: Within-Subject test of blinded study medication (stimulant, benzodiazepine, opioid, cannabinoid, over-the-counter pain medication, or placebo) Behavioral: Sleep Continuity Disruption Behavioral: Undisturbed Sleep Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Experimental Sleep Disruption and Fragmentation on Study Drug Receptor Function, Receptor Agonist Analgesia, and Abuse Liability
Actual Study Start Date : November 11, 2020
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : January 31, 2023

Arm Intervention/treatment
Experimental: Sleep Continuity Disruption
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)
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.

Experimental: Sleep Fragmentation
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
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).

Active Comparator: Undisturbed Sleep
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)
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: Undisturbed Sleep
Subjects sleep normally for an 8 hour period.




Primary Outcome Measures :
  1. Percent change in receptor binding potential from PET scan [ Time Frame: Up to 90 minutes on Day 3 of inpatient visit ]
    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.

  2. Withdrawal Latency measured in seconds during Cold Pressor Pain Tolerance test [ Time Frame: Up to 270 minutes post-medication administration ]
    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.

  3. Drug Effects as assessed by the Visual Analog Scale [ Time Frame: Up to 270 minutes post-medication administration ]
    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).

  4. The monetary valuation in dollars of the study medication as assessed by the Drug or Money Multiple Choice Questionnaire [ Time Frame: 150 minutes after final dose administration ]
    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.



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Ages Eligible for Study:   18 Years to 48 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Had exposure to ionizing radiation that in combination with the study's estimated radiation exposure would result in a cumulative exposure, exceeding recommended limits
  • Unable to tolerate the scanning environment/ claustrophobia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04299490


Contacts
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Contact: Michael T Smith, PhD 4105507000 msmith62@jhmi.edu
Contact: Nicholas G Wolf, BA 4105506246 nwolf5@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins School of Medicine Recruiting
Baltimore, Maryland, United States, 21224
Contact: Michael T Smith, PhD    410-550-7000    msmith62@jhmi.edu   
Principal Investigator: Michael T Smith, PhD         
Sponsors and Collaborators
Johns Hopkins University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Study Chair: 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
Principal Investigator: Michael T Smith, PhD Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04299490    
Other Study ID Numbers: IRB00224309
1U01HL150568-01 ( U.S. NIH Grant/Contract )
First Posted: March 6, 2020    Key Record Dates
Last Update Posted: December 19, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Johns Hopkins University:
Insomnia
Sleep Apnea
Sleep disturbances
Pain
Analgesia
Drug Abuse Liability
Additional relevant MeSH terms:
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Sleep Wake Disorders
Nervous System Diseases
Neurologic Manifestations
Mental Disorders
Analgesics
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents