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Sleep and Inflammatory Resolution Pathway

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ClinicalTrials.gov Identifier: NCT03377543
Recruitment Status : Recruiting
First Posted : December 19, 2017
Last Update Posted : January 30, 2019
Sponsor:
Information provided by (Responsible Party):
Monika Haack, Beth Israel Deaconess Medical Center

Brief Summary:
Goal of this project is to investigate whether increases in inflammation that result from common patterns of restricting sleep on week nights and catching up on sleep over the weekend are caused by disruption in the newly discovered inflammatory resolution pathways. These pathways are crucial in the active termination of the inflammatory response, and their disruption may contribute to ongoing unresolved inflammation, which has been observed not only during periods of sleep restriction, but also after recovery sleep has been obtained. If the hypothesis is true, it is possible that increasing the body's natural production of endogenous, inflammatory resolution mediators may provide a non-behavioral strategy to limit the inflammatory consequences in those undergoing periods of sleep restriction with intermittent recovery sleep.

Condition or disease Intervention/treatment Phase
Inflammatory Response Inflammation Sleep Sleep Restriction Drug: Aspirin Drug: Placebo Early Phase 1

Detailed Description:

Low-grade or unresolved inflammation is involved in the pathogenesis of many human diseases. Common sleep patterns of restricting sleep during the work week and "catching up" on sleep over the weekend lead to inflammatory upregulation that does not recover completely after the weekend.

The goal of this proposal is to investigate, for the first time, inflammatory resolution pathways. Inflammatory resolution mediators, such as resolvins, are derived from omega-3 free fatty acids and actively 'turn-off' inflammation. Based on preliminary data, the investigators hypothesize that common sleep restriction-recovery patterns disrupt inflammatory resolution pathways, making it difficult to return to inflammatory homeostasis. If true, pharmacologically increasing the body's natural production of endogenous inflammatory resolution mediators may provide a way to reduce the detrimental inflammatory consequences of common sleep restriction-recovery patterns.

The hypothesis will be tested using an experimental model that mimics common patterns of restricting sleep on weekdays and "catching up" on sleep on the weekend. The proposal will further utilize the unique ability of low-dose aspirin, which - like no other non-steroidal anti-inflammatory drug - is able to activate inflammatory resolution pathways. Healthy women and men between the ages of 18 to 65 years will be tested under three, 11-day in-hospital stays, during which participants will be exposed to control sleep or common patterns of sleep restriction-recovery. The three in-hospital stays will be combined with preemptive administration of low-dose aspirin or a placebo.

Targeting inflammatory resolution pathways could provide a novel, non-behavioral strategy to mitigate both inflammatory consequences and future disease risks in those undergoing periods of sleep restriction-recovery patterns - a behavior pattern that is unlikely to be eradicated in the near future, as changes in sleep are generally difficult to make and to maintain.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Patterns of Sleep Restriction and Recovery: The Inflammatory Resolution Pathways
Actual Study Start Date : June 6, 2018
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : April 1, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Experimental: Control Sleep/Non-Active Placebo or 81mg Aspirin Pill
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Drug: Aspirin
81mg aspirin pill daily at bedtime over a 25 day period
Other Name: Non-steroidal anti-inflammatory drug

Drug: Placebo
81mg non-active pill that looks like aspirin

Experimental: Sleep Restriction/81mg Aspirin Pill
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Drug: Aspirin
81mg aspirin pill daily at bedtime over a 25 day period
Other Name: Non-steroidal anti-inflammatory drug

Experimental: Sleep Restriction/Non-Active Placebo
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Drug: Placebo
81mg non-active pill that looks like aspirin




Primary Outcome Measures :
  1. Inflammatory Resolution Markers [ Time Frame: Change from baseline to sleep restriction, single measure in the morning ]
    Resolvins


Secondary Outcome Measures :
  1. Inflammatory Markers [ Time Frame: Change from baseline to sleep restriction, single measure in the morning ]
    Interleukin-6



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women and men between the ages 18-65 years.
  • Body mass index (BMI) between 18.5 and 35 kg/m2.
  • For female participants: No significant discomfort during pre-menses/menses.
  • Daily sleep duration between 7-9 hours, verified by electronic sleep diary data for two weeks.
  • Habitual sleep period must begin within one hour of 11:00pm (to ensure normal entrainment).
  • Negative toxicology screen, including: amphetamines, barbiturates, benzodiazepines, cocaine, opiates, and methadone. Toxicology screening will be performed as part of the screening lab tests; an outside lab toxicology screening will not suffice.

Exclusion Criteria:

  • Active infection/disease.
  • Following blood chemistry values outside of the laboratory's normal range or the range specified below:

    • WBC (range: 2.0-10.0 K/uL)
    • Platelet count
    • Hematocrit in range
    • TSH outside of the laboratory's normal range
    • Bilirubin >1.5 upper limit of normal
    • ALT or AST >2.5 upper limit of normal
  • Stage 4 chronic kidney disease based on CKD epi-equation
  • Pre-diabetes or diabetes (HbA1c >5.7%)
  • History of neurological, chronic pain, immune/inflammatory, vascular/cardiovascular (including Raynaud syndrome), liver/kidney, metabolic disorders (including diabetes).
  • Current asthma (diagnosis of asthma and either asthma symptoms present within the past years or taking medication for asthma) and/or history of ASA induced sensitivity
  • Systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90 mmHg prior to the initial and medical screens. Systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg during admissions (Stays 1, 2, and 3)
  • History of gastrointestinal disorders, including esophageal reflux, gastric and duodenal ulcers, gastrointestinal bleeding.
  • Personal or family (first degree relative) history of any stroke
  • History of psychiatric disorders, including major depressive disorders, bipolar disorders, panic disorders, post-traumatic stress disorders (PTSD), thought disorders, and substance abuse/dependence disorders.
  • History of intolerance or allergy to non-steroidal anti-inflammatory drugs (NSAID).
  • Sleep disorders: Sleep efficiency <80% based on polysomnographic (PSG) screening night; respiratory disturbance index of >10 events/hour based on PSG screening night, periodic leg movement index (PLMI) of >25/hour and/or PLMAI (PLM arousal index) of >5/hour based on PSG screening night; restless legs syndrome, circadian rhythm disorders, and nightmare disorders determined by diagnostic interview.
  • Pregnant/nursing.
  • Regular medication use other than oral contraceptives.
  • Intake of non-steroidal anti-inflammatory drugs (NSAIDs) or cold/cough remedies within the last month.
  • Intake of dietary supplements containing DHA/EPA-derived fatty acids (e.g., fish oil) within the last 3 months prior to study start.
  • Donation of blood or platelets within three months prior to or in-between study arms.
  • Smoking.

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): NCT03377543


Contacts
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Contact: Monika Haack, PhD 617 667 5234 mhaack@bidmc.harvard.edu
Contact: Jennifer Scott-Sutherland, M.S. jscottsu@bidmc.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Scott Lamm       Sleeprecovery@bidmc.harvard.edu   
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
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Principal Investigator: Monika Haack, PhD Beth Israel Deaconess Medical Center

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Responsible Party: Monika Haack, Assistant Professor of Neurology, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT03377543     History of Changes
Other Study ID Numbers: 2017P000484
First Posted: December 19, 2017    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Inflammation
Pathologic Processes
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics