Smith-Lemli-Opitz Syndrome and Cholic Acid

NCT03720990 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 0464-18-FB
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine whether dietary cholic acid therapy benefits people with Smith-Lemli-Opitz syndrome (SLOS) by leading to an increase in plasma cholesterol and reduction in harmful cholesterol precursors. SLOS participants will be treated with dietary cholic acid for 8 weeks and plasma cholesterol and cholesterol precursor metabolites will be measured.

Conditions

Smith-Lemli-Opitz Syndrome

Keywords

7-Dehydrocholesterol reductase deficiency

Outcome Measures

Primary Outcomes (1)

• Change in Plasma Cholesterol

  Plasma cholesterol will be measured. Response to cholic acid treatment will consist of a change in plasma cholesterol.

  8 weeks

Study Arms (1)

Cholic acid

EXPERIMENTAL

Participants will be treated with cholic acid 10 mg/kg body weight.

Drug: Cholic Acid

Interventions

Cholic Acid DRUG

Participants will be treated with cholic acid for 8 weeks

Also known as: Cholbam

Cholic acid

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 2-25 years.
• Participants (or their parents/legally-authorized representative) must provide signed informed consent.
• Assent must be obtained from those participants ages 7-17 years who are intellectually capable of understanding this study.
• Diagnosis of SLOS based on clinical features and biochemical + genetic confirmation.
• Participants are capable of traveling to the STAIR study site.
• Fasting plasma cholesterol ≤125 mg/dL during the Qualification Phase must be established before starting cholic acid therapy.
• Clinically stable at the time of enrollment
• Participants must be on a constant dietary cholesterol intake for at least 3-months prior to treatment with cholic acid.
• Participants must agree to make no changes in cholesterol supplementation during the STAIR study.
• SLOS participants who are taking antioxidants will be included. Participants must agree to make no changes in the antioxidant dose during this study.
• For females of childbearing age (who have begun menstruating), a negative pregnancy test must be documented at the start of the study (week 0/ baseline) and at the end of cholic acid administration (week 8).

You may not qualify if:

• Participants are unable to provide signed informed consent and/or verbal assent.
• Participants have an unstable clinical condition that would prevent completion of the study. Medically unstable participants would include those with severe liver disease, complex birth defects such as severe heart disease or renal dysplasia, those with severe respiratory compromise requiring tracheostomy, or those who are not likely to survive longer than 1 year.
• Participants are taking drugs, nutraceuticals, probiotics or other compounds that are known or suspected to affect sterol metabolism.
• Participants have transaminase elevations (\>3-fold above the reference range) at baseline.

Sponsors & Collaborators

• University of Nebraska: lead
• University of Colorado, Denver: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of Pittsburgh: collaborator

Study Sites (2)

Colorado Children's Hospital

Aurora, Colorado, 80045, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Smith-Lemli-Opitz Syndrome

Interventions

Cholic Acid

Condition Hierarchy (Ancestors)

Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Limitations and Caveats

No limitations or caveats.

Results Point of Contact

• Title: William Rizzo
• Organization: University of Nebraska Medical Center

wrizzo@unmc.edu

402-559-2560

Study Officials

• Ellen R Elias, MD

  University of Colorado - Colorado Children's Hospital

  STUDY CHAIR

• William B Rizzo, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 26, 2018
• Study Start: March 27, 2021
• Primary Completion: August 30, 2022
• Study Completion: September 30, 2023
• Last Updated: April 30, 2024
• Results First Posted: December 13, 2023

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available one year after completion of the study. Data will be available indefinitely.
• Access Criteria: Data will be made available to everyone.

Locations

US (2)