Weight Loss Aid in an Exposed Population

Study Overview
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Brief Summary
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This study will explore whether the use of orlistat results in weight loss that is accompanied by a reduction in the body burdens of polybrominated biphenyls (PBB) and other Persistent Organic Pollutants (POPs).

Detailed Description
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Millions of people living in Michigan were exposed to brominated flame retardants (polybrominated biphenyls or PBB) as a result of the largest agricultural disaster in US history. Over the past six years, Emory researchers have tested nearly 900 Michigan residents and determined that 60% still had PBB in their bodies from that disaster. PBB is stored in body fat and the researchers at Emory have been asked by community members if weight loss might reduce their body burdens of PBB and other lipophilic chemicals. In an effort to understand how PBB and other persistent organic pollutants (POPs) are eliminated, the researchers are conducting a randomized trial of orlistat versus placebo. Orlistat is an over-the-counter product approved by the FDA for weight loss and works by increasing excretion of fat into the stool. Since PBB is stored in body fat, the researchers hypothesize that orlistat may reduce the body burden of PBB and other POPs. This study is a randomized, placebo-controlled trial of orlistat (at the dose available over-the-counter) plus diet and exercise for 6 months in a population with elevated PBB levels. Participants will be healthy overweight adults and orlistat will be taken as directed for the approved indication (weight loss).

Official Title
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Use of a Weight Loss Aid in a Population Exposed to Polybrominated Biphenyls (PBB)

Conditions
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Polybrominated Biphenyl Poisoning

Intervention / Treatment
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* Drug: Orlistat
* Drug: Placebo capsule
* Dietary Supplement: Multivitamin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: current or recent (within the last five years) serum PBB level of ≥1ppb, or are a member of a sub-group likely to have high serum PBB (former chemical worker, family member of former chemical worker, lived on a farm with animals that were quarantined because of PBB exposure) at least 18 years old currently reside in Michigan able to participate in examinations and laboratory tests (a lipid panel, liver function test, thyroid function and and creatinine levels) done at at a local health department or other medical health facility and to be able to engage in moderate physical activity (e.g. walking) participants with undiagnosed abdominal pain or diarrhea, Crohn's disease, Ulcerative Colitis, Celiac Disease, treated diabetes or treated thyroid disorder, will only be eligible following consultation with their primary care provider any participant using levothyroxine will be instructed to take their dosage 4 hours before or after Orlistat in order to maintain eligibility Exclusion Criteria: BMI<25 abnormal liver function abnormal creatinine levels abnormal thyroid levels (TSH) have type 1 diabetes have had an organ transplant are pregnant or lactating current use of weight-loss medications, oral steroids, Coumadin, warfarin or Cyclosporine have a diagnosed problem absorbing food, or have an eating disorder a history of bariatric surgery, pancreatitis, kidney stones, gall bladder disorder or a serious chronic disease (e.g. uncontrolled diabetes, congestive heart failure, chronic kidney disease) allergies to any ingredients of the Orlistat over-the-counter (OTC) capsules participants will become ineligible at any point during the study if they begin a medical regimen involving any of the above medications

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orlistat Weight Loss Aid<br>Participants randomized to take orlistat at the over-the-counter dose for six months. Diet and exercise plus a daily multivitamin will also be recommended and monitored. | Drug: Orlistat<br>* Participants will be instructed to take one 60mg capsule of orlistat with each meal containing fat, up to three capsules daily, for six months.<br>* Other names: Alli;Dietary Supplement: Multivitamin<br>* A multivitamin will be provided to be taken once daily, at bedtime.<br>|
| Placebo Comparator: Placebo<br>Participants randomized to take a placebo to match orlistat at the over-the-counter dose for six months. Diet and exercise plus a daily multivitamin will also be recommended and monitored. | Drug: Placebo capsule<br>* Participants will be instructed to take one placebo capsule to match 60mg of orlistat with each meal containing fat, up to three capsules daily, for six months.<br>Dietary Supplement: Multivitamin<br>* A multivitamin will be provided to be taken once daily, at bedtime.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Participants will have their weight measured in light clothing without shoes on a regularly calibrated digital scale. | Screening, 3 and 6 months follow up visits | 
| Change in Body Mass Index | Body Mass Index is a weight-to-height ratio, calculated by dividing one's weight in kilograms by the square of one's height in meters and used as an indicator of obesity and underweight. Participants will have their weight measured in light clothing without shoes on a regularly calibrated digital scale. Height will be measured using a well-mounted stadiometer. | Screening, 3 and 6 months follow up visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in dietary intake using Automated Self-administered 24-hour Recall score | Participants will be asked to recall their food and beverage intake during the previous 24-hour period using the most recent version of the Automated Self-Administered 24-hour (ASA24) Recall - an interactive web-based system sponsored by NCI - that prompts participants for food description details and automatically codes and calculates nutrient intakes. Details are described here: https://epi.grants.cancer.gov/hei/developing.html Using data collected from ASA24 recalls, two outcomes will be assessed: diet quality and percent of calories from fat. Diet quality will be assessed with the Healthy Eating Index (HEI-2015). This Index contains 13 components that sum to a maximum of 100 points (minimum 0 points; higher scores are better). Percent of calories from fat will be calculated by dividing the total calories from fat by the total calories consumed.These are continuous variables. We will determine if the percent calories from fat is reduced during the course of the trial. | Screening, 3 and 6 months follow up visits | 
| Change in physical activity | Change in physical activity will be assessed using the Women's Health Initiative Physical Activity Questionnaire (WHI-PAQ) which assesses physical activity across several domains (leisure, domestic and yard, work and transportation-related activities) and when scored can provide metrics of total minutes/week spent in various categories of activity and can be transformed to metabolic equivalent (MET) values for overall activity. A physical activity summary variable will be created by combining frequency, duration and MET-estimated intensity: (Frequency of activity per week × Minutes per session × MET for that activity) / (60 min/hour) | Screening, 3 and 6 months follow up visits | 
| Change in serum concentration of polybrominated biphenyl (PBB) 153 | PBB is an organic bromine compound that is environmentally toxic and is classified as a persistent organic pollutant. PBB 153 concentration in serum is measured in parts per billion (ppb). | Screening, 3 and 6 months follow up visits | 
| Change in serum concentration of polybrominated diphenyl ether (PBDE) 47 | PBDE is an organic bromine compound that is environmentally toxic and is classified as a persistent organic pollutant. PBDE 47 concentration in serum is measured in ppb. | Screening, 3 and 6 months follow up visits | 
| Change in serum concentration of polychlorinated biphenyl (PCB) 118 | PCB is an organic chlorine compound that is environmentally toxic and is classified as a persistent organic pollutant. PCB 118 concentration in serum is measured in ppb. | Screening, 3 and 6 months follow up visits | 
| Change in serum concentration of PCB 138 | PCB is an organic chlorine compound that is environmentally toxic and is classified as a persistent organic pollutant. PCB 138 concentration in serum is measured in ppb. | Screening, 3 and 6 months follow up visits | 
| Change in serum concentration of PCB 153 | PCB is an organic chlorine compound that is environmentally toxic and is classified as a persistent organic pollutant. PCB 153 concentration in serum is measured in ppb. | Screening, 3 and 6 months follow up visits | 
| Change in serum concentration of PCB 180 | PCB is an organic chlorine compound that is environmentally toxic and is classified as a persistent organic pollutant. PCB 180 concentration in serum is measured in ppb. | Screening, 3 and 6 months follow up visits | 
| Change in serum concentration of dichlorodiphenyltrichloroethane (DDT) | DDT is a pesticide that was banned in 1972. High levels of DDT can impact the nervous system, including causing tremors or seizures. DDT concentration in serum is measured in ppb. | Screening, 3 and 6 months follow up visits | 
| Change in serum concentration of dichlorodiphenyldichloroethylene (DDE) | DDE is a chemical produced by the breakdown of DDT. High levels of DDE can impact lactation and increase the risk of preterm birth. DDE concentration in serum is measured in ppb. | Screening, 3 and 6 months follow up visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polybrominated Biphenyl Exposure, Gastrointestinal lipase inhibitor