Effect of Orlistat in Body Composition

• ClinicalTrials.gov Identifier: NCT00752726
• Recruitment Status: Completed
• First Posted: September 15, 2008
• Results First Posted: February 7, 2013
• Last Update Posted: March 8, 2013
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Obesity; Overweight	Drug: Orlistat; Drug: Placebo	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effects of Weight Reduction With Orlistat vs. Placebo on Changes in Body Composition
• Study Start Date: September 2008
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Orlistat; Orlistat 60 milligram (mg) capsules to be consumed orally with each meal 3 times per day	Drug: Orlistat; Weight loss treatment
Placebo Comparator: Placebo; Placebo to match Orlistat 60 mg capsules to be consumed orally with each meal 3 times per day.	Drug: Placebo; Inactive

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Week 24 in Abdominal VAT Mass [ Time Frame: Baseline to week 24 ]
   VAT was measured by the computed tomography (CT) scan.

Secondary Outcome Measures :

1. Change From Baseline to Week 12 in Abdominal VAT Mass [ Time Frame: Baseline to week 12 ]
   Abdominal VAT mass from baseline to week 12 was measured by CT scan.
2. Change From Baseline to Week 24 in Body Weight [ Time Frame: Baseline to week 24 ]
   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.
3. Change From Baseline to Week 24 in Total Fat Mass [ Time Frame: Baseline to week 24 ]
   Change in total fat mass was calculated from an average of three measurements at each visit from Echo Magnetic Resonance Imaging (EchoMRI).
4. Change From Baseline to Week 24 in Percentage Body Fat [ Time Frame: Baseline to week 24 ]
   Body fat was assessed through Bioelectrical Impedance Analysis (BIA).
5. Change From Baseline to Week 24 in Waist Circumference [ Time Frame: Baseline to week 24 ]
   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.
6. Change From Baseline to Week 24 in Percentage Liver Fat [ Time Frame: Baseline to week 24 ]
   For Liver fat, Intrahepatic lipids (IHL) were measured by Magnetic Resonance Spectroscopy (MRS).
7. Change From Baseline to Week 24 in Liver Fat [ Time Frame: Baseline to week 24 ]
   The liver fat was measured by CT scan in Hounsfield Units (HU).
8. Change From Baseline to Week 24 in Total Calories Expended for Physical Activity [ Time Frame: Baseline to week 24 ]
   Measurement of physical activity from Paffenbarger questionnaire. The number of caloried expended was representation of activity level: Higher calorie counts indicate higher activity
9. Change From Baseline to Week 24 in Quality of Life (QoL) Scores. [ Time Frame: Baseline to week 24 ]
   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.
10. Selectivity Index at Week 24 [ Time Frame: Baseline to 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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:

  1. Normal eating habits, consuming 3 meals a day (breakfast, lunch and dinner)
  2. Willing to follow a hypocaloric diet during the study to achieve weight loss
  3. 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.

Contacts and Locations

Locations

United States, Louisiana

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States, 70808

United States, North Carolina

Duke Clinical Research Unit

Durham, North Carolina, United States, 27710

Sweden

Sahlgrenska Academy

Goteborg, West Gothland, Sweden, 405 30

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Publications:

Smith SR, Stenlof KS, Greenway FL, McHutchison J, Schwartz SM, Dev VB, Berk ES, Kapikian R. Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial. Obesity (Silver Spring). 2011 Sep;19(9):1796-803. doi: 10.1038/oby.2011.143. Epub 2011 Jun 30.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00752726
• Other Study ID Numbers: W3600586
• First Posted: September 15, 2008
• Results First Posted: February 7, 2013
• Last Update Posted: March 8, 2013
• Last Verified: February 2013

Keywords provided by GlaxoSmithKline:

overweight, orlistat, body composition

Additional relevant MeSH terms:

Overweight; Body Weight; Orlistat; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Obesity Agents; Lipid Regulating Agents