Examining a Novel Gastrointestinal Intervention to Negate Environmental Toxicants (ENGINE)
Purpose
This randomized, placebo-controlled crossover trial will test the feasibility and acceptability of using colesevelam in male firefighters with high per- and polyfluoroalkyl substances (PFAS) exposure. This trial will also explore whether colesevelam lowers blood PFAS levels and urine environmental toxicant and mold mycotoxin levels.
Conditions
- Toxicant Exposure
- Firefighter
- Occupational Exposure to Chemicals
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male firefighter, active or retired - California resident - Age 18 or older - English-speaking - Access to a reliable internet connection - Willing to attend 3 in-person study visits in the San Francisco Bay Area over about 6.5 months - Willing to receive weekly text message reminders to complete online surveys - Willing to complete a mail-based, at-home finger-prick blood test - Willing to take 3 tablets (each tablet about the size of a multivitamin) orally twice daily for a total of 6 months - Evaluated by study team to have an elevated risk of PFAS exposure (e.g., duration of firefighting service, prior NASEM-7 result greater than or equal to 10 ng/mL)
Exclusion Criteria
- Gastroparesis or other severe gastrointestinal motility disorders - Bowel obstruction - History of major gastrointestinal tract surgery - Dysphagia or difficulty swallowing (due to tablet size) - History of hypertriglyceridemia (triglycerides exceeding 500 mg/dL) - History of hypertriglyceridemia-induced pancreatitis - Type 1 or 2 diabetes - History of fat-soluble vitamin deficiencies, i.e., vitamins A, D, E, or K - Phenylketonuria - History of known bleeding/clotting disorders - Medications or treatments that may impact the excretion of PFAS, such as activated charcoal, other bile acid sequestrants, chelation therapies, etc. - More than one blood or plasma donation in the past 12 months and/or unalterable plans to donate blood or plasma during the study participation period - Use of clomiphene, testosterone, human chorionic gonadotropin, anabolic steroids, anastrozole or any other substances that may impact testosterone levels in males
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Intervention Model Description
- This is a randomized, double-blind, placebo-controlled, crossover trial with a 2-week washout between treatment periods. Participants are assigned to one of two sequences: colesevelam followed by placebo, or placebo followed by colesevelam.
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
- Masking Description
- All study staff will be masked. The only unmasked individuals will be the pharmacists dispensing in the medication/placebo.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Colesevelam first |
Participants randomized to this arm will receive colesevelam, taking 3 tablets twice daily for 12 weeks, followed by a 2-week washout period, and then 12 weeks of matching placebo tablets taken on the same schedule. Both the study drug and the placebo will be provided in identical-appearing bottles to maintain blinding. |
|
|
Placebo Comparator Placebo first |
Participants randomized to this arm will receive placebo tablets, taking 3 tablets twice daily for 12 weeks, followed by a 2-week washout period, and then 12 weeks of colesevelam (3 tablets twice daily). Both the study drug and the placebo will be provided in identical-appearing bottles to maintain blinding. |
|
Recruiting Locations
San Francisco, California 94115
More Details
- Status
- Recruiting
- Sponsor
- University of California, San Francisco
Detailed Description
Firefighters experience elevated exposure to per- and polyfluoroalkyl substances (PFAS) through firefighting foams, turnout gear, and dust in fire stations. PFAS persist in the body due to their long biological half-lives, leading to bioaccumulation and raising concern for adverse effects on hormone regulation, immune function, reproduction, and cancer risk. Despite growing awareness, there are no approved treatment options to reduce PFAS levels in humans. Bile acid sequestrants, such as colesevelam, bind bile acids in the gastrointestinal tract and may interrupt enterohepatic recirculation of PFAS, thereby enhancing elimination. Observational studies and one small randomized trial suggest that bile acid sequestrants can meaningfully reduce PFAS levels. This trial will evaluate the feasibility, adherence, and acceptability of colesevelam in male firefighters with elevated PFAS, while exploring its effects on serum PFAS concentrations and urine environmental toxicant and mold mycotoxin levels.