Smith-Lemli-Opitz Syndrome and Cholic Acid
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03720990|
Recruitment Status : Not yet recruiting
First Posted : October 26, 2018
Last Update Posted : October 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Smith-Lemli-Opitz Syndrome||Drug: Cholic Acid||Phase 1 Phase 2|
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 serum 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 serum 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 serum 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 serum 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 two measurements of serum cholesterol ≤100 mg/dl within one month 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Smith-Lemli-Opitz Syndrome: A Pilot Study of Cholic Acid Supplementation|
|Estimated Study Start Date :||November 1, 2019|
|Estimated Primary Completion Date :||April 1, 2020|
|Estimated Study Completion Date :||April 1, 2020|
Experimental: Cholic acid
Participants will be treated with cholic acid 10 mg/kg body weight.
Drug: Cholic Acid
Participants will be treated with cholic acid for 8 weeks
Other Name: Cholbam
- Change in Serum Cholesterol and Cholesterol Metabolites [ Time Frame: From enrollment to end of 8 weeks on cholic acid treatment ]Serum cholesterol will be measured along with 7-dehydrocholesterol, 8-dehydrocholesterol and oxysterols. Response to cholic acid treatment will consist of an increase in serum cholesterol and/or decrease in 7-dehydrocholesterol, 8-dehydrocholesterol and oxysterols.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03720990
|Contact: Ellen R Elias, MD||720-777-5401||Ellen.firstname.lastname@example.org|
|Contact: Sara M Jones, RD||402-559-1747||SaraM.Jones@unmc.edu|
|United States, Colorado|
|Colorado Children's Hospital||Not yet recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Ellen R Elias, MD 720-777-5401 Ellen.email@example.com|
|Contact: Michelle Lowary, MS (720) 777-8485 firstname.lastname@example.org|
|United States, Nebraska|
|University of Nebraska Medical Center||Not yet recruiting|
|Omaha, Nebraska, United States, 68198|
|Contact: Sara M Jones, RD 402-559-1747 SaraM.Jones@unmc.edu|
|Contact: William B Rizzo, MD 402-559-2560 email@example.com|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Not yet recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: James E. Heubi, MD 513-636-4415 James.Heubi@cchmc.org|
|Contact: Andre Hawkins, M.A. (513) 636-4200 firstname.lastname@example.org|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh||Not yet recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Gerard Vockley, MD 412-692-7746 Gerard.Vockley@chp.edu|
|Contact: Danielle Black 412-692-3150 Danielle.Black@chp.edu|
|Study Chair:||Ellen R Elias, MD||University of Colorado - Colorado Children's Hospital|
|Principal Investigator:||William B Rizzo, MD||University of Nebraska|