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

Phase 2Not Yet RecruitingNCT06197763

St. Boniface Hospital50 enrolled

Overview

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.

The investigators propose a 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. 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. Local research and ethics board approval will be obtained. Informed consent will be obtained from all participants. A further 25 age- and sex- matched healthy control participants will be recruited from advertising at St. Boniface Hospital and University of Manitoba. These healthy control participants will be comparators to the randomized Fontan participants at baseline. Recruitment of this group will be completed after all Fontan participants have been screened, consented, and randomized to ensure accuracy of age and sex matching. Age and sex matched participants will be +/- 3 years and not pregnant or nursing at time of study visit.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Fontan Circulation

Interventions

ColesevelamDRUG

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

Control ArmOTHER

No Treatment: baseline assessment only

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria - Fontan participants 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 Inclusion criteria - Healthy control participants 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 Exclusion criteria - Fontan participants 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 Exclusion criteria - Healthy control participants 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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 20 Weeks

Secondary Outcomes

Impact of colesevelam on blood & urine metabolites.

Plasma and urine metabolites will be measured before and after the drug (colesevelam) and placebo therapy.

Time frame: 20 Weeks

Impact of colesevelam on gut microbiome.

Stool samples before and after each medication (placebo and colesevelam) use will be analyzed to determine gut microbiome composition at baseline, and the impact of the colesevelam therapy on this composition.

Time frame: 20 Weeks

Impact of colesevelam on hemodynamics.

Each study participant will be evaluated by total body-impedance-based, non-invasive cardiac system (NICaS) derived hemodynamic parameters (cardiac output, cardiac index, stroke volume, stroke index, cardiac power output), before and after medication (placebo \& colesevelam) use.

Central Contacts

Ashish Shah, M.D.

CONTACT

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

Data from ClinicalTrials.gov

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