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

April 22, 2026 updated by: University of California, San Francisco

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • Recruiting
        • UCSF Osher Center for Integrative Health
        • Principal Investigator:
          • Ashley E Mason, PhD
        • Contact:
        • Principal Investigator:
          • Leena S Pandya, ND
        • Sub-Investigator:
          • Rick M Hecht, MD
        • Sub-Investigator:
          • Wendy Hartogensis, PhD, MPH

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
Other Names:
  • Inert oral tablets
Drug: Colesevelam
Colesevelam in 625-mg tablets. Participants will take 3 tablets orally, twice daily (total daily dose 3.75 g) for 12 weeks.
Other Names:
  • Welchol
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.
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.
Other Names:
  • Inert oral tablets
Drug: Colesevelam
Colesevelam in 625-mg tablets. Participants will take 3 tablets orally, twice daily (total daily dose 3.75 g) for 12 weeks.
Other Names:
  • Welchol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retention
Time Frame: Enrollment to Week 27
Proportion completing all study blood draws after consent
Enrollment to Week 27
Adherence to study drug
Time Frame: Enrollment to Week 27
Proportion taking ≥80% of colesevelam doses
Enrollment to Week 27
Adherence to placebo
Time Frame: Enrollment to Week 27
Proportion taking ≥80% of placebo doses
Enrollment to Week 27
Acceptability
Time Frame: Week 27
Proportion endorsing "likely" or "very likely" to refer a co-worker to the study
Week 27
Likability
Time Frame: Week 27
Proportion endorsing "likely" or "very likely" to participate again
Week 27

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum PFAS Levels
Time Frame: 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.
Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urine Mold Mycotoxin Levels
Time Frame: Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27)
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
Time Frame: Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Investigators

  • Principal Investigator: 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
  • Study Director: Sarah Fisher, MS, University of California San Francisco, Osher Center for Integrative Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2026

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

November 6, 2025

First Submitted That Met QC Criteria

November 6, 2025

First Posted (Actual)

November 10, 2025

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ENGINE-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The investigative team will share de-identified data, an associated codebook, and an abbreviated study protocol.

IPD Sharing Time Frame

The investigative team will share data one year after all study participants' participation has concluded.

IPD Sharing Access Criteria

The investigative team will make data accessible via an online data sharing repository

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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