Maralixibat in Patients With Cystic Fibrosis and Constipation, A Within-Subjects Pilot Study

CHLA-23-00352

Chronic constipation is a feature of children with cystic fibrosis (CF). This is postulated to be a result of inhibition of secretory activity of the gastrointestinal luminal cells due to ineffective chloride channel function. Typical laxatives that work as osmotic agents fail to produce adequate relief in this population. Maralixibat is a non-systemic bile acid transport inhibitor (IBATi) that acts by interrupting bile acid reabsorption in the ileum thus interrupting the normal enterohepatic circulation. This interruption results in a larger volume of bile acids reaching the colon and being excreted in stool. Bile acids are known to decrease bowel transit time, increase mucosal permeability and secretions, as well as alter gut microbiota resulting in diarrhea. The overarching hypothesis of the study is that Maralixibat will improve stool consistency in children (Age \<18 years) with cystic fibrosis and constipation (Bristol Stool Scale \<4). Specifically, we aim to test the hypothesis that IBATi improves the consistency of stool to Bristol scale \>4 in children with CF and constipation. We will recruit a total of 20 patients with CF and constipation (defined as Bristol Stool Scale \<4 for 1 week prior to enrollment while on a stable laxative regimen for at least 4 weeks.) Design is a 'Within-Subjects' study by which each enrolled patient will take Maralixibat for 2 weeks total in addition to their stable laxative regimen during the study. Stool consistency \& ease of defecation will be recorded before and during the study period by families of enrolled patients via materials provided by the investigators. Stool consistency and ease of defecation will be compared before and after initiation of Maralixibat. The primary endpoint: Improvement in stool consistency to Bristol scale \>4 in children with CF and constipation. The secondary endpoint: Improvement in ease of defecation in children with CF and constipation. This will be measured via survey using a standardized scale (Bristol Stool Scale) and questionnaires developed by the research team. Analysis will involve comparison of pre-intervention to post-intervention stool consistency \& survey

2024-07-01

2026-06-30

2027-06-30

Not yet recruiting

Early phase I

20

Inclusion Criteria: * Age between 1-18 years Proven diagnosis of Cystic Fibrosis (via genetic testing or sweat chloride testing) Proven diagnosis of Chronic constipation (Bristol stool scale rating of \< 3 while on stable conventional therapy regimen) On stable (no medication changes or dose adjustments) conventional constipation medication regimen for chronic constipation (stool softeners, stimulant laxatives, dietary interventions) for at least 4 weeks. Exclusion Criteria: * The following are exclusion criteria for our study. All candidates meeting any of the exclusion criteria at baseline will be excluded from study participation: Uncontrolled fat-soluble vitamin deficiency (Vitamin A, E, D, or K) Changes to conventional constipation medication regimen \<4 weeks prior to initiation of Maralixibat Adequately treated chronic constipation on conventional regimen (Bristol stool scale rating of \> 3) Allergy or sensitivity to the study drugs or their ingredients Inability or unwillingness of individual or legal guardian/representative to given written informed consent.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2', 'PHASE3'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ESTIMATED'}}

2024-05-14