Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00227266
• Date of registration: 23/09/2005
• Primary sponsor: University of Utah
• Public title: Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy
• Scientific title: Multi-center Phase II Trial of Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy (SMA CARNI-VAL Trial)
• Date of first enrolment: September 2005
• Target sample size: 94
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00227266
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Countries of recruitment

Canada, United States

Contacts

• Name: Kathryn J Swoboda, M.D.
• Affiliation: University of Utah/Primary Children's Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

Cohort 1

- Confirmed genetic diagnosis of 5q SMA

- SMA 2 or non-ambulatory SMA 3: all subjects must be able to sit independently for at
least 3 seconds without support

- Age 2 to 8 years at time of enrollment

Cohort 2

- Confirmed genetic diagnosis of 5q SMA

- SMA subjects (SMA types 2 or 3) who can stand independently without braces or other
support for up to 2 seconds, or walk independently

- Age 3 to 17 years at time of study enrollment

Exclusion Criteria:

Cohort 1

- Need for BiPAP support > 12 hours per day

- Spinal rod or fixation for scoliosis or anticipated need within six months of
enrollment

- Inability to meet study visit requirements or cooperate reliably with functional
testing

- Coexisting medical conditions that contraindicate travel, testing or study
medications

- Use of medications or supplements which interfere with valproic acid or carnitine
metabolism within 3 months of study enrollment.

- Current use of either VPA or carnitine. If study subject is taking VPA or carnitine
then patient must go through a washout period of 12 weeks before enrollment into the
study

- Body Mass Index > 90th % for age

Cohort 2

- Spinal rod or fixation for scoliosis or anticipated need within six months of
enrollment

- Inability to meet study visit requirements or cooperate with functional testing

- Transaminases, amylase or lipase > 3.0 x normal values, WBC < 3.0 or neutropenia <
1.0, platelets < 100 K, or hematocrit < 30 persisting over a 30 day period.

- Coexisting medical conditions that contraindicate travel, testing or study
medications

- Use of medications or supplements which interfere with valproic acid or carnitine
metabolism within 3 months of study enrollment.

- Current use of either VPA or carnitine. If study subject is taking VPA or carnitine
then patient must be go through a washout period of 12 weeks before enrollment in the
study.

- Body Mass Index > 90th % for age

- Pregnant women/girls, or those intending to try to become pregnant during the course
of the study.



Age minimum: 2 Years
Age maximum: 17 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy

Intervention(s)

Drug: Placebo

Drug: Valproic Acid and Levocarnitine

Primary Outcome(s)

Efficacy, Measured Through Motor Function Assessments [Time Frame: -4wks, 0, 3 mo, 6 mo, 12 mo]

Modified Hammersmith Change From Baseline to 6 Months [Time Frame: 0 months, 6 months]

Safety Labs [Time Frame: -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs]

Secondary Outcome(s)

DEXA [Time Frame: 0, 6mo, 12mo]

Growth and Vital Sign Parameters [Time Frame: -4 wks, 0, 3mo, 6mo, 12mo]

Max CMAP Amplitude (Mean) [Time Frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)]

Max CMAP Amplitude Median [Time Frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)]

Max CMAP Area (Mean) [Time Frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)]

Max CMAP Area (Median) [Time Frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)]

Nutritional Status [Time Frame: -4 wks, 0, 3mo, 6mo, 12mo]

Peds QL™ Assessment: Parental Version (All), Child Versions (> 5yrs) [Time Frame: -4wks, 0, 3mo, 6mo, 12mo]

Quantitative Assessment of SMN mRNA From Blood Samples [Time Frame: -4wks or 0, 3 mo, 6 mo, 12 mo]

Ulnar MUNE [Time Frame: -4 wks, 0, 3 mo, 6 mo, 12 mo]

Secondary ID(s)

13698

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Abbott

Families of Spinal Muscular Atrophy

Sigma Tau Pharmaceuticals, Inc.