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

NCT07226440 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ENGINE-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Firefighter; Toxicant Exposure; Occupational Exposure to Chemicals

Keywords

Per- and polyfluoroalkyl substances; PFAS; Firefighters; Occupational exposure; Bile acid sequestrants; Colesevelam

Outcome Measures

Primary Outcomes (5)

• 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

Secondary Outcomes (1)

• Serum PFAS Levels

  Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27)

Other Outcomes (2)

• Urine Mold Mycotoxin Levels

  Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27)

• Urine Environmental Toxicant Levels

  Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27)

Study Arms (2)

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.

Drug: Colesevelam; Drug: Placebo

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.

Drug: Colesevelam; Drug: Placebo

Interventions

Colesevelam DRUG

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

Also known as: Welchol

Colesevelam first; Placebo first

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.

Also known as: Inert oral tablets

Colesevelam first; Placebo first

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Osher Center for Integrative Health

San Francisco, California, 94115, United States

RECRUITING

Related Publications (7)

• 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 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.

  PMID: 38074949 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.

  PMID: 33542478 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.

  PMID: 36573587 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.

  PMID: 38367552 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.

  PMID: 33819618 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.

  PMID: 37878255 BACKGROUND

MeSH Terms

Conditions

Progressive Encephalomyelitis with Rigidity

Interventions

Colesevelam Hydrochloride

Intervention Hierarchy (Ancestors)

Allylamine; Amines; Organic Chemicals; Allyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Sarah Fisher, MS

  University of California San Francisco, Osher Center for Integrative Health

  STUDY DIRECTOR

Central Study Contacts

Ashley Mason, PhD

CONTACT

415-514-6820; enginestudy@ucsf.edu

Leena Pandya, ND

CONTACT

415-502-1619; leena.pandya@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study staff will be masked. The only unmasked individuals will be the pharmacists dispensing in the medication/placebo.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 6, 2025
• First Posted: November 10, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The investigative team will share data one year after all study participants' participation has concluded.
• Access Criteria: The investigative team will make data accessible via an online data sharing repository

Locations

US (1)