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Recruiting NCT07226440

Examining a Novel Gastrointestinal Intervention to Negate Environmental Toxicants (ENGINE)

Phase I / Phase II Interventional Toxicant Exposure Firefighter Occupational Exposure to Chemicals

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Colesevelam, Placebo.
Who it may be relevant to
Registry conditions: Toxicant Exposure, Firefighter, Occupational Exposure to Chemicals. Basic parameters: from 18 years · Male.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Assessing the Impact of a Bile Acid Sequestrant on Serum PFAS Levels in Highly Exposed Individuals

Overview

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

  • Drug Colesevelam
    Colesevelam in 625-mg tablets. Participants will take 3 tablets orally, twice daily (total daily dose 3.75 g) for 12 weeks.
  • Drug Placebo
    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.

Primary outcome measures

  • Retention [Time frame: Enrollment to Week 27]
  • Adherence to study drug [Time frame: Enrollment to Week 27]
  • Adherence to placebo [Time frame: Enrollment to Week 27]
  • Acceptability [Time frame: Week 27]
  • Likability [Time frame: Week 27]
Secondary outcome measures (1)
  • Serum PFAS Levels [Time frame: Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Crossover
Masking
Triple blind
Primary purpose
Treatment

Study locations

United States · 1 center
  • UCSF Osher Center for Integrative Health — San Francisco

Publications

  • 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. PMID 6519377
  • 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. PMID 38074949
  • 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. PMID 33542478
  • 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. PMID 36573587
  • 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. PMID 38367552
  • 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. PMID 33819618
  • 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. PMID 37878255

Identifiers

NCT: NCT07226440 · ENGINE-01

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗