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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colesevelam first | Active Comparator | 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 first | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Colesevelam | Drug | Colesevelam in 625-mg tablets. Participants will take 3 tablets orally, twice daily (total daily dose 3.75 g) for 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Retention | Proportion completing all study blood draws after consent | Enrollment to Week 27 |
| Adherence to study drug | Proportion taking ≥80% of colesevelam doses | Enrollment to Week 27 |
| Adherence to placebo | Proportion taking ≥80% of placebo doses | Enrollment to Week 27 |
| Acceptability | Proportion endorsing "likely" or "very likely" to refer a co-worker to the study | Week 27 |
| Likability | Proportion endorsing "likely" or "very likely" to participate again | Week 27 |
| Measure | Description | Time Frame |
|---|---|---|
| Serum PFAS Levels | 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. | Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27) |
| Measure | Description | Time Frame |
|---|---|---|
| Urine Mold Mycotoxin Levels | Between-period and within-person changes in urine concentrations of mold mycotoxins | Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27) |
| Urine Environmental Toxicant Levels |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ashley Mason, PhD | Contact | 415-514-6820 | enginestudy@ucsf.edu | |
| Leena Pandya, ND | Contact | 415-502-1619 | leena.pandya@ucsf.edu |
| Name | Affiliation | Role |
|---|---|---|
| Ashley E Mason, PhD | University of California San Francisco, Osher Center for Integrative Health | Principal Investigator |
| Leena Pandya, ND | University of California San Francisco, Osher Center for Integrative Health |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Osher Center for Integrative Health | Recruiting | San Francisco | California | 94115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 6519377 | Background | Johnson JD, Gibson SJ, Ober RE. Cholestyramine-enhanced fecal elimination of carbon-14 in rats after administration of ammonium [14C]perfluorooctanoate or potassium [14C]perfluorooctanesulfonate. Fundam Appl Toxicol. 1984 Dec;4(6):972-6. doi: 10.1016/0272-0590(84)90235-5. | |
| 38074949 | Background | Mazumder NU, Hossain MT, Jahura FT, Girase A, Hall AS, Lu J, Ormond RB. Firefighters' exposure to per-and polyfluoroalkyl substances (PFAS) as an occupational hazard: A review. Front Mater. 2023;10:10.3389/fmats.2023.1143411. doi: 10.3389/fmats.2023.1143411. Epub 2023 Mar 23. |
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The investigative team will share de-identified data, an associated codebook, and an abbreviated study protocol.
The investigative team will share data one year after all study participants' participation has concluded.
The investigative team will make data accessible via an online data sharing repository
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| ID | Term |
|---|---|
| C566113 | Progressive Encephalomyelitis with Rigidity |
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| ID | Term |
|---|---|
| D000069472 | Colesevelam Hydrochloride |
| ID | Term |
|---|---|
| D000499 | Allylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D000498 | Allyl Compounds |
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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.
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All study staff will be masked. The only unmasked individuals will be the pharmacists dispensing in the medication/placebo.
|
| Placebo | Drug | 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. |
|
|
Between-period and within-person changes in urine concentrations of environmental toxicants
| Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27) |
| Sarah Fisher, MS | University of California San Francisco, Osher Center for Integrative Health | Study Director |
| 33542478 | Background | Young AS, Sparer-Fine EH, Pickard HM, Sunderland EM, Peaslee GF, Allen JG. Per- and polyfluoroalkyl substances (PFAS) and total fluorine in fire station dust. J Expo Sci Environ Epidemiol. 2021 Sep;31(5):930-942. doi: 10.1038/s41370-021-00288-7. Epub 2021 Feb 5. |
| 36573587 | Background | Lucas K, Gaines LGT, Paris-Davila T, Nylander-French LA. Occupational exposure and serum levels of per- and polyfluoroalkyl substances (PFAS): A review. Am J Ind Med. 2023 May;66(5):379-392. doi: 10.1002/ajim.23454. Epub 2022 Dec 27. |
| 38367552 | Background | Moller JJ, Lyngberg AC, Hammer PEC, Flachs EM, Mortensen OS, Jensen TK, Jurgens G, Andersson A, Soja AMB, Lindhardt M. Substantial decrease of PFAS with anion exchange resin treatment - A clinical cross-over trial. Environ Int. 2024 Mar;185:108497. doi: 10.1016/j.envint.2024.108497. Epub 2024 Feb 13. |
| 33819618 | Background | Ducatman A, Luster M, Fletcher T. Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting. Environ Toxicol Pharmacol. 2021 Jul;85:103650. doi: 10.1016/j.etap.2021.103650. Epub 2021 Apr 2. |
| 37878255 | Background | Seyyedsalehi MS, Boffetta P. Per- and Poly-fluoroalkyl Substances (PFAS) Exposure and Risk of Kidney, Liver, and Testicular Cancers: A Systematic Review and Meta-Analysis. Med Lav. 2023 Oct 24;114(5):e2023040. doi: 10.23749/mdl.v114i5.15065. |
| D000475 |
| Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |