GlycoCholic Acid Treatment for Patients With Inborn Errors in Bile Acid Synthesis

NCT01589523 | Completed Phase 3 Results

• 1 other identifier: 2009-0780
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the way (mechanisms) by which your defect in bile acid handling (metabolism) causes your liver disease or abnormality in absorption of vitamins and the effect of an investigational bile acid therapy (glycocholic acid) on your vitamin absorption and your liver disease. An investigational therapy is one that not approved by the United States Food and Drug Administration (FDA) and is being provided to you under an Investigational New Drug application from the FDA.

Conditions

Bile Acid Synthesis Defect; Inborn Error of Bile Acid Metabolism; Inborn Error of Bile Acid Conjugation

Outcome Measures

Primary Outcomes (2)

• Conjugated Cholic Acid (GCA) for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-chain Conjugation.

  This is the number of participants with bile acid amidation defects treated with oral glycocholic acid (15 milligrams/kilograms (mg/kg) of body weight/day (bw/day))

  Up to 10 years

• Evaluation of Levels of Atypical Bile Acid Metabolites After GCA Treatment Compared

  Semi-quantitative descriptive evaluation of the levels of atypical bile acids in urine measured by mass spectrometry (FAB MS) based on a scale of 0 = absent or traces levels, 1 = low levels, 2 = moderate levels, 3 = high levels using the signal/noise ratio and intensity of ions. Atypical bile acids evaluated included m/z 407 (unconjugated cholic acid), m/z 471 (dihydroxy-choleanoic-sulfate) and m/z 583 (trihydroxy-choleanoic glucuronide).

  Average of 6 months, average 12 months, and average of after year 1 to 10 years

Secondary Outcomes (3)

• Changes in Liver Function Tests of ALT From Baseline to Post-treatment

  Comparison between baseline and post-treatment (average of available timepoints after year 1 through year 10)

• Change in Liver Function Test: AST From Baseline to Post-treatment

  Comparison between baseline and post-treatment (average of available timepoints after year 1 through year 10)

• Change in Vitamin D, 25-OH Measure From Baseline to Post-treatment

  Pre-treatment and post treatment (average of available timepoints after year 1 through year 10)

Study Arms (1)

GlycoCholic Acid, Study Drug

EXPERIMENTAL

An open label, single arm, non-randomized, non-comparative, treatment study of Glycocholic Acid in the treatment of defects of bile acid metabolism.

Drug: Glycocholic Acid

Interventions

Glycocholic Acid DRUG

10-15mg/kg body weight/day taken orally. Supplied as either liquid or 50mg capsules.

Also known as: Conjugated Cholic Acid

GlycoCholic Acid, Study Drug

Eligibility Criteria

• Age: 1 Week - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmation of a diagnosis of an inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.
• Any age
• Participant must be willing and able to comply with study assessments and procedures.
• The participant and/or parent/legal guardian must have signed the written informed consent document prior to study start.

You may not qualify if:

• \. No confirmed diagnosis of inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (2)

• Setchell KD, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edreesi M, Potter C, Russell DW, O'Connell NC, Wolfe B, Jha P, Zhang W, Bove KE, Knisely AS, Hofmann AF, Rosenthal P, Bull LN. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology. 2013 May;144(5):945-955.e6; quiz e14-5. doi: 10.1053/j.gastro.2013.02.004. Epub 2013 Feb 13.

  PMID: 23415802 RESULT

• Heubi JE, Setchell KD, Jha P, Buckley D, Zhang W, Rosenthal P, Potter C, Horslen S, Suskind D. Treatment of bile acid amidation defects with glycocholic acid. Hepatology. 2015 Jan;61(1):268-74. doi: 10.1002/hep.27401. Epub 2014 Dec 23.

  PMID: 25163551 RESULT

MeSH Terms

Interventions

Glycocholic Acid

Intervention Hierarchy (Ancestors)

Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; N-substituted Glycines; Glycine; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Ken Setchell, PhD
• Organization: Cincinnati Children's Hospital Medical Center

kenneth.setchell@cchmc.org

5136364548

Study Officials

• Kenneth D. Setchell, Ph.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• James E. Heubi, M.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2012
• First Posted: May 2, 2012
• Study Start: February 1, 2006
• Primary Completion: January 22, 2019
• Study Completion: January 22, 2019
• Last Updated: June 8, 2022
• Results First Posted: May 12, 2022

Record last verified: 2022-05

Locations

US (1)