Mechanisms of Sleep Disruption Hyperalgesia

NCT ID: NCT01794689

Last Updated: 2019-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2019-03-12

Brief Summary

Twenty percent of Americans suffer from chronic pain. Sleep disturbance is similarly prevalent and among the most common and disabling neurobehavioral problems associated with chronic pain. This research is designed to evaluate the effects of disrupted sleep patterns on mood, inflammation, the perception of pain, and pain relief. This study will help researchers understand the relationship between sleep and pain, and how sleep disturbance might influence chronic pain conditions.

Detailed Description

This research is being conducted in order to evaluate the effects of disrupted sleep patterns on mood, inflammation, the perception of pain, and pain relief. This study will help researchers understand the relationship between sleep and pain, and how sleep disturbance might influence chronic pain conditions. Healthy participants will undergo baseline sleep and sleep disruption conditions. Following undisturbed sleep and sleep disruption conditions, sensitivity to pain and analgesic response (via morphine or placebo administration) will be assessed using a heat-capsaicin pain model.

This study will be conducted in 2 major parts-3 screening visits (2 outpatient and 1 inpatient) and 2 experimental inpatient visits. Part 1 of the study will involve a 1-week screening period. This will involve two separate screening visits lasting about 2 hours each. At Screening Visit 1, participants will complete questionnaires, an interview, and undergo toxicology screening. At Screening Visit 2, participants will complete questionnaires, undergo a physical exam, and be familiarized with pain testing procedures. At Screening Visit 3, participants will undergo an inpatient sleep study.

Part 2 will involve two different inpatient admissions. The two admissions will be separated by at least two weeks. During each of the admissions, participants' sleep will be studied at night. The first admission will begin immediately following the overnight sleep study in Screening Visit 3. One of the admissions will be for one night and the other admission will be for three nights. For the one night admission, participants will sleep undisturbed for an 8-hour period. For the three night admission, participants will undergo sleep disruption for two nights in a row. On the third night, participants will be allowed to sleep undisturbed for 8 hours for recovery.

During both inpatient admissions, pain testing procedures will be completed that will last approximately 5 hours during the day. During testing, small amounts of blood will be drawn for analysis. Participants will be randomly assigned to two groups. Group A will be given a standard dose of morphine during pain testing. Group B will be given a placebo during pain testing.

Conditions

Sleep Deprivation; Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Morphine US then Morphine FA

Participants randomized to receive Morphine and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.

Group Type: EXPERIMENTAL

Morphine

Intervention Type: DRUG

0.08mg/kg will be administered to participants randomly assigned to receive the drug via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).

Forced Awakenings

Intervention Type: BEHAVIORAL

Participants will be awakened each hour during an 8 hour sleep opportunity period. One of the awakenings is for 60 minutes and randomly determined. The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour. The maximum total sleep time a participant will receive is 280 minutes.

Uninterrupted Sleep

Intervention Type: BEHAVIORAL

Participants will receive an 8 hour period of undisturbed sleep

Placebo US then Placebo FA

Participants randomized to receive the saline placebo and the Uninterrupted Sleep (US) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.

Group Type: PLACEBO_COMPARATOR

Saline Placebo

Intervention Type: DRUG

Saline Placebo will administered to participants randomly assigned to receive the placebo via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).

Forced Awakenings

Intervention Type: BEHAVIORAL

Participants will be awakened each hour during an 8 hour sleep opportunity period. One of the awakenings is for 60 minutes and randomly determined. The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour. The maximum total sleep time a participant will receive is 280 minutes.

Uninterrupted Sleep

Intervention Type: BEHAVIORAL

Participants will receive an 8 hour period of undisturbed sleep

Morphine FA then Morphine US

Participants randomized to receive Morphine and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.

Group Type: EXPERIMENTAL

Morphine

Intervention Type: DRUG

0.08mg/kg will be administered to participants randomly assigned to receive the drug via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).

Forced Awakenings

Intervention Type: BEHAVIORAL

Participants will be awakened each hour during an 8 hour sleep opportunity period. One of the awakenings is for 60 minutes and randomly determined. The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour. The maximum total sleep time a participant will receive is 280 minutes.

Uninterrupted Sleep

Intervention Type: BEHAVIORAL

Participants will receive an 8 hour period of undisturbed sleep

Placebo FA then Placebo US

Participants randomized to receive the saline placebo and the Forced Awakenings (FA) condition first. After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA). With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US). They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.

Group Type: PLACEBO_COMPARATOR

Saline Placebo

Intervention Type: DRUG

Saline Placebo will administered to participants randomly assigned to receive the placebo via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).

Forced Awakenings

Intervention Type: BEHAVIORAL

Participants will be awakened each hour during an 8 hour sleep opportunity period. One of the awakenings is for 60 minutes and randomly determined. The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour. The maximum total sleep time a participant will receive is 280 minutes.

Uninterrupted Sleep

Intervention Type: BEHAVIORAL

Participants will receive an 8 hour period of undisturbed sleep

Interventions

Morphine

0.08mg/kg will be administered to participants randomly assigned to receive the drug via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).

Intervention Type: DRUG

Saline Placebo

Saline Placebo will administered to participants randomly assigned to receive the placebo via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).

Intervention Type: DRUG

Forced Awakenings

Participants will be awakened each hour during an 8 hour sleep opportunity period. One of the awakenings is for 60 minutes and randomly determined. The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour. The maximum total sleep time a participant will receive is 280 minutes.

Intervention Type: BEHAVIORAL

Uninterrupted Sleep

Participants will receive an 8 hour period of undisturbed sleep

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Healthy
• Age 18-48
• Meets Research Diagnostic Criteria for Normal Sleepers
• Stable sleep phase within 21:00 and 08:00
• Total sleep time between 6.5 and 8.5 hours per night
• Sleep efficiency ≥85%
• Epworth Sleepiness Scale Score <10
• Non-smoker/non-nicotine users
• Low Caffeine Users (≤2 cups per day)

Exclusion Criteria

• Body Mass Index ≥35
• Lifetime history of chronic pain (>6 months)
• Acute pain
• Significant medical or psychiatric morbidity within 6 months
• Lifetime history of bipolar disorder, psychotic disorder, serious recurrent major depression, serious post-traumatic stress disorder, or seizure disorder
• Respiratory, hepatic, renal, or cardiac conditions that would contraindicate opioid use
• Lifetime history of alcohol or substance abuse or dependence
• Lifetime history of opioid use >36 doses or >7 days of consecutive use
• Prior adverse reaction to general anesthetics, opioids, or capsaicin
• Clinically significant abnormal complete blood count or comprehensive metabolic profile
• Positive toxicology screen for opioids or recreational drugs
• Pregnant or lactating women
• Significant pre-admission psychological distress (T-scores >64 on the Brief Symptom Inventory Global Scales)
• Significant lifetime history of serious head injury that is determined to influence pain processing or sleep systems

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 48 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Smith, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University Bayview Medical Center

Baltimore, Maryland, United States

Countries

United States

References

Irwin MR, Olmstead R, Bjurstrom MF, Finan PH, Smith MT. Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial. Pain. 2023 May 1;164(5):1128-1137. doi: 10.1097/j.pain.0000000000002811. Epub 2022 Oct 27.

Reference Type: DERIVED

PMID: 36314570 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01DA032922-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00071465

Identifier Type: -

Identifier Source: org_study_id