Colesevelam for Toxic Exposure

(ENGINE Trial)

Overseen By Leena Pandya, ND

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Francisco

Must not be taking: Bile acid sequestrants, Anabolic steroids

Disqualifiers: Diabetes, Gastroparesis, Hypertriglyceridemia, others

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether colesevelam, a medication, can reduce harmful chemicals in the blood of male firefighters exposed to high levels of PFAS, a group of man-made chemicals. Participants will begin with either colesevelam or a placebo (a pill with no active medicine) and switch after a set period. The study aims to determine if colesevelam can lower these chemical levels safely and effectively. Firefighters who work full-time in California, have been on duty for at least 10 years, and have high PFAS exposure might be suitable candidates. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications or treatments that may affect PFAS excretion, like activated charcoal or other bile acid sequestrants. If you're using substances that impact testosterone levels, like clomiphene or testosterone, you would also need to stop those.

Is there any evidence suggesting that colesevelam is likely to be safe for humans?

Research has shown that colesevelam is generally safe for people. This medication helps remove certain substances from the body. Studies indicate that colesevelam does not enter the bloodstream, making it unlikely to cause problems elsewhere in the body.

However, some individuals might experience muscle or bone discomfort. Real-world data show that while side effects can occur, they are usually related to digestion. Colesevelam is already FDA-approved for other uses, such as lowering cholesterol, which supports its safety.

In summary, while colesevelam has some known side effects, it is generally well-tolerated. Participants in this trial should be aware of these possible effects and discuss any concerns with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for toxic exposure?

Researchers are excited about colesevelam for toxic exposure because it offers a novel approach compared to current treatments. Unlike traditional therapies that may focus on neutralizing toxins directly or supporting the body's detox processes, colesevelam operates by binding bile acids in the gut. This mechanism could help reduce the overall toxin burden in the body by altering bile acid circulation. Moreover, colesevelam is already known for its safety profile in treating other conditions like high cholesterol, which could make it a promising option with fewer concerns about adverse effects.

What evidence suggests that colesevelam might be an effective treatment for toxic exposure?

This trial will compare the effects of colesevelam and a placebo on reducing PFAS levels. Studies have shown that colesevelam effectively reduces certain substances in the body. For instance, it significantly lowers LDL cholesterol, often called "bad cholesterol," and increases HDL cholesterol, known as "good cholesterol." Additionally, one study found that colesevelam reduced levels of teriflunomide, a chemical similar to some toxic substances, by over 96% in just 11 days. While this trial specifically focuses on reducing PFAS levels, existing research on colesevelam suggests it can help decrease unwanted chemicals in the blood. Overall, colesevelam has a strong track record of safely and effectively removing harmful substances from the body. ^{6 7 8 9 10}

Who Is on the Research Team?

Ashley E Mason, PhD

Principal Investigator

University of California San Francisco, Osher Center for Integrative Health

Leena Pandya, ND

Principal Investigator

University of California San Francisco, Osher Center for Integrative Health

Sarah Fisher, MS

Principal Investigator

University of California San Francisco, Osher Center for Integrative Health

Are You a Good Fit for This Trial?

This trial is for male firefighters aged 18-64 in California who have been on active duty for at least 10 years. They must be at high risk of PFAS exposure, willing to take a blood test, attend study visits in San Francisco Bay Area, and manage weekly surveys via text. Excluded are those with certain health conditions like diabetes or gastrointestinal disorders, or taking medications affecting PFAS excretion.

Inclusion Criteria

California resident

English-speaking

Access to a reliable internet connection

Exclusion Criteria

History of hypertriglyceridemia (triglycerides exceeding 500 mg/dL)

Type 1 or 2 diabetes

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive colesevelam or placebo for 12 weeks, followed by a 2-week washout period, and then crossover to the alternate treatment for another 12 weeks

26 weeks

Regular visits for monitoring and blood draws

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Colesevelam

Trial Overview The ENGINE trial is testing colesevelam against a placebo to see if it can lower blood levels of harmful substances (PFAS) and urine toxicants in firefighters exposed to chemicals. Participants will randomly receive either the drug or placebo and switch halfway through the six-month study.

How Is the Trial Designed?

Group I: Colesevelam first Active Control 2 Interventions

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.

Group II: Placebo first Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557815/

Colesevelam - StatPearls - NCBI Bookshelf Overall, colesevelam is a very safe drug to use with a long history of clinical use and study. The medication does not cause toxicity outside ...

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2009/022362s000ea.pdf

CENTER FOR DRUG EVALUATION AND RESEARCH The results indicate that colesevelam hydrochloride is not expected to be toxic to aquatic or terrestrial organisms at the highest projected ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0002870325003011

IMpact of therapY using coleSevelam treatment reducing ... Primary outcomes include safety/tolerability and change in total plasma BA levels. Secondary outcomes include changes in noninvasive hemodynamics, gut ...

4. hpr-rps.hres.ca hpr-rps.hres.ca/reg-content/summary-basis-decision-detailOne.php?linkID=SBD00031

Summary Basis of Decision - Health Canada Colesevelam hydrochloride administered alone or with a statin was shown to be effective in reducing LDL-C and total-C and in increasing HDL-C in patients with ...

5. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/full/10.1002/jcph.854

Effectiveness and Tolerability of Colesevelam HCl for ... After 11 days of treatment with colesevelam HCl, plasma concentrations of teriflunomide were, on average, reduced by > 96%. To achieve ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12262908/

Update of safety profile of bile acid sequestrants: A real- ... Colesevelam exhibited musculoskeletal toxicity, including ... colesevelam—based on real-world pharmacovigilance data. In addition ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/210895Orig1s000PharmR.pdf

Non-Clinical Review(s) - accessdata.fda.gov Welchol® is not absorbed, the risk of systemic toxicity is low. Safety concerns for colesevelam are well known and are primarily related to processes that.

8. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0328371

Update of safety profile of bile acid sequestrants: A real-world ... This large-scale FAERS study updates the safety profiles of BASs, highlighting distinct risk patterns and delayed complications.

9. federalregister.gov federalregister.gov/documents/2011/02/16/2011-3437/poison-prevention-packaging-requirements-proposed-exemption-of-powder-formulations-of-colesevelam

Poison Prevention Packaging Requirements The FDA provided CPSC staff with 151 distinct incidents of adverse events associated with colesevelam hydrochloride (Welchol®) reported through ...

10. file.medchemexpress.com file.medchemexpress.com/batch_PDF/HY-106539/Colesevelam-hydrochloride-SDS-MedChemExpress.pdf

Colesevelam hydrochloride-SDS- ... OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA. Reproductive ...