Assessing the Impact of a Bile Acid Sequestrant on Serum PFAS Levels in Highly Exposed Individuals
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Acceptability
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
All study staff will be masked. The only unmasked individuals will be the pharmacists dispensing in the medication/placebo.
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Colesevelam (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Colesevelam (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Acceptability
时间窗: Week 27
Proportion endorsing "likely" or "very likely" to refer a co-worker to the study
Likability
时间窗: Week 27
Proportion endorsing "likely" or "very likely" to participate again
Retention
时间窗: Enrollment to Week 27
Proportion completing all study blood draws after consent
Adherence to study drug
时间窗: Enrollment to Week 27
Proportion taking ≥80% of colesevelam doses
Adherence to placebo
时间窗: Enrollment to Week 27
Proportion taking ≥80% of placebo doses
次要结局
- Serum PFAS Levels(Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27))
- Serum PFAS Levels(Baseline (Week 0) to the end of each 12-week intervention period (Weeks 13 and 27))