Ketogenic Diet Treatment of Obesity With Co-morbid Type 2 Diabetes Mellitus and/or Obstructive Sleep Apnea

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and safety of ketogenic diet (KD) treatment of (i) obesity, (ii) type 2 diabetes mellitus and (iii) obstructive sleep apnea (OSA) in patients with obesity and Type 2 DM and in patients with obesity and/or OSA. This will be a randomized, open-label three arm controlled study comparing weight loss in obese participants with type 2 diabetes and/or obstructive sleep apnea treated for 9 months with 3:1 [fat]:[protein+carbohydrate] ratio, 1600 kcal/day diet (Group A) with weight loss in participants treated with orlistat 120 mg TID and lifestyle intervention consisting of dietary advice, recommended caloric goal of 1600 kcal/day (Group B), and in participants treated with only lifestyle intervention consisting of dietary advice, recommended caloric goal of 1600 kcal/day (Group C).

Detailed Description
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The study sample will be randomized into three treatment arms, KD (Group A, n=50), Orlistat 120 mg TID (Group B, n=50) and dietary and lifestyle counseling (Group C, n=50) in a 1:1:1 ratio. Each arm will include 100% participants with obesity and co-morbid type 2 DM and 50% participants with co-morbid OSA. Randomization will be stratified for diabetic status.

Official Title
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Evaluation of Efficacy and Safety of Ketogenic Diet Treatment of Obesity With Co-morbid Type 2 Diabetes Mellitus and/or Obstructive Sleep Apnea.

Conditions
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Obesity, Diabetes, Obstructive Sleep Apnea

Intervention / Treatment
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* Other: Ketogenic diet
* Drug: Orlistat
* Other: Standardized diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-70 ability and willingness to signed informed consent form BMI more than 30kg/m2, with type 2 DM and/or OSA For diabetic participants, stable hypoglycemic medications for at least 2 months For participants with OSA, previously documented polysomnogram with apnea/hypopnea index (AHI)>15/h. Exclusion Criteria: BMI change of +/- 3.0 kg/m2 of baseline BMI within past 12 months. History of bariatric surgery ≤ 3 years prior to enrollment. Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, unstable metabolic or endocrine disturbances, renal or liver disease, past history of renal calculi, hyperuricemia, hypercalcemia, mitochondrial disease, known disorder of fatty acid metabolism, porphyria, and active systemic cancer. History of uncontrolled hyperlipidemia For participants with DM, change in the dose or type of hypoglycemic treatment within 2 months prior to enrollment. Psychosis within six months of enrollment, evidenced by treatment with anti-psychotic medications with recent medication initiation or dose increase. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements; History of hyperthyroidism History of glaucoma History of cerebrovascular disease or unstable heart disease within 6 months of enrollment Pregnancy Use of any investigational drugs within 3 months of enrollment. Inability or unwillingness of subject to give written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ketogenic diet, lifestyle counseling<br>ketogenic diet consisted of 3:1[fat]:[protein+carbohydrate] weight ratio with 1600kcal restriction. | Other: Ketogenic diet<br>* ketogenic diet will consist of 3:1[fat]:[protein+carbohydrate]weight ratio with 1600 kcal restriction. Diet will last 9 months.<br>* Other names: high fat, low protein, low carbohydrate diet;|
| Active Comparator: Orlistat, Lifestyle counseling<br>Orlistat 120 mg TID, standardized diet and lifestyle-modification counseling based on the LEARN (Life, Exercise, Attitudes, Relationships,and Nutrition) program with recommended caloric goal of 1600 kcal/day. | Drug: Orlistat<br>* Orlistat 120 mg TID for 9 months; life style intervention with recommended caloric goal of 1600 kcal/day.<br>* Other names: tetrahydrolipstatin;|
| Active Comparator: Standartized diet, Lifestyle counseling<br>Standardized diet and lifestyle-modification counseling based on the LEARN (Lifestyle, Exercise, Attitudes, Relationship, Nutrition) program with recommended caloric goal of 1600kcal/day. | Other: Standardized diet<br>* Standardized diet treatment for 9 months with recommended caloric goal of 1600kcal/day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of body mass index from baseline in 9 months period | The change of weight and the BMI(body mass index) will be calculated. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in glucose blood level in patients with diabetes mellitus in 9 months. | HbA1C, fasting serum glucose insulin and leptin levels and fasting lipid levels | 9 months | 
| Change of apnea/hypopnea index in patients with obstructive sleep apnea in patients with obesity | For participants with OSA, secondary outcome will include polysomnogram-derived apnea/hypopnea index. Level of alertness will be evaluated with Epworth Sleepiness Scale. | 9 months | 
| To evaluate safety of ketogenic diet as a treatment of obesity. | Evaluate in serum levels of beta-hydroxybutyrate, glucose, electrolytes, renal and liver functions, uric acid, HbA1C, serum lipid profile, insulin and leptin levels, CRP. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketogenic diet, obesity, diabetes, obstructive sleep apnea