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Effect of Sleep Restriction on Adipose Tissue and Skeletal Muscle Insulin Sensitivity (SLEEP-IN)

Primary Purpose

Sleep Disturbance, Postmenopausal Symptoms, Insulin Sensitivity

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Sleep Restriction
Habitual Sleep
Sponsored by
Pennington Biomedical Research Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Sleep Disturbance

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleAccepts Healthy Volunteers

INCLUSION CRITERIA:

  • Body mass index (BMI) 25-35 kg/m2 (inclusive)
  • Postmenopausal (self-reported absence of menstrual cycle for 1-year)
  • Within 10 years of final menstrual cycle
  • Self-reported nocturnal time in bed of ≥6.5 hours per night (for ≥5 nights during a usual week)
  • Willing to not take naps or engage in moderate-to-vigorous physical activity/exercise during both sleep conditions
  • Willing to consume only the meals provided during both sleep conditions
  • Willing to have adipose tissue and skeletal muscle biopsies
  • Willing to have blood, as well as adipose and muscle tissue stored for future use

EXCLUSION CRITERIA:

  • Unstable weight in the last 3 months [gain or loss ≥5% of body weight]
  • History of clinically diagnosed diabetes or a fasting blood glucose >126 mg/dL
  • History of polycystic ovary syndrome (PCOS)
  • Currently taking antihypertension medication known to affect adipose tissue and skeletal muscle metabolism (e.g., diuretics may be allowed)
  • Chronic use of systemic glucocorticoids
  • Chronic use of atypical antipsychotic or bipolar medications
  • Initiation of antidepressant medication within the last 3 months
  • Previous bariatric surgery (or other surgeries) for obesity or weight loss
  • Chronic use of prescription or 'effective' over-the-counter medications affecting sleep, circadian rhythms, or glucose metabolism †
  • Chronic use of hormone replacement therapy
  • History of clinically diagnosed sleep apnea
  • Shift workers (e.g., individuals awake or working between Midnight and 5AM)
  • Inability to spend 5 nights at Pennington Biomedical
  • Unwilling to eat only the food and drink provided by study staff while in the study
  • Unwilling to maintain a consistent and prescribed sleep schedule while in the study
  • Unwilling to maintain a consistent eating schedule while in the study

Sporadic use of certain medications is fine (however, enrollment will depend on a case-by-case basis). If taking sporadically, women should not be taking the medication for 1-month prior to the first Run-In period.

Sites / Locations

  • Pennington Biomedical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Sleep Restriction

Habitual Sleep

Arm Description

Women will undergo 4 nights of sleep restriction treatment.

Women will undergo 4 nights of habitual sleep treatment.

Outcomes

Primary Outcome Measures

Glucose infusion rate (via 2-step hyperinsulinemic-euglycemic clamp) (in vivo)
Insulin sensitivity by a 2-step hyperinsulinemic euglycemic clamp is performed at the end sleep conditions.

Secondary Outcome Measures

Adipose tissue insulin sensitivity (via free fatty acid area-under-the-curve during the low-dose clamp) (in vivo)
During the low-dose insulin portion of the hyperinsulinemic-euglycemic clamp, free fatty acids will be samples across a 3-hour period to quantify a surrogate measure of adipose tissue insulin sensitivity in vivo.
Insulin-dependent suppression of lipolysis (via ex vivo adipose tissue biopsy analyses)
Release of free fatty acids and glycerol in culture.
Fat oxidation and substrate switching (via ex vivo skeletal muscle biopsy analyses)
Using primary myotubes, fat oxidation and substrate switching will be tested by measuring [1-14C]palmitate oxidation ± varying levels of glucose and pyruvate
Insulin sensitivity (via ex vivo skeletal muscle biopsy analyses)
Myotubes will be incubated ± insulin (100nM) in media containing: [U-14C]-glucose to measure glucose oxidation and glycogen synthesis; [3H]-2-deoxyglucose to assess glucose uptake; or unlabeled DMEM to test insulin signaling (western blot)
Gene expression (via ex vivo skeletal muscle biopsy analyses with RNASeq and RT-PCR)
Genes related to oxphos and circadian clock regulators will be assessed by RNASeq and confirmed with RT-PCR.
Glucose Area-Under-The-Curve (via 2-hour standard meal test)
Glucose area-under-the-curve (AUC) will be calculated throughout a 2-hour period following consumption of a standard meal (dinner shake) test on Day 4 of each sleep condition.
Insulin Area-Under-The-Curve (via 2-hour standard meal test)
Insulin area-under-the-curve (AUC) will be calculated throughout a 2-hour period following consumption of a standard meal (dinner shake) test on Day 4 of each sleep condition.
Blood pressure (via 24-hour ambulatory blood pressure monitoring)
Blood pressure monitoring will be performed for a 24-hour period during Day 3 of each sleep conditions.
Resting metabolic rate (via indirect calorimetry)
O2 consumption and CO2 production will be measured by indirect calorimetry for 40 min (last 30 min will be used for calculations) using a metabolic cart. Resting metabolic rate will be derived using standard equations.

Full Information

First Posted
January 13, 2020
Last Updated
November 11, 2022
Sponsor
Pennington Biomedical Research Center
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1. Study Identification

Unique Protocol Identification Number
NCT04286451
Brief Title
Effect of Sleep Restriction on Adipose Tissue and Skeletal Muscle Insulin Sensitivity
Acronym
SLEEP-IN
Official Title
Effect of Sleep Restriction on Adipose Tissue and Skeletal Muscle Insulin Sensitivity
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
July 28, 2020 (Actual)
Primary Completion Date
April 13, 2022 (Actual)
Study Completion Date
April 13, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Pennington Biomedical Research Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Inadequate sleep is an independent risk factor for metabolic abnormalities (such as obesity, insulin resistance, and hyperglycemia). Women report sleep disruption during the menopause transition (perimenopause) and into the postmenopausal years. Sleep disruption is one of the primary reasons why midlife women seek medical care, with up to 60% reporting significant sleep disturbances (e.g., trouble falling asleep, early morning waking, and hot flashes/night sweats). Despite the majority of women experiencing sleep disruption, no study has investigated the molecular mechanisms linking sleep disruption and the changes in metabolism that coincide with menopause.
Detailed Description
The investigators will conduct a randomized, crossover trial investigating the effect of sleep restriction compared to habitual sleep on adipose tissue and skeletal muscle insulin sensitivity in vivo and ex vivo. The investigators will randomize up to 10 healthy postmenopausal women with overweight/obesity and ≥6.5 hours of self-reported habitual nightly sleep to 4 nights of each sleep condition (sleep restriction and habitual sleep). After the fourth night of each sleep condition, the investigators will administer a two-step hyperinsulinemic-euglycemic clamp and collect skeletal muscle and adipose tissue samples prior to insulin infusion. The overarching hypothesis is that sleep restriction will reduce skeletal muscle and adipose tissue insulin sensitivity compared to habitual sleep.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Disturbance, Postmenopausal Symptoms, Insulin Sensitivity, Cardiovascular Risk Factor

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sleep Restriction
Arm Type
Experimental
Arm Description
Women will undergo 4 nights of sleep restriction treatment.
Arm Title
Habitual Sleep
Arm Type
Experimental
Arm Description
Women will undergo 4 nights of habitual sleep treatment.
Intervention Type
Behavioral
Intervention Name(s)
Sleep Restriction
Intervention Description
Women will be undergo 4 nights of sleep restriction.
Intervention Type
Behavioral
Intervention Name(s)
Habitual Sleep
Intervention Description
Women will be undergo 4 nights of habitual sleep.
Primary Outcome Measure Information:
Title
Glucose infusion rate (via 2-step hyperinsulinemic-euglycemic clamp) (in vivo)
Description
Insulin sensitivity by a 2-step hyperinsulinemic euglycemic clamp is performed at the end sleep conditions.
Time Frame
4 days
Secondary Outcome Measure Information:
Title
Adipose tissue insulin sensitivity (via free fatty acid area-under-the-curve during the low-dose clamp) (in vivo)
Description
During the low-dose insulin portion of the hyperinsulinemic-euglycemic clamp, free fatty acids will be samples across a 3-hour period to quantify a surrogate measure of adipose tissue insulin sensitivity in vivo.
Time Frame
4 days
Title
Insulin-dependent suppression of lipolysis (via ex vivo adipose tissue biopsy analyses)
Description
Release of free fatty acids and glycerol in culture.
Time Frame
4 days
Title
Fat oxidation and substrate switching (via ex vivo skeletal muscle biopsy analyses)
Description
Using primary myotubes, fat oxidation and substrate switching will be tested by measuring [1-14C]palmitate oxidation ± varying levels of glucose and pyruvate
Time Frame
4 days
Title
Insulin sensitivity (via ex vivo skeletal muscle biopsy analyses)
Description
Myotubes will be incubated ± insulin (100nM) in media containing: [U-14C]-glucose to measure glucose oxidation and glycogen synthesis; [3H]-2-deoxyglucose to assess glucose uptake; or unlabeled DMEM to test insulin signaling (western blot)
Time Frame
4 days
Title
Gene expression (via ex vivo skeletal muscle biopsy analyses with RNASeq and RT-PCR)
Description
Genes related to oxphos and circadian clock regulators will be assessed by RNASeq and confirmed with RT-PCR.
Time Frame
4 days
Title
Glucose Area-Under-The-Curve (via 2-hour standard meal test)
Description
Glucose area-under-the-curve (AUC) will be calculated throughout a 2-hour period following consumption of a standard meal (dinner shake) test on Day 4 of each sleep condition.
Time Frame
4 days
Title
Insulin Area-Under-The-Curve (via 2-hour standard meal test)
Description
Insulin area-under-the-curve (AUC) will be calculated throughout a 2-hour period following consumption of a standard meal (dinner shake) test on Day 4 of each sleep condition.
Time Frame
4 days
Title
Blood pressure (via 24-hour ambulatory blood pressure monitoring)
Description
Blood pressure monitoring will be performed for a 24-hour period during Day 3 of each sleep conditions.
Time Frame
24 hours
Title
Resting metabolic rate (via indirect calorimetry)
Description
O2 consumption and CO2 production will be measured by indirect calorimetry for 40 min (last 30 min will be used for calculations) using a metabolic cart. Resting metabolic rate will be derived using standard equations.
Time Frame
4 days

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION CRITERIA: Body mass index (BMI) 25-35 kg/m2 (inclusive) Postmenopausal (self-reported absence of menstrual cycle for 1-year) Within 10 years of final menstrual cycle Self-reported nocturnal time in bed of ≥6.5 hours per night (for ≥5 nights during a usual week) Willing to not take naps or engage in moderate-to-vigorous physical activity/exercise during both sleep conditions Willing to consume only the meals provided during both sleep conditions Willing to have adipose tissue and skeletal muscle biopsies Willing to have blood, as well as adipose and muscle tissue stored for future use EXCLUSION CRITERIA: Unstable weight in the last 3 months [gain or loss ≥5% of body weight] History of clinically diagnosed diabetes or a fasting blood glucose >126 mg/dL History of polycystic ovary syndrome (PCOS) Currently taking antihypertension medication known to affect adipose tissue and skeletal muscle metabolism (e.g., diuretics may be allowed) Chronic use of systemic glucocorticoids Chronic use of atypical antipsychotic or bipolar medications Initiation of antidepressant medication within the last 3 months Previous bariatric surgery (or other surgeries) for obesity or weight loss Chronic use of prescription or 'effective' over-the-counter medications affecting sleep, circadian rhythms, or glucose metabolism † Chronic use of hormone replacement therapy History of clinically diagnosed sleep apnea Shift workers (e.g., individuals awake or working between Midnight and 5AM) Inability to spend 5 nights at Pennington Biomedical Unwilling to eat only the food and drink provided by study staff while in the study Unwilling to maintain a consistent and prescribed sleep schedule while in the study Unwilling to maintain a consistent eating schedule while in the study Sporadic use of certain medications is fine (however, enrollment will depend on a case-by-case basis). If taking sporadically, women should not be taking the medication for 1-month prior to the first Run-In period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kara L Marlatt, PhD, MPH
Organizational Affiliation
Pennington Biomedical Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pennington Biomedical Research Center
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States

12. IPD Sharing Statement

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Effect of Sleep Restriction on Adipose Tissue and Skeletal Muscle Insulin Sensitivity

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