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

Impact of Therapy Using Colesevelam Treatment Reducing Bile Acids in Patients With Fontan Circulation (MYSTIC) Pilot Study.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Fontan Circulation
• Intervention / Treatment: Drug: Colesevelam; Other: Control Arm

Detailed Description

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
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ashish Shah, M.D.; Phone Number: 204-237-2023; Email: ashah5@sbgh.mb.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fontan participants; 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; 625 mg tablets - 3 tables twice per day of Colesevelam or placebo for 6 weeks (crossover), interspersed by 8 week of washout time.
Sham Comparator: Healthy control participants; 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; No Treatment: baseline assessment only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of colesevelam on blood & urine metabolites.	Plasma and urine metabolites will be measured before and after the drug (colesevelam) and placebo therapy.	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.	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.	20 Weeks
Gut microbiome comparison between healthy subjects and Fontan patients.	The gut microbiome will be compared between healthy subjects and patients with Fontan circulation at baseline.	Baseline

Collaborators and Investigators

• Sponsor: St. Boniface Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: October 4, 2023
• First Submitted That Met QC Criteria: December 26, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride
• Other Study ID Numbers: CTA/2023/001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes