Mechanisms of Sleep Disruption Hyperalgesia
ESP2
2 other identifiers
interventional
100
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started May 2013
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 15, 2013
CompletedFirst Posted
Study publicly available on registry
February 20, 2013
CompletedStudy Start
First participant enrolled
May 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2018
CompletedResults Posted
Study results publicly available
February 22, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
March 12, 2019
CompletedAugust 2, 2019
August 1, 2019
4.7 years
February 15, 2013
January 31, 2019
August 1, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings
The area of secondary hyperalgesia (2HA) to mechanical stimulation was quantified by stimulating along eight linear paths near the capsaicin treated site using a 15 gram nonpainful von Frey filament. Stimulation occurred until the participant reported a change in sensation from which a border was marked on the skin. The degree of 2HA was assessed by measuring the total surface area (mm\^2) of the marked borders. Data were collapsed by group to analyze the effects of FA vs US, irrespective of randomization group. Our Primary Secondary Hyperalgesia outcome was measured prior to injection of either morphine or placebo.
Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep
Secondary Outcomes (2)
Opioid Analgesia as Assessed by Analgesia Index (Seconds)
Next day after 2 nights of forced awakenings or uninterrupted sleep
Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation
Next day after 2 nights of forced awakenings or uninterrupted sleep, every 60 minutes up to 7 hours
Other Outcomes (1)
Total Sleep Time
Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep.
Study Arms (4)
Morphine US then Morphine FA
EXPERIMENTALParticipants 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.
Placebo US then Placebo FA
PLACEBO COMPARATORParticipants 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.
Morphine FA then Morphine US
EXPERIMENTALParticipants 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.
Placebo FA then Placebo US
PLACEBO COMPARATORParticipants 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.
Interventions
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).
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).
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.
Participants will receive an 8 hour period of undisturbed sleep
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Johns Hopkins Universitylead
- National Institute on Drug Abuse (NIDA)collaborator
Study Sites (1)
Johns Hopkins University Bayview Medical Center
Baltimore, Maryland, 21224, United States
Related Publications (1)
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.
PMID: 36314570DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Participants were mostly young adults, were generally healthy, pain free and good sleepers. Strict inclusion/exclusion criteria and high participant burden (laboratory pain testing, overnight sleep studies) impacted sample size and study completion.
Results Point of Contact
- Title
- Dr. Michael T. Smith, PhD
- Organization
- Johns Hopkins University
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Smith, Ph.D
Johns Hopkins University
Publication Agreements
- PI is Sponsor Employee
- Yes
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 15, 2013
First Posted
February 20, 2013
Study Start
May 1, 2013
Primary Completion
January 1, 2018
Study Completion
March 12, 2019
Last Updated
August 2, 2019
Results First Posted
February 22, 2019
Record last verified: 2019-08