Clinical trial NCT06197763: Impact of Therapy Using Colesevelam Treatment Reducing Bile Acids in Patients With Fontan Circulation.
Official title: Impact of Therapy Using Colesevelam Treatment Reducing Bile Acids in Patients With Fontan Circulation (MYSTIC) Pilot Study.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Fontan Circulation
Lead sponsor: St. Boniface Hospital
Sponsor class: OTHER
First posted: 2024-01-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Drug safety
timeFrame: 20 Weeks
measure: Drug compliance
timeFrame: 20 weeks
measure: Impact of colesevelam on plasma & stool bile acid concentration.
timeFrame: 20 Weeks
Secondary outcomes:
measure: Impact of colesevelam on blood & urine metabolites.
timeFrame: 20 Weeks
measure: Impact of colesevelam on gut microbiome.
timeFrame: 20 Weeks
measure: Impact of colesevelam on hemodynamics.
timeFrame: 20 Weeks
measure: Gut microbiome comparison between healthy subjects and Fontan patients.
timeFrame: Baseline
Other outcomes:
Locations:
Study officials:
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