Weight Loss Aid in an Exposed Population

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

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).

Study Overview

• Status: Completed
• Conditions: Polybrominated Biphenyl Poisoning
• Intervention / Treatment: Drug: Orlistat; Dietary supplement: Multivitamin; Drug: Placebo capsule

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Michele Marcus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orlistat Weight Loss Aid; 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; Participants will be instructed to take one 60mg capsule of orlistat with each meal containing fat, up to three capsules daily, for six months.; Other Names: Alli; Dietary supplement: Multivitamin; A multivitamin will be provided to be taken once daily, at bedtime.
Placebo Comparator: Placebo; 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.	Dietary supplement: Multivitamin; A multivitamin will be provided to be taken once daily, at bedtime.; Drug: Placebo capsule; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Participant weight, in kilograms, was measured in light clothing without shoes on a regularly calibrated digital scale.	Enrollment, Month 3, Month 6
Body Mass Index (BMI)	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 had their weight measured in light clothing without shoes on a regularly calibrated digital scale. Height is measured using a well-mounted stadiometer.	Enrollment, Month 3, Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 nanograms per milliliter (ng/mL).	Enrollment, Month 3, Month 6
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 ng/mL.	Enrollment, Month 3, Month 6
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 ng/mL.	Enrollment, Month 3, Month 6
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 ng/mL	Enrollment, Month 3, Month 6
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 ng/mL.	Enrollment, Month 3, Month 6
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 ng/mL	Enrollment, Month 3, Month 6
Serum Concentration of Dichlorodiphenyldichloroethylene (DDE)	DDE is a chemical produced by the breakdown of dichlorodiphenyltrichloroethane (DDT). High levels of DDE can impact lactation and increase the risk of preterm birth. DDE concentration in serum is measured in ng/mL.	Enrollment, Month 3, Month 6

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Environmental Health Sciences (NIEHS); Healthway Compounding Pharmacy in central Michigan; Michigan Public Health Departments
• Investigators: Principal Investigator: Michele Marcus, PhD, MPH, School of Public Health, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2018
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: June 28, 2018
• First Posted (Actual): July 11, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Polybrominated Biphenyl Exposure; Gastrointestinal lipase inhibitor
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Body Weight; Body Weight Changes; Poisoning; Weight Loss; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipid Regulating Agents; Anti-Obesity Agents; Orlistat
• Other Study ID Numbers: IRB00099231; R01ES025775 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No