Mechanisms of Sleep Disruption Hyperalgesia (ESP2)

Johns Hopkins University

Status: Completed

Conditions: Sleep Deprivation; Pain

Treatments: Behavioral: Uninterrupted Sleep; Behavioral: Forced Awakenings; Drug: Saline Placebo; Drug: Morphine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01794689

NA_00071465

1R01DA032922-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 18 to 48 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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100 participants in 4 patient groups, including a placebo group

Morphine US then Morphine FA

Experimental group

Description:

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.

Treatment:

Drug: Morphine

Behavioral: Uninterrupted Sleep

Behavioral: Forced Awakenings

Placebo US then Placebo FA

Placebo Comparator group

Description:

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.

Treatment:

Behavioral: Uninterrupted Sleep

Behavioral: Forced Awakenings

Drug: Saline Placebo

Morphine FA then Morphine US

Experimental group

Description:

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.

Treatment:

Drug: Morphine

Behavioral: Uninterrupted Sleep

Behavioral: Forced Awakenings

Placebo FA then Placebo US

Placebo Comparator group

Description:

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.

Treatment:

Behavioral: Uninterrupted Sleep

Behavioral: Forced Awakenings

Drug: Saline Placebo