Maralixibat in Patients With Cystic Fibrosis and Constipation

Chronic constipation is common in children with cystic fibrosis (CF), likely due to impaired chloride channel function that reduces intestinal secretions. Standard osmotic laxatives often provide inadequate relief in this population. Maralixibat is an ileal bile acid transporter inhibitor (IBATi) that increases the amount of bile acids reaching the colon. Bile acids can enhance intestinal secretion, reduce transit time, and soften stool. This study will evaluate whether Maralixibat improves stool consistency in children with CF who experience constipation. We will enroll 20 children with CF and constipation, defined as a Bristol Stool Scale score \<4 for at least one week while on a stable laxative regimen. Each participant will receive Maralixibat for two weeks in addition to their usual laxatives. Families will record stool consistency and ease of defecation before and during treatment. The primary objective is to determine whether Maralixibat improves stool consistency to a Bristol Stool Scale score \>4. The secondary objective is to assess changes in ease of defecation using standardized questionnaires.

Constipation is a frequent gastrointestinal complication in children with cystic fibrosis (CF). Impaired CFTR-mediated chloride and water secretion leads to dehydrated intestinal contents, slowed transit, and difficulty with stool passage. Despite routine use of osmotic laxatives, many children with CF continue to experience hard stools, abdominal discomfort, and incomplete evacuation, highlighting the need for alternative therapeutic approaches. This study will evaluate the effect of Maralixibat on stool consistency and ease of defecation in children with CF who meet criteria for constipation while on a stable laxative regimen. The study uses a within-subjects design in which each participant serves as their own control. After a baseline observation period, participants will receive Maralixibat for two weeks in addition to their existing constipation management. Families will record stool characteristics and defecation symptoms using standardized tools provided by the study team. Changes in stool consistency and ease of defecation will be assessed by comparing pre-treatment and treatment-period data. The study is designed to generate preliminary evidence regarding the potential utility of IBAT inhibition as an adjunctive therapy for constipation in pediatric CF patients and to inform the feasibility and design of future controlled trials.

Inclusion Criteria * Ages 1 to 18 years. * Proven diagnosis of Cystic Fibrosis confirmed by genetic testing or sweat chloride testing. * Proven diagnosis of chronic constipation, defined as a Bristol Stool Scale (BSS) score \<3 while on a stable conventional constipation therapy regimen. * Stable conventional constipation medication regimen (no medication changes or dose adjustments) for at least 4 weeks prior to enrollment. Conventional therapy may include stool softeners, stimulant laxatives, or dietary interventions. Exclusion Criteria * Uncontrolled fat-soluble vitamin deficiency (Vitamin A, D, E, or K). * Changes to conventional constipation medication regimen within 4 weeks prior to initiation of Maralixibat. * Adequately treated chronic constipation, defined as a Bristol Stool Scale (BSS) score \>3 on the current regimen. * Known allergy or sensitivity to Maralixibat or any study-related ingredients. * Inability or unwillingness of the participant or legal guardian/representative to provide written informed consent.