Smith-Lemli-Opitz Syndrome and Cholic Acid
Condition: Smith-Lemli-Opitz Syndrome
MeSH terms: Cleft Palate; Hypertelorism; Hypospadias; Genetic Diseases, X-Linked; Smith-Lemli-Opitz Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Detailed 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).
    

Intervention name(s): Cholic Acid
Intervention type(s): Drug
Intervention description(s): Participants will be treated with cholic acid for 8 weeks
Other intervention name(s): Cholbam
Intervention MeSH terms: Cholic Acids
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: 7-Dehydrocholesterol reductase deficiency