Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

People with SLOS have a deficiency of the 7-dehydrocholesterol reductase enzyme that makes cholesterol. Consequently, they exhibit deficient cholesterol levels and increased cholesterol precursor lipids, which are thought to be toxic. Cholesterol itself normally regulates the cholesterol synthesis pathway in the body and under conditions of low cholesterol seen in SLOS, more of the toxic cholesterol precursors are made. Since cholesterol is also necessary for production of bile acids in the liver, which help digest dietary cholesterol from the intestine, it is likely that low cholesterol levels in SLOS impairs bile acids from being made, which in turn prevents dietary cholesterol from being absorbed properly and contributes to the cholesterol deficiency seen in SLOS. Raising cholesterol in SLOS people by improving its absorption from the diet is expected to decrease the potentially toxic cholesterol precursor lipids, and both changes would be theoretically beneficial for SLOS people. The objective of this study is to determine whether treatment with cholic acid (a major bile acid made in the body that improves fat absorption) will increase dietary absorption of cholesterol, reverse plasma cholesterol deficiency, and reduce harmful cholesterol precursor lipids. These changes would be favorable for SLOS people. To accomplish this objective, SLOS participants will be given dietary cholic acid (brand name Cholbam, manufactured by Retrophin) for 8 weeks and plasma cholesterol and its precursor lipids will be measured before and while taking the drug. SLOS participants who are between 2 years and 25 years of age and are taking supplemental dietary cholesterol for at least 3 months will be enrolled. Participants must be clinically stable and able to travel to a study site. No change in supplemental dietary cholesterol intake will be allowed during the study, and dietary records will be obtained throughout the study. To qualify for cholic acid therapy, participants must have plasma cholesterol ≤125 mg/dl before starting cholic acid. Participants will be treated with cholic acid for 8 weeks and will have blood specimens drawn at baseline (day 0), 4-weeks, 8-weeks and 12 weeks (4 weeks after stopping cholic acid therapy). ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03720990
Study type Interventional
Source University of Nebraska
Contact
Status Completed
Phase Phase 1/Phase 2
Start date March 27, 2021
Completion date September 30, 2023

See also
  Status Clinical Trial Phase
Terminated NCT01434745 - SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation N/A
Completed NCT00001721 - Study of Smith-Lemli-Opitz Syndrome
Recruiting NCT05687474 - Baby Detect : Genomic Newborn Screening
Enrolling by invitation NCT03655223 - Early Check: Expanded Screening in Newborns
Recruiting NCT00004347 - Phase II Study of Dietary Cholesterol for Smith-Lemli-Opitz Syndrome Phase 2
Completed NCT00114634 - Short-term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome Phase 2
Completed NCT00017732 - Estimation of the Carrier Frequency and Incidence of Smith-Lemli-Opitz Syndrome in African Americans N/A
Completed NCT00064792 - Simvastatin Therapy in Smith-Lemli-Opitz Syndrome Phase 2
Recruiting NCT05642221 - Functional Near-Infrared Spectroscopy (fNIRS) Combined With Diffuse Correlation Spectroscopy (DCS) in Neurocognitive Disease as Compared to Healthy Neurotypical Controls
Terminated NCT01356420 - Sterol and Isoprenoid Disease Research Consortium: Smith-Lemli-Opitz Syndrome N/A
Completed NCT00272844 - Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome Phase 1/Phase 2
Recruiting NCT01773278 - Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS) Phase 2
Completed NCT00070850 - Prenatal Screening For Smith-Lemli-Opitz Syndrome Phase 2