Polybrominated Biphenyl Poisoning
Conditions
Keywords
Polybrominated Biphenyl Exposure, Gastrointestinal lipase inhibitor
Brief summary
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
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).
Interventions
DRUGOrlistat
Participants will be instructed to take one 60mg capsule of orlistat with each meal containing fat, up to three capsules daily, for six months.
DRUGPlacebo 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.
DIETARY_SUPPLEMENTMultivitamin
A multivitamin will be provided to be taken once daily, at bedtime.
Sponsors
Healthway Compounding Pharmacy
Michigan Public Health Departments
National Institute of Environmental Health Sciences (NIEHS)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight | Enrollment, Month 3, Month 6 | Participant weight, in kilograms, was measured in light clothing without shoes on a regularly calibrated digital scale. |
| Body Mass Index (BMI) | Enrollment, Month 3, Month 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentration of Polybrominated Diphenyl Ether (PBDE) 47 | Enrollment, Month 3, Month 6 | 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. |
| Serum Concentration of Polychlorinated Biphenyl (PCB) 118 | Enrollment, Month 3, Month 6 | 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. |
| Serum Concentration of PCB 138 | Enrollment, Month 3, Month 6 | 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 |
| Serum Concentration of PCB 180 | Enrollment, Month 3, Month 6 | 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 |
| Serum Concentration of Dichlorodiphenyldichloroethylene (DDE) | Enrollment, Month 3, Month 6 | 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. |
| Serum Concentration of PCB 153 | Enrollment, Month 3, Month 6 | 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. |
| Serum Concentration of Polybrominated Biphenyl (PBB) 153 | Enrollment, Month 3, Month 6 | 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). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Michigan polybrominated biphenyls (PBB) Research Registry. Participant enrollment began September 14, 2018 and all follow-up assessments were completed by June 30, 2022.
Pre-assignment details
100 individuals gave consent to participate in the study and were randomized to a study arm. One participant who was randomized to the Orlistat arm did not begin taking the study medication and did not complete the first study visit.
Participants by arm
| Arm | Count |
|---|---|
| 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 were also recommended and monitored. | 46 |
| 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 were also recommended and monitored. | 45 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | Orlistat Weight Loss Aid |
|---|---|---|---|
| Age, Continuous | 59.4 years STANDARD_DEVIATION 9.9 | 59.4 years STANDARD_DEVIATION 9.6 | 59.5 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 89 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 43 Participants | 86 Participants | 43 Participants |
| Region of Enrollment United States | 46 Participants | 91 Participants | 45 Participants |
| Sex: Female, Male Female | 28 Participants | 55 Participants | 27 Participants |
| Sex: Female, Male Male | 18 Participants | 36 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 51 |
| other Total, other adverse events | 28 / 49 | 41 / 51 |
| serious Total, serious adverse events | 3 / 49 | 0 / 51 |
Outcome results
Primary
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.
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-five participants were not able to attend the Month 3 study visit in person; 23 due to the COVID-19 pandemic and an additional 2 due to other reasons. All of participants who were unable to have the in-person Month 3 visit provided a self-measured weight. Mean BMI calculated using weight measured per protocol and self-measured are reported separately.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Body Mass Index (BMI) | Enrollment | 32.3 kg/m^2 | Standard Deviation 5.4 |
| Placebo | Body Mass Index (BMI) | Month 3 - BMI calculated with weight measured by study staff | 31.5 kg/m^2 | Standard Deviation 5.9 |
| Placebo | Body Mass Index (BMI) | Month 3 - BMI calculated with weight self-measured by participant | 31.6 kg/m^2 | Standard Deviation 5.6 |
| Placebo | Body Mass Index (BMI) | Month 6 | 31.4 kg/m^2 | Standard Deviation 5.8 |
| Orlistat Weight Loss Aid | Body Mass Index (BMI) | Month 6 | 30.2 kg/m^2 | Standard Deviation 5 |
| Orlistat Weight Loss Aid | Body Mass Index (BMI) | Enrollment | 31.7 kg/m^2 | Standard Deviation 5 |
| Orlistat Weight Loss Aid | Body Mass Index (BMI) | Month 3 - BMI calculated with weight self-measured by participant | 32.3 kg/m^2 | Standard Deviation 6.4 |
| Orlistat Weight Loss Aid | Body Mass Index (BMI) | Month 3 - BMI calculated with weight measured by study staff | 29.9 kg/m^2 | Standard Deviation 4.1 |
Primary
Weight
Participant weight, in kilograms, was measured in light clothing without shoes on a regularly calibrated digital scale.
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-five participants were not able to attend the Month 3 study visit in person; 23 due to the Coronavirus 2019 (COVID-19) pandemic and an additional 2 due to other reasons. All of participants who were unable to have the in-person Month 3 visit provided a self-measured weight. Mean weights measured per protocol and self-measured are reported separately.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Weight | Enrollment | 91.3 kilograms (kg) | Standard Deviation 16.4 |
| Placebo | Weight | Month 3 measured per protocol by study staff | 88.6 kilograms (kg) | Standard Deviation 18.1 |
| Placebo | Weight | Month 3 self-measured by participant | 90.4 kilograms (kg) | Standard Deviation 14.1 |
| Placebo | Weight | Month 6 | 89.2 kilograms (kg) | Standard Deviation 17.1 |
| Orlistat Weight Loss Aid | Weight | Month 6 | 88.1 kilograms (kg) | Standard Deviation 17.7 |
| Orlistat Weight Loss Aid | Weight | Enrollment | 92.3 kilograms (kg) | Standard Deviation 17.8 |
| Orlistat Weight Loss Aid | Weight | Month 3 self-measured by participant | 93.2 kilograms (kg) | Standard Deviation 20.2 |
| Orlistat Weight Loss Aid | Weight | Month 3 measured per protocol by study staff | 87.4 kilograms (kg) | Standard Deviation 15.9 |
Secondary
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.
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-three participants were not able to attend the Month 3 study visit in person due to the COVID-19 pandemic and did not have blood drawn at this time point. An additional 2 participants did not attend the Month 3 visit in person and one had blood collected and shipped to the study lab by their physician.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Serum Concentration of Dichlorodiphenyldichloroethylene (DDE) | Month 6 | 0.573 ng/mL |
| Placebo | Serum Concentration of Dichlorodiphenyldichloroethylene (DDE) | Enrollment | 0.535 ng/mL |
| Placebo | Serum Concentration of Dichlorodiphenyldichloroethylene (DDE) | Month 3 | 0.539 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Dichlorodiphenyldichloroethylene (DDE) | Month 6 | 0.498 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Dichlorodiphenyldichloroethylene (DDE) | Enrollment | 0.490 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Dichlorodiphenyldichloroethylene (DDE) | Month 3 | 0.490 ng/mL |
Secondary
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
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-three participants were not able to attend the Month 3 study visit in person due to the COVID-19 pandemic and did not have blood drawn at this time point. An additional 2 participants did not attend the Month 3 visit in person and one had blood collected and shipped to the study lab by their physician.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Serum Concentration of PCB 138 | Enrollment | 0.081 ng/mL |
| Placebo | Serum Concentration of PCB 138 | Month 3 | 0.070 ng/mL |
| Placebo | Serum Concentration of PCB 138 | Month 6 | 0.078 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 138 | Enrollment | 0.064 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 138 | Month 3 | 0.066 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 138 | Month 6 | 0.064 ng/mL |
Secondary
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.
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-three participants were not able to attend the Month 3 study visit in person due to the COVID-19 pandemic and did not have blood drawn at this time point. An additional 2 participants did not attend the Month 3 visit in person and one had blood collected and shipped to the study lab by their physician.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Serum Concentration of PCB 153 | Enrollment | 0.122 ng/mL |
| Placebo | Serum Concentration of PCB 153 | Month 3 | 0.100 ng/mL |
| Placebo | Serum Concentration of PCB 153 | Month 6 | 0.114 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 153 | Enrollment | 0.096 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 153 | Month 3 | 0.105 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 153 | Month 6 | 0.105 ng/mL |
Secondary
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
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-three participants were not able to attend the Month 3 study visit in person due to the COVID-19 pandemic and did not have blood drawn at this time point. An additional 2 participants did not attend the Month 3 visit in person and one had blood collected and shipped to the study lab by their physician.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Serum Concentration of PCB 180 | Enrollment | 0.116 ng/mL |
| Placebo | Serum Concentration of PCB 180 | Month 3 | 0.101 ng/mL |
| Placebo | Serum Concentration of PCB 180 | Month 6 | 0.112 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 180 | Enrollment | 0.108 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 180 | Month 3 | 0.114 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of PCB 180 | Month 6 | 0.121 ng/mL |
Secondary
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).
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-three participants were not able to attend the Month 3 study visit in person due to the COVID-19 pandemic and did not have blood drawn at this time point. An additional 2 participants did not attend the Month 3 visit in person and one had blood collected and shipped to the study lab by their physician.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Serum Concentration of Polybrominated Biphenyl (PBB) 153 | Enrollment | 0.454 ng/mL |
| Placebo | Serum Concentration of Polybrominated Biphenyl (PBB) 153 | Month 3 | 0.355 ng/mL |
| Placebo | Serum Concentration of Polybrominated Biphenyl (PBB) 153 | Month 6 | 0.481 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polybrominated Biphenyl (PBB) 153 | Enrollment | 0.276 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polybrominated Biphenyl (PBB) 153 | Month 3 | 0.395 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polybrominated Biphenyl (PBB) 153 | Month 6 | 0.290 ng/mL |
Secondary
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.
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-three participants were not able to attend the Month 3 study visit in person due to the COVID-19 pandemic and did not have blood drawn at this time point. An additional 2 participants did not attend the Month 3 visit in person and one had blood collected and shipped to the study lab by their physician.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Serum Concentration of Polybrominated Diphenyl Ether (PBDE) 47 | Enrollment | 0.032 ng/mL |
| Placebo | Serum Concentration of Polybrominated Diphenyl Ether (PBDE) 47 | Month 3 | 0.034 ng/mL |
| Placebo | Serum Concentration of Polybrominated Diphenyl Ether (PBDE) 47 | Month 6 | 0.029 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polybrominated Diphenyl Ether (PBDE) 47 | Enrollment | 0.028 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polybrominated Diphenyl Ether (PBDE) 47 | Month 3 | 0.025 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polybrominated Diphenyl Ether (PBDE) 47 | Month 6 | 0.025 ng/mL |
Secondary
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.
Time frame: Enrollment, Month 3, Month 6
Population: This analysis includes participants who attended both the Enrollment and Month 3 visits, and also those who completed the Month 6 visit. Twenty-three participants were not able to attend the Month 3 study visit in person due to the COVID-19 pandemic and did not have blood drawn at this time point. An additional 2 participants did not attend the Month 3 visit in person and one had blood collected and shipped to the study lab by their physician.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Serum Concentration of Polychlorinated Biphenyl (PCB) 118 | Enrollment | 0.035 ng/mL |
| Placebo | Serum Concentration of Polychlorinated Biphenyl (PCB) 118 | Month 3 | 0.031 ng/mL |
| Placebo | Serum Concentration of Polychlorinated Biphenyl (PCB) 118 | Month 6 | 0.028 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polychlorinated Biphenyl (PCB) 118 | Enrollment | 0.026 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polychlorinated Biphenyl (PCB) 118 | Month 3 | 0.024 ng/mL |
| Orlistat Weight Loss Aid | Serum Concentration of Polychlorinated Biphenyl (PCB) 118 | Month 6 | 0.025 ng/mL |