Firefighter, Occupational Exposure to Chemicals, Toxicant Exposure
Conditions
Keywords
Per- and polyfluoroalkyl substances, PFAS, Firefighters, Occupational exposure, Bile acid sequestrants, Colesevelam
Brief summary
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.
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.
Interventions
DRUGColesevelam
Colesevelam in 625-mg tablets. Participants will take 3 tablets orally, twice daily (total daily dose 3.75 g) for 12 weeks.
DRUGPlacebo
Matching inert oral tablets designed to mimic colesevelam 625 mg tablets in size, shape, and color, but containing no active pharmaceutical ingredient. Participants will take 3 orally, twice per day for 12 weeks.
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
All study staff will be masked. The only unmasked individuals will be the pharmacists dispensing in the medication/placebo.
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.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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. * Unalterable plans to donate blood or plasma during the study participation period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention | Enrollment to Week 27 | Proportion completing all study blood draws after consent |
| Adherence to study drug | Enrollment to Week 27 | Proportion taking ≥80% of colesevelam doses |
| Adherence to placebo | Enrollment to Week 27 | Proportion taking ≥80% of placebo doses |
| Acceptability | Week 27 | Proportion endorsing "likely" or "very likely" to refer a co-worker to the study |
| Likability | Week 27 | Proportion endorsing "likely" or "very likely" to participate again |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum PFAS Levels | Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27) | Between-period and within-person changes in serum concentrations of the National Academy of Sciences, Engineering, and Medicine (NASEM)-7 PFAS score (sum of seven PFAS analytes). Higher scores mean higher PFAS levels in the body. Scores range from 0 to an unknown maximum. |
Countries
United States
Contacts
CONTACTAshley Mason, PhD
CONTACTLeena Pandya, ND
PRINCIPAL_INVESTIGATORAshley E Mason, PhD
University of California San Francisco, Osher Center for Integrative Health
PRINCIPAL_INVESTIGATORLeena Pandya, ND
University of California San Francisco, Osher Center for Integrative Health
STUDY_DIRECTORSarah Fisher, MS
University of California San Francisco, Osher Center for Integrative Health
Outcome results
None listed