Impact of Therapy Using Colesevelam Treatment Reducing Bile Acids in Patients With Fontan Circulation.

NCT06197763 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CTA/2023/001
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is the first pilot study proposing a novel therapeutic option treating patients with Fontan circulation (FC), a high-risk condition that has no definite treatment options available, other than heart or heart-liver transplantation. The investigator's identification of elevated BA and their association with adverse clinical - investigational features in Fontan patients are novel.

Conditions

Fontan Circulation

Outcome Measures

Primary Outcomes (3)

• Drug safety

  This outcome will be evaluated by identifying side effects experienced by any of the study participants throughout the study period. This information will be collected during biweekly phone calls to each of the study participants by the study coordinator. The study participants will also have the contact number of the study coordinator to notify them of any issues. The investigators have also established a "Data and drug safety monitoring board" which will review each of the side effects experienced by the study participants.

  20 Weeks

• Drug compliance

  This will be evaluated by checking with each study participant about their drug compliance and identifying the number of days, they have taken tablets as recommended.

  20 weeks

• Impact of colesevelam on plasma & stool bile acid concentration.

  Plasma \& stool bile acid concentration (total and their subcomponents) will be measured at baseline as well as after medication (placebo \& colesevelam) use.

  20 Weeks

Secondary Outcomes (4)

• Impact of colesevelam on blood & urine metabolites.

  20 Weeks

• Impact of colesevelam on gut microbiome.

  20 Weeks

• Impact of colesevelam on hemodynamics.

  20 Weeks

• Gut microbiome comparison between healthy subjects and Fontan patients.

  Baseline

Study Arms (2)

Fontan participants

EXPERIMENTAL

Participants will be randomized to be treated with either colesevelam (625 mg tablets - 3 tables twice per day) or placebo (3 tablets twice per day) for 6 weeks, interspersed by 8 week of washout time.

Drug: Colesevelam

Healthy control participants

SHAM COMPARATOR

These healthy control participants will be comparators to the randomized Fontan participants. Healthy controls will only undergo the baseline visit and will not receive the investigational drug or placebo.

Other: Control Arm

Interventions

Colesevelam DRUG

625 mg tablets - 3 tables twice per day of Colesevelam or placebo for 6 weeks (crossover), interspersed by 8 week of washout time.

Fontan participants

Control Arm OTHER

No Treatment: baseline assessment only

Healthy control participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• i) Of full age of consent (at least ≥ 18 years of age) at screening
• ii) Signed and dated written informed consent in accordance with ICF-GCP and local regulations prior to admission to the study
• iii) Male or female participants. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the participant informed consent form.
• iv) Diagnosis of Fontan circulation documented in the participant's medical record
• i) Of full age of consent (at least ≥ 18 years of age) at screening
• ii) Signed and dated written informed consent in accordance with ICF-GCP and local regulations prior to admission to the study
• iii) Male or female participants

You may not qualify if:

• i) Has previously received a heart or heart-liver transplant
• ii) Contraindication for using colesevelam, including allergy
• iii) Any physical or mental condition significantly affecting the participant's ability to participate in the investigator's opinion
• iv) Women who are pregnant, nursing, or who plan to become pregnant while in the trial
• i) Any known medical condition
• ii) Any physical or mental condition significantly affecting the participant's ability to participate in the investigator's opinion
• iii) Women who are pregnant or nursing at time of study visit

Sponsors & Collaborators

• St. Boniface Hospital: lead

Related Publications (1)

• Shah AH, Armstrong HK, Mittal I, Reimer A, Kunutsor SK, Ducas RA, Alizadeh K, Tam JW, Ravandi A, Dhingra S. IMpact of therapY using coleSevelam treatment reducing bile acids in patients with fonTan cIrCulation (MYSTIC): Rationale and study design. Am Heart J. 2026 Jan;291:81-88. doi: 10.1016/j.ahj.2025.08.011. Epub 2025 Aug 19.

  PMID: 40840821 DERIVED

MeSH Terms

Interventions

Colesevelam Hydrochloride

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Ashish Shah, M.D.

CONTACT

204-237-2023; ashah5@sbgh.mb.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, investigators, and everyone involved in study conduct or analysis or with any other interest in this double-blind study will remain blinded with regard to the randomization treatment assignments until after data collection completion. The access to the randomization code will be kept restricted until its release for analysis. The DSMB will be provided with unblinded data in order to allow them to review efficacy and safety and to fulfill their tasks as outlined in the DSMB charter.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Qualified Investigator

Model Details: prospective, double-blind, placebo cross-over, pilot study evaluating colesevelam (intestinal BA scavenger) therapy and placebo in 25 stable adult FC participants. These participants will be recruited from the cardiology clinics at the St. Boniface Hospital, specifically the Manitoba Adult Congenital Heart (MACH) Clinic. A further 25 age- and sex- matched healthy control participants will be recruited from advertising at St. Boniface Hospital and University of Manitoba. Healthy controls will only undergo the baseline visit and will not receive the investigational drug or placebo.

Study Record Dates

• First Submitted: October 4, 2023
• First Posted: January 9, 2024
• Study Start: June 1, 2024
• Primary Completion: November 1, 2025
• Study Completion: May 1, 2026
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share