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

University of California San Francisco (UCSF)

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Toxicant Exposure; Occupational Exposure to Chemicals; Firefighter

Treatments: Drug: Colesevelam; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07226440

ENGINE-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: Male

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male firefighter
• California resident
• Age 18-64
• Full-time, active-duty (fire suppression and/or arson investigation)
• 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)

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.
• More than one blood or plasma donation in the past 12 months and/or unalterable plans to donate blood or plasma during the study participation period
• Use of clomiphene, testosterone, human chorionic gonadotropin, anabolic steroids, anastrozole or any other substances that may impact testosterone levels in males

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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40 participants in 2 patient groups, including a placebo group

Colesevelam first

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Colesevelam

Placebo first

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Colesevelam