1. Future Study for Patients with SLOS: A Pilot Study of Cholic Acid Supplementation
Ellen Roy Elias, MD Children’s Hospital Colorado
Jean-Baptiste Roullet, PhD Washington State University
WILLIAM RIZZO, MD University of Nebraska

2. Why use bile acids in SLOS patients?
Patients with cholesterol deficiency are not able to make bile acids, which are made from cholesterol. Therefore, patients with severe SLOS have bile acid deficiency
Bile acids are essential for absorption of nutrients in the intestines, particularly fats and fat soluble vitamins
Without sufficient bile acids present in the gut, patients cannot properly absorb cholesterol and other nutrients

3. Bile acids (including one called Cholic acid) were used in the early 1990’s to treat patients with SLOS.
The bile acids were tolerated well and seemed to help cholesterol levels improve on treatment.
But in the late 1990’s, Cholic Acid stopped being manufactured and was not available until recently
A new pharmaceutical company, Retrophin, is manufacturing Cholic acid again, called Cholbam and has offered to make it available for patients with SLOS

4. How will the Cholic Acid Study work?
The study will be part of the STAIR consortium
The initial study will be a PILOT study to evaluate the efficacy and safety of Cholic acid in patients with SLOS.
We will start with about 1 dozen patients with SLOS
We want to show that using Cholic acid helps patients with SLOS to have higher cholesterol levels and lower levels of the precursors 7- DHC and 8-DHC
We will try to determine which doses are best

5. We want to make sure that the Cholic acid does not cause too many side effects such as stomach aches or diarrhea
We will follow blood tests to make sure that the Cholic acid does not have any bad effects

6. What are the enrollment criteria?
Patients must be 2-20 years old
Cholesterol levels < 100 mg/dL
Patients must be stable enough to travel to a STAIR site – if you are already seeing Dr Elias in Colorado, and are eligible for this study, your enrollment could happen at the same time as your visit for the antioxidant study

7. Enrollment Criteria Continued
Patients may take different forms of cholesterol supplementation such as Dr Elias’ suspension, or high cholesterol foods or Cholextra
Patients must stay on the same cholesterol supplementation at the same dose for the duration of the study
Patients may also be taking antioxidants while on this study

8. Study Design:
2 weeks of screening to ensure cholesterol is stable and below 100 mg/dl on 2 separate measurements
8 weeks of treatment with Cholic Acid (Cholbam) either orally or via gastrostomy tube, with 4-week follow-up after the treatment is finished.
Blood will be collected at baseline, week 4, week 8 and week 12.

9. Primary outcomes: serum cholesterol (CHOL) and cholesterol precursors 7- and 8-dehydrocholesterol (7DHC and 8DHC), and the 7DHC + 8DHC/CHOL ratio.
Secondary outcomes: oxysterols , vitamin D, bile acids
Cholbam safety/toxicity will be monitored with liver, kidney tests and blood counts.

10. Timing of Study
We hope that this study will begin in late 2017.

11. Future plans
If Cholbam proves to be effective and safe in this Pilot study, leading to increased cholesterol levels and decreased 7-DHC and 8-DHC, we would like to plan:
Enrolling more patients
Future studies following clinical measures
Treating for longer periods
Consider developing a placebo-controlled trial