Choline chloride injections for adolescents and adults with intestinal failure on long-term parenteral support

A Phase 2b/3 Randomized Open-Label Dose-Selection Study With Open-Label Extension and Randomized Double-Blind, Placebo-Controlled Study With Open-Label Extension to Evaluate the Safety and Efficacy of Choline Chloride for Injection (Low Dose and High Dose) Versus Placebo in Adolescents and Adults With Intestinal Failure Receiving Long-Term Parenteral Support

This will test whether low or high doses of choline chloride injections help adolescents and adults with intestinal failure who rely on long-term parenteral support.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 129 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: Protara Therapeutics (Industry-sponsored)
• Locations: 14 sites (Aurora, Colorado and 13 other locations)
• Trial ID: NCT06910943 on ClinicalTrials.gov

What this trial studies

This is a Phase 2b/3 program that begins with an open-label dose-selection phase to evaluate safety, tolerability, and how the drug is distributed, followed by a randomized double-blind, placebo-controlled phase to test efficacy, each with an open-label extension of about a year. Adolescents (12 to <18) and adults (≥18) who have been on stable long-term parenteral support are eligible, and the dose-selection phase will pick two of three doses for the blinded comparison. Key outcomes include safety, liver-related measures, and correction of choline deficiency in patients receiving parenteral nutrition. The design combines initial open-label exposure to choose optimal doses with a subsequent placebo-controlled comparison to provide more rigorous efficacy data.

Who should consider this trial

Good fit: Adolescents (12 to <18) and adults (≥18) with intestinal failure who have been receiving stable long-term parenteral support (at least 6 months prior to screening and ≥3 times per week) and who can provide consent are the intended participants.

Not a fit: Patients taking certain liver-affecting (steatogenic) medications, those with active systemic illness affecting liver measurements, or patients who can maintain adequate oral or enteral nutrition are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, choline chloride injections could correct choline deficiency and reduce liver injury in patients on long-term parenteral support, improving liver function and nutritional status.

How similar studies have performed: Small studies and case reports suggest parenteral choline can correct deficiency and improve liver markers, but large randomized, placebo-controlled trials in this setting are limited.

Eligibility criteria

Key Inclusion Criteria:

* Male or female 12 years of age or older at the time of signing the informed consent
* Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements, prior to study entry
* Individuals with intestinal failure receiving long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated who are receiving stable PS at time of screening and for the duration of the study; Note: Long-Term PS = Participant must have been receiving PS for at least 6 months prior to screening and requiring PS at least 3 times per week
* Females of childbearing potential must have a negative urine pregnancy test at screening

Key Exclusion Criteria:

* Patients taking steatogenic medications for ≥ 12 weeks in the past 12 months; those taking any medicine that could affect the measurement of hepatic steatosis within 12 weeks prior to study entry
* Evidence of systemic active infection at the time of dosing
* Participants intending to take non-study drug choline supplements or choline-containing multivitamins during the course of the study
* Participants unwilling to limit alcohol intake to no more than 20/g a day for 24 hours prior to their screening visit and for the duration of the study
* Active malignancy (excluding basal cell skin tumor, low or very low risk prostate cancer, cervical carcinoma in situ and local resected cervical cancer)
* Clinically significant renal disease
* Low B12 or low serum folic acid levels that are less than the normal range
* Fulminant liver failure, with active bleeding and/or encephalopathy

Where this trial is running

Aurora, Colorado and 13 other locations

• University of Colorado School of Medicine — Aurora, Colorado, United States (Recruiting)
• Columbia University Medical Center/ New York Presbyterian Hospital — New York, New York, United States (Not_yet_recruiting)
• Duke Clinic - Abdominal Transplant Research Office — Durham, North Carolina, United States (Recruiting)
• Cleveland Clinic — Cleveland, Ohio, United States (Recruiting)
• University Hospitals Leuven, Campus Gasthuisberg — Leuven, Belgium (Not_yet_recruiting)
• Aalborg University Hospital, Department of Medical Gastroenterology — Aalborg, Denmark (Not_yet_recruiting)
• Rigshospitalet - University Hospital Copenhagen — Copenhagen, Denmark (Recruiting)
• Beaujon Hospital - APHP — Clichy, France (Not_yet_recruiting)
• Rennes University Hospital Center - Pontchaillou Site — Rennes, France (Not_yet_recruiting)
• CHRU Nancy - Barbois Hospital — Vandœuvre-lès-Nancy, France (Not_yet_recruiting)
• Charite - University Hospital Berlin — Berlin, Germany (Not_yet_recruiting)
• University Duisburg-Essen, University Hospital Essen — Essen, Germany (Not_yet_recruiting)
• M. Pirogow Provincial Specialized Hospital in Lodz, Nutritional Treatment Center — Lodz, Poland (Not_yet_recruiting)
• Czerniakowski Hospital Sp. z o.o. (LCC) — Warsaw, Poland (Recruiting)

Study contacts

• Study coordinator: Chief Scientific Operations Officer

Conditions Choline Deficiency; Liver Injury; Intestinal Failure; Parenteral Nutrition; Parenteral Support; Choline Chloride; choline deficiency