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.

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

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.