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Sleep and Inflammatory Resolution Pathway

Primary Purpose

Inflammatory Response, Inflammation, Sleep

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Aspirin
Placebo
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Inflammatory Response

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Control Sleep/Non-Active Placebo or 81mg Aspirin Pill

Sleep Restriction/81mg Aspirin Pill

Sleep Restriction/Non-Active Placebo

Arm Description

Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay

Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay

Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay

Outcomes

Primary Outcome Measures

Inflammatory Resolution Markers
Resolvins

Secondary Outcome Measures

Inflammatory Markers
Interleukin-6

Full Information

First Posted
December 4, 2017
Last Updated
May 9, 2023
Sponsor
Beth Israel Deaconess Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03377543
Brief Title
Sleep and Inflammatory Resolution Pathway
Official Title
Patterns of Sleep Restriction and Recovery: The Inflammatory Resolution Pathways
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 6, 2018 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Response, Inflammation, Sleep, Sleep Restriction

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control Sleep/Non-Active Placebo or 81mg Aspirin Pill
Arm Type
Experimental
Arm Description
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Arm Title
Sleep Restriction/81mg Aspirin Pill
Arm Type
Experimental
Arm Description
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Arm Title
Sleep Restriction/Non-Active Placebo
Arm Type
Experimental
Arm Description
Daily intake of pill at bedtime over 2-week period prior to and during the 11-day in-hospital stay
Intervention Type
Drug
Intervention Name(s)
Aspirin
Other Intervention Name(s)
Non-steroidal anti-inflammatory drug
Intervention Description
81mg aspirin pill daily at bedtime over a 25 day period
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
81mg non-active pill that looks like aspirin
Primary Outcome Measure Information:
Title
Inflammatory Resolution Markers
Description
Resolvins
Time Frame
Change from baseline to sleep restriction, single measure in the morning
Secondary Outcome Measure Information:
Title
Inflammatory Markers
Description
Interleukin-6
Time Frame
Change from baseline to sleep restriction, single measure in the morning

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Monika Haack, PhD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

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Sleep and Inflammatory Resolution Pathway

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