Sleep Effectiveness and Insulin and Glucose Homeostasis

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes; Glucose Intolerance; Prediabetes; Prediabetic
• Intervention / Treatment: Drug: eszopiclone

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 HFC is also enhanced by sedative medications (unpublished data).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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: eszopiclone; 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.

Drug: eszopiclone; 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.; Other Names: Lunesta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	comparing 72 hours of baseline and after 1 week of eszopiclone

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in Sleep effectiveness biomarkers	M1 results - percentage of high frequency coupling at baseline compared to after 7 nights eszopiclone	nightly comparing baseline with post-7 nights of eszopiclone

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Melanie Pogach, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: June 24, 2013
• First Submitted That Met QC Criteria: June 25, 2013
• First Posted (Estimate): June 27, 2013

Study Record Updates

• Last Update Posted (Actual): December 19, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes; Prediabetes; Glucose intolerance; Sleep quality; Continuous glucose monitoring; Prediabetic; Diabetes risk; eszopiclone
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Eszopiclone
• Other Study ID Numbers: 2012P000187

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No