Effects of Treatment of Sleep Apnea on Metabolic Syndrome

A Controlled Trial of Continuous Positive Airway Pressure (CPAP) Therapy on Metabolic Control in Individuals With Impaired Glucose Tolerance and Sleep Apnea

The investigators performed a randomized, cross-over controlled clinical trial comparing 8 weeks of Continuous Positive Airway Pressure (CPAP) to 8 weeks of sham-CPAP in patients with moderate to severe Sleep Disordered Breathing (SDB) and impaired glucose tolerance. A rigorous assessment of metabolic responses to SDB treatment in this group is of great clinical significance because this sample is at high risk for developing diabetes. The paradigm shift of CPAP as a mode of prevention can affect clinical practice in the fields of both primary care and sleep medicine.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea; Impaired Glucose Tolerance
• Intervention / Treatment: Device: Continuous Positive Airway Pressure (CPAP) (Philips-Respironics RemStar Pro® CPAP); Device: Sham-Continuous Positive Airway Pressure (CPAP) (Philips-Respironics)

Detailed Description

There are few controlled studies that address whether treatment of sleep apnea improves glucose tolerance. This is a randomized, double-blind cross-over study of subjects with sleep apnea (apnea hypopnea index > 15) and impaired glucose tolerance. Subjects will be randomized to 8 weeks of Continuous Positive Airway Pressure (CPAP) or sham-CPAP, followed by the alternate therapy after a one month wash-out. After each treatment, subjects will undergo 2-hour oral glucose tolerance testing, polysomnography, actigraphy, and measurements of indices of glucose control. The investigators intend to analyze the changes in glucose metabolism and insulin sensitivity in patients with sleep apnea with CPAP intervention.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• moderate to severe Sleep Disordered Breathing (SDB) defined by an Apnea Hypopnea Index (AHI) > 15
• had evidence of Impaired Glucose Tolerance (IGT) defined by the mean 2-hour Oral Glucose Tolerance Test (OGTT) glucose of > 140 mg/dl calculated from the two 2-hour OGTTs performed within 3 days of each other

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continuous Positive Airway Pressure (CPAP)	Device: Continuous Positive Airway Pressure (CPAP) (Philips-Respironics RemStar Pro® CPAP); Subjects will be randomized to 8 weeks of CPAP or sham-CPAP, followed by the alternate therapy after a one month wash-out.; Other Names: Philips-Respironics RemStar Pro® CPAP
Sham Comparator: Sham-Continuous Positive Airway Pressure (CPAP)	Device: Sham-Continuous Positive Airway Pressure (CPAP) (Philips-Respironics); Subjects will be randomized to 8 weeks of CPAP or sham-CPAP, followed by the alternate therapy after a one month wash-out.; Other Names: Philips-Respironics Sham CPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Normalization of Impaired Glucose Tolerance (IGT)	Number of subjects who experienced normalization of the mean 2-hour oral glucose tolerance test (OGTT) in the overall sample undergoing therapeutic CPAP vs. sham CPAP. (2-hour OGTT glucose< 140 mg/dL)	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean and Standard Deviation of Glucose Indices After Therapeutic CPAP vs. Sham	Reported values include: fasting glucose (mg/dL), 2 hour Oral Glucose Tolerance Test (OGTT) (mg/dL)	20 weeks
Mean and Standard Deviation of Insulin Indices After Therapeutic CPAP vs. Sham	The data for fasting and 2 hour Insulin (iIU/dL) are presented according to therapeutic CPAP vs. Sham CPAP.	20 weeks
Mean and Standard Deviation of Indices of Insulin Resistance With Therapeutic CPAP vs. Sham	Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) with therapeutic CPAP vs. Sham CPAP	20 weeks
Mean and Standard Deviation of Insulin Sensitivity Index (ISI(0,120)) With Therapeutic CPAP vs. Sham	Insulin Sensitivity Index derived from the Gutt Index, uses the plasma glucose and insulin concentration from fasting (0 min) and 120-min samples from the OGTT, to calculate (Metabolic Clearance Rate)/log (Mean Serum Insulin). The range of possible values is based on the subset ranges of fasting and oral glucose tolerance test (OGTT) insulin and fasting and OGTT glucose, which calculate to be a range of 1.6 to 206.8. An increase in the ISI (0,120) indicates an improvement in the insulin sensitivity.	20 Weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Beth Israel Deaconess Medical Center; National Institutes of Health (NIH); National Center for Research Resources (NCRR); Case Western Reserve University
• Investigators: Study Director: Susan Redline, M.D., M.P.H., Brigham and Women's Hospital; Principal Investigator: Faramarz Beigi, Case Western Reserve University; Principal Investigator: H Lester Kirchner, PhD, Case Western Reserve University; Principal Investigator: Carol Rosen, M.D., Case Western Reserve University; Principal Investigator: John Haaga, M.D., Case Western Reserve University; Principal Investigator: Kingman Strohl, M.D., Case Western Reserve University; Principal Investigator: Reena Mehra, M.S., M.S., Case Western Reserve University; Principal Investigator: Denise Babineau, PhD, Case Western Reserve University; Principal Investigator: Tanya Weinstock, M.D., Brigham and Women's Hospital

Publications and helpful links

General Publications

• Weinstock TG, Wang X, Rueschman M, Ismail-Beigi F, Aylor J, Babineau DC, Mehra R, Redline S. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. Sleep. 2012 May 1;35(5):617-625B. doi: 10.5665/sleep.1816.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: June 29, 2011
• First Posted (Estimate): June 30, 2011

Study Record Updates

• Last Update Posted (Estimate): March 12, 2014
• Last Update Submitted That Met QC Criteria: February 10, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Hyperglycemia; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Glucose Intolerance
• Other Study ID Numbers: HL075077; UL1RR024989 (U.S. NIH Grant/Contract)