Effect of Orlistat in Body Composition

Study Overview
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Brief Summary
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The purpose of this study is to determine if a 24 week weight loss program with orlistat 60 mg will produce greater changes in body composition compared to placebo.

Detailed Description
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Large amounts of VAT (adipose tissue surrounding the viscera of the organs), is known to be associated with increased risk of heart disease and diabetes. Orlistat (tetrahydrolipstatin or THL) inhibits gastrointestinal lipase and reduces the absorption of dietary fat. The purpose of this study is to to determine if a 24 week weight loss program with orlistat 60 mg would produce greater changes in adipose tissue depots (specifically VAT) compared to placebo. This study will use the Echo MRI technology across multiple sites to measure total fat mass. EchoMRI is a non invasive method ideally suited for studies which track changes in human body composition over time, with measuring times of less than 3 minutes and no radiation exposure.

Official Title
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The Effects of Weight Reduction With Orlistat vs. Placebo on Changes in Body Composition

Conditions
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Obesity, Overweight

Intervention / Treatment
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* Drug: Orlistat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-60 years inclusive Body Mass Index (BMI): BMI in the range of 25.0-34.9 kg/m^2 Waist circumference: Females: > 35 inches Males: > 40 inches Diet: Normal eating habits, consuming 3 meals a day (breakfast, lunch and dinner) Willing to follow a hypocaloric diet during the study to achieve weight loss Willing to take a daily multivitamin for the duration of the study. General Health:Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or physical examination Exclusion Criteria: Pregnant and/ or Breast-feeding women Diet/Exercise:Currently on a special diet or who cannot fulfill the dietary requirements of the study. Smoking History:a) Smoking cessation within the past 6 months b) Current Smokers Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials and study foods (or closely related compounds) or any of their stated ingredients. Medication: a) Currently taking medication for weight loss or appetite control. b) Previous Xenical® (orlistat) or alli® use within 3 months of screening date c) Currently taking medication or supplements that influence intestinal transit time and other stool formation parameters or influences cramping (e.g., Anticholinergics (such as atropine) or cholinergics (such as physostigmine), phenothiazines, tricyclic antidepressants, opioid analgesics (including loperamide), calcium channel antagonists, clonidine, cisapride, octreotide. Also, any laxative or antidiarrheal product). d) Currently taking or withdrawn during the past 6 months any drugs with significant impact on body weight (e.g. serotoninergically acting drugs, antidepressants, central adrenergically acting drugs, drugs inhibiting digestion and absorption, appetite suppressants, metformin) e) Currently taking Cyclosporine, Warfarin or Amiodarone HCL Disease/Surgery: a) History of gastrointestinal disease (e.g., irritable bowel syndrome, diarrhea, inflamed bowel, steatorrhea/fat malabsorption, hemorrhoids, incontinence, pancreatitis). b) History of psychological disorder, including eating disorders such as anorexia nervosa and bulimia c) History of neurological disorder (e.g. seizures, parkinson's disease, Alzheimer's disease) d) History of hypo/hyperthyroidism unless euthyroid and controlled on a stable dose of medication for at least 6 months. e) History of surgery for weight loss f) Uncontrolled hypertension g) Heart Disease h) Diabetes Mellitus (Type 1 and 2) (Fasting Blood Glucose >126 mg/dL) Participant has a known history of panic attacks and/or claustrophobia or other conditions precluding safe EchoMRI, CT or other scanning modalities according to local guidelines, (e.g., pacemaker, hearing aid, metallic body piercing and/or other metal implants) or in the opinion of the Investigator the participant exceeds size limitations for the instruments. Participant has had a weight loss or gain of greater than or equal to 3 kg in the 3 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Orlistat<br>Orlistat 60 milligram (mg) capsules to be consumed orally with each meal 3 times per day | Drug: Orlistat<br>* Weight loss treatment<br>|
| Placebo Comparator: Placebo<br>Placebo to match Orlistat 60 mg capsules to be consumed orally with each meal 3 times per day. | Drug: Placebo<br>* Inactive<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in Abdominal VAT Mass | VAT was measured by the computed tomography (CT) scan. | Baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in Abdominal VAT Mass | Abdominal VAT mass from baseline to week 12 was measured by CT scan. | Baseline to week 12 | 
| Change From Baseline to Week 24 in Body Weight | Participants were weighed at least twice until two consecutive measurements were within 0.5 kg of each other and the average of the two measurements was recorded. | Baseline to week 24 | 
| Change From Baseline to Week 24 in Total Fat Mass | Change in total fat mass was calculated from an average of three measurements at each visit from Echo Magnetic Resonance Imaging (EchoMRI). | Baseline to week 24 | 
| Change From Baseline to Week 24 in Percentage Body Fat | Body fat was assessed through Bioelectrical Impedance Analysis (BIA). | Baseline to week 24 | 
| Change From Baseline to Week 24 in Waist Circumference | Waist circumference was measured against the skin, without interference from clothing, at the level midway between the lateral lower rib margin and the iliac crest in standing position. | Baseline to week 24 | 
| Change From Baseline to Week 24 in Percentage Liver Fat | For Liver fat, Intrahepatic lipids (IHL) were measured by Magnetic Resonance Spectroscopy (MRS). | Baseline to week 24 | 
| Change From Baseline to Week 24 in Liver Fat | The liver fat was measured by CT scan in Hounsfield Units (HU). | Baseline to week 24 | 
| Change From Baseline to Week 24 in Total Calories Expended for Physical Activity | Measurement of physical activity from Paffenbarger questionnaire. The number of caloried expended was representation of activity level: Higher calorie counts indicate higher activity | Baseline to week 24 | 
| Change From Baseline to Week 24 in Quality of Life (QoL) Scores. | QoL scores were measured using an Impact of Weight Quality of Life (IWQoL) Questionnaire, which scored the responses at a scale of 1 to 5(1, never true, to 5, always true): QoL scales for physical function, self-esteem, sexual life, public distress, and work were evaluated, and summarized in a total score. A higher value indicated a better quality of life. | Baseline to week 24 | 
| Selectivity Index at Week 24 | The selectivity index (SI) was used as a measure of orlistat's ability to target abdominal VAT loss compared to total adipose tissue lost. SI was calculated using the following equation: Mean % change in VAT divided by Mean % change in total fat mass. | Baseline to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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overweight, orlistat, body composition