Trial Outcomes & Findings for Simvastatin Therapy in Smith-Lemli-Opitz Syndrome (NCT NCT00064792)

NCT ID: NCT00064792

Last Updated: 2014-06-06

Results Overview

Total serum cholesterol (mg/dL) divided by the sum of all sterols (cholesterol plus its precursors, 7-dehydrocholesterol - 7DHC, and 8-dehydrocholesterol- 8DHC - in mg/dL).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: 1 year after therapy.
• Results posted on: 2014-06-06

Participant Flow

23 subjects were consented and enrolled. 18 of 23 completed both arms of the study.

Each arm of the trial (placebo then simvastatin or simvastatin then placebo) was 12 months in length. The wash out period between phases was 2 months. Each subject served as own control.

Participant milestones

Measure	Placebo Followed by Simvastatin Subjects maintained cholesterol intake of 150mg/kg/day for 12 months. After a 2 month wash out period, they then received Simvastatin 1mg/kg/day (after starting at 0.5mg/kg/day for 6 weeks) in addition to cholesterol.	Simvastatin Followed by Placebo Subjects first received Simvastatin (1mg/kg/day after starting at 0.5mg/kg/day for 6 weeks) in addition to cholesterol 150mg/kg/day for 12 months. After a 2 month wash out period, they then continued with cholesterol supplementation only.
Overall Study STARTED	13	10
Overall Study COMPLETED	8	10
Overall Study NOT COMPLETED	5	0

Reasons for withdrawal

Measure	Placebo Followed by Simvastatin Subjects maintained cholesterol intake of 150mg/kg/day for 12 months. After a 2 month wash out period, they then received Simvastatin 1mg/kg/day (after starting at 0.5mg/kg/day for 6 weeks) in addition to cholesterol.	Simvastatin Followed by Placebo Subjects first received Simvastatin (1mg/kg/day after starting at 0.5mg/kg/day for 6 weeks) in addition to cholesterol 150mg/kg/day for 12 months. After a 2 month wash out period, they then continued with cholesterol supplementation only.
Overall Study Withdrawal by Subject	2	0
Overall Study Adverse Event	3	0

Baseline Characteristics

Simvastatin Therapy in Smith-Lemli-Opitz Syndrome

Baseline characteristics by cohort

Measure	Placebo Followed by Simvastatin n=13 Participants During the placebo phase, subjects were given a daily dose of an oral suspension not containing active drug. All subjects continued taking cholesterol suspension at 150mg/kg/day.	Simvastatin Followed by Placebo n=10 Participants Subjects began this phase by taking 0.5mg/kg/day of an oral suspension with active drug for 6 weeks followed by a daily dose of 1mg/kg/day. Subjects continued taking 150mg/kg/day of cholesterol suspension.	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	8.576388889 years STANDARD_DEVIATION 4.464005643 • n=5 Participants	7.775 years STANDARD_DEVIATION 2.286247802 • n=7 Participants	8.175694444 years STANDARD_DEVIATION 3.58400024 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	10 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year after therapy.

Population: The number of participants was determined by the total number of participants to complete both phases of the trial (n=18).

Total serum cholesterol (mg/dL) divided by the sum of all sterols (cholesterol plus its precursors, 7-dehydrocholesterol - 7DHC, and 8-dehydrocholesterol- 8DHC - in mg/dL).

Outcome measures

Measure	Not Simvastatin n=18 Participants During the placebo phase, subjects were given a daily dose of an oral suspension (OraPlus) not containing active drug. All subjects continued taking cholesterol suspension at 150mg/kg/day.	Simvastatin n=18 Participants Subjects began this phase by taking 0.5mg/kg/day of an oral suspension with active drug for 6 weeks followed by a daily dose of 1mg/kg/day. Subjects continued taking 150mg/kg/day of cholesterol suspension.
Serum Cholesterol to Total Sterol Ratio	90.82 percent total cholesterol Standard Deviation 8.52	93.99 percent total cholesterol Standard Deviation 5.36

SECONDARY outcome

Timeframe: 12 months

Percent of 7-dehydrocholesterol + 8-dehydrocholesterol as a fraction of the total sterols (cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol measured in cerebral spinal fluid

Outcome measures

Measure	Not Simvastatin n=18 Participants During the placebo phase, subjects were given a daily dose of an oral suspension (OraPlus) not containing active drug. All subjects continued taking cholesterol suspension at 150mg/kg/day.	Simvastatin n=18 Participants Subjects began this phase by taking 0.5mg/kg/day of an oral suspension with active drug for 6 weeks followed by a daily dose of 1mg/kg/day. Subjects continued taking 150mg/kg/day of cholesterol suspension.
Cerebral Spinal Fluid Dehydrocholesterol to Total Sterol Ratio	5.898 percent of total sterols Standard Deviation 4.684	5.154 percent of total sterols Standard Deviation 3.067

Adverse Events

OraPlus

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Simvastatin Susp

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	OraPlus n=23 participants at risk During the placebo phase, subjects were given a daily dose of an oral suspension not containing active drug. All subjects continued taking cholesterol suspension at 150mg/kg/day.	Simvastatin Susp n=23 participants at risk Subjects began this phase by taking 0.5mg/kg/day of an oral suspension with active drug for 6 weeks followed by a daily dose of 1mg/kg/day. Subjects continued taking 150mg/kg/day of cholesterol suspension.
Musculoskeletal and connective tissue disorders Muscle Pain and Elevated CK	4.3% 1/23 • Number of events 1 • 6 weeks muscle pain, elevated CK	0.00% 0/10 • 6 weeks muscle pain, elevated CK

Other adverse events

Adverse event data not reported

Additional Information

Dr. Forbes Porter, Clinical Director, NICHD

NICHD, NIH

Phone: 301-435-4432

Email: fdporter@mail.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place