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Sleep Effectiveness and Insulin and Glucose Homeostasis

Primary Purpose

Diabetes, Prediabetic, Prediabetes

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

eszopiclone

About this trial

This is an interventional treatment trial for Diabetes focused on measuring Diabetes, Prediabetic, Prediabetes, Glucose intolerance, Sleep quality, Continuous glucose monitoring, Diabetes risk, eszopiclone

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy volunteers, men and women 18-64 years of age.
Fluent English speakers.
Health status as per criteria listed for prediabetes and diabetes (based on 2003 American Diabetes Association criteria and 2009 International Expert Committee Report: Prediabetics will have impaired glucose tolerance with fasting plasma glucose (FPG) 100-125 mg/dL, Hemoglobin A1C 5.7-6.4%, or 2-hour plasma glucose (PG) 140-199 mg/dL after 75-g oral glucose tolerance test (OGTT). Diabetics will have FPG ≥ 126 mg/dL, Hemoglobin A1C ≥ 6.5%, or 2-hour PG ≥ 200 mg/dL on OGTT.

Exclusion Criteria:

Primary psychiatric disease or conditions which may independently contribute to sleep fragmentation or may hinder the subject's ability to complete the proposed testing:
Respiratory, liver, or clotting disorders
History of sleep disordered breathing, Restless legs syndrome or Periodic limb movement disorder or high clinical suspicion of sleep disordered breathing or other sleep disorder (e.g., snoring, excessive daytime sleepiness, frequent napping, excessive motor activity)
Shift worker or circadian phase disorder
Abnormal resting ECG, pacemaker, atrial fibrillation or other arrhythmia
Seizure disorder
History of depression, bipolar disorder, anxiety disorder, schizophrenia or use of psychiatric medication
Narcolepsy
Tobacco or recreational drug use
Pregnancy or lactation
Regular use of stimulants or hypnotic medication
Evidence of sleep apnea (Apnea-Hypopnea Index > 10 on screening sleep study)

Sites / Locations

Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

eszopiclone

Arm Description

We will evaluate the impact of pharmacologic enhancement of effective sleep with nightly eszopiclone (taken before bedtime for 1 week, home environment) on glycemic profiles (continuous glucose monitoring, 72 hrs) in prediabetics and diabetics compared to pretreatment baseline. The dose of eszopiclone will be the lowest tolerated dose (1-3 mg) via dose escalation and side effect profile assessment.

Outcomes

Primary Outcome Measures

change in continuous glucose profile

continuous glucose monitoring (CGM) results - mean daytime, post prandial and nocturnal glucose between baseline and after 1 week of eszopiclone

Secondary Outcome Measures

change in Sleep effectiveness biomarkers

M1 results - percentage of high frequency coupling at baseline compared to after 7 nights eszopiclone

Full Information

NCT ID

NCT01887691

First Posted

June 24, 2013

Last Updated

December 18, 2019

Sponsor

Beth Israel Deaconess Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01887691

Brief Title

Sleep Effectiveness and Insulin and Glucose Homeostasis

Official Title

Sleep Effectiveness and Insulin and Glucose Homeostasis

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Terminated

Study Start Date

October 2012 (undefined)

Primary Completion Date

August 2015 (Actual)

Study Completion Date

December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Beth Israel Deaconess Medical Center

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to examine the influence of sleep effectiveness on glucose and insulin metabolism in health and disease (prediabetes and type two diabetes). We will monitor sleep effectiveness using the sleep spectrogram, obtain serial nocturnal blood glucose and insulin measurements, and assess the impact of pharmacologic enhancement [using eszopiclone (Lunesta), a medication that promotes stable sleep)] on glucose and insulin homeostasis. We hypothesize that 1: Effective sleep is associated with enhanced insulin sensitivity, relative to ineffective sleep states, and 2: Enhancing sleep effectiveness using eszopiclone (Lunesta) improves 24-hour glucose metabolism in prediabetics and diabetics compared to baseline.

Detailed Description

Evidence from experimental studies supports the hypothesis that fragmented or insufficient sleep contributes to impaired glucose and insulin homeostasis. The sleep spectrogram, an EEG-independent measure of sleep effectiveness, maps coupled oscillations of heart rate variability and ECG-derived respiration. In a sample of non-diabetic subjects with and without sleep apnea, we previously explored the association between ECG-spectrogram derived biomarkers and glucose metabolism and found that the marker of effective sleep, High Frequency Coupling (HFC), is associated with reduced diabetes risk (increased Disposition Index). HFC is also enhanced by sedative medications (unpublished data). In this study we will 1.) explore the relationship between sleep effectiveness and insulin sensitivity across the sleep period, by frequently sampling glucose and insulin during nocturnal polysomnography in healthy and prediabetic subjects; and 2.) evaluate the impact of pharmacologic enhancement of effective sleep with nightly eszopiclone (1 week, home environment) on glycemic profiles (continuous glucose monitoring, 72 hrs) in prediabetics and diabetics compared to pretreatment baseline. We expect that desirable glycemic profiles will correlate with the spectrographic marker of effective sleep while undesirable glucose profiles will correlate with the marker of ineffective sleep. Using pharmacologic enhancement of effective sleep, we expect to demonstrate improvement in glycemic profiles in prediabetic and diabetic subjects compared to pre-treatment baseline.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes, Prediabetic, Prediabetes, Glucose Intolerance

Keywords

Diabetes, Prediabetic, Prediabetes, Glucose intolerance, Sleep quality, Continuous glucose monitoring, Diabetes risk, eszopiclone

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

eszopiclone

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

eszopiclone

Other Intervention Name(s)

Lunesta

Intervention Description

Eszopiclone at a dose of 1-3 mg (lowest tolerated dose, as determined using a dose escalation schedule and side effect profile)will be taken 30 minutes before bedtime for one week.

Primary Outcome Measure Information:

Title

change in continuous glucose profile

Description

continuous glucose monitoring (CGM) results - mean daytime, post prandial and nocturnal glucose between baseline and after 1 week of eszopiclone

Time Frame

comparing 72 hours of baseline and after 1 week of eszopiclone

Secondary Outcome Measure Information:

Title

change in Sleep effectiveness biomarkers

Description

M1 results - percentage of high frequency coupling at baseline compared to after 7 nights eszopiclone

Time Frame

nightly comparing baseline with post-7 nights of eszopiclone

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy volunteers, men and women 18-64 years of age. Fluent English speakers. Health status as per criteria listed for prediabetes and diabetes (based on 2003 American Diabetes Association criteria and 2009 International Expert Committee Report: Prediabetics will have impaired glucose tolerance with fasting plasma glucose (FPG) 100-125 mg/dL, Hemoglobin A1C 5.7-6.4%, or 2-hour plasma glucose (PG) 140-199 mg/dL after 75-g oral glucose tolerance test (OGTT). Diabetics will have FPG ≥ 126 mg/dL, Hemoglobin A1C ≥ 6.5%, or 2-hour PG ≥ 200 mg/dL on OGTT. Exclusion Criteria: Primary psychiatric disease or conditions which may independently contribute to sleep fragmentation or may hinder the subject's ability to complete the proposed testing: Respiratory, liver, or clotting disorders History of sleep disordered breathing, Restless legs syndrome or Periodic limb movement disorder or high clinical suspicion of sleep disordered breathing or other sleep disorder (e.g., snoring, excessive daytime sleepiness, frequent napping, excessive motor activity) Shift worker or circadian phase disorder Abnormal resting ECG, pacemaker, atrial fibrillation or other arrhythmia Seizure disorder History of depression, bipolar disorder, anxiety disorder, schizophrenia or use of psychiatric medication Narcolepsy Tobacco or recreational drug use Pregnancy or lactation Regular use of stimulants or hypnotic medication Evidence of sleep apnea (Apnea-Hypopnea Index > 10 on screening sleep study)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Melanie Pogach, MD

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

Citations:

PubMed Identifier

22215928

Citation

Pogach MS, Punjabi NM, Thomas N, Thomas RJ. Electrocardiogram-based sleep spectrogram measures of sleep stability and glucose disposal in sleep disordered breathing. Sleep. 2012 Jan 1;35(1):139-48. doi: 10.5665/sleep.1604.

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Sleep Effectiveness and Insulin and Glucose Homeostasis

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