Future Study for Patients with SLOS: - PowerPoint Presentation

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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

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

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

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

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

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

Enrollment Criteria ContinuedPatients 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

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.

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.

Timing of StudyWe hope that this study will begin in late 2017.

Future plansIf 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