Sleep Effectiveness and Insulin and Glucose Homeostasis

Sponsor

Beth Israel Deaconess Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT01887691

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Prediabetic Prediabetes Glucose Intolerance	Drug: eszopiclone	Phase 1

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 HFC is also enhanced by sedative medications (unpublished data).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

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Sleep Effectiveness and Insulin and Glucose Homeostasis

Study Start Date :

Oct 1, 2012

Actual Primary Completion Date :

Aug 1, 2015

Actual Study Completion Date :

Dec 1, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

change in continuous glucose profile [comparing 72 hours of baseline and after 1 week of eszopiclone]
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 [nightly comparing baseline with post-7 nights of eszopiclone]
M1 results - percentage of high frequency coupling at baseline compared to after 7 nights eszopiclone

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)