Sleep Effectiveness and Insulin and Glucose Homeostasis

NCT ID: NCT01887691

Last Updated: 2019-12-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2019-12-31

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 HFC is also enhanced by sedative medications (unpublished data).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

Conditions

Diabetes; Prediabetic; Prediabetes; Glucose Intolerance

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

eszopiclone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Lunesta

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Melanie Pogach, MD, MMSc

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Melanie Pogach, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22215928 (View on PubMed)

Other Identifiers

2012P000187

Identifier Type: -

Identifier Source: org_study_id