Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy

Condition(s) targeted: Spinal Muscular Atrophy

Intervention: Valproic Acid and Levocarnitine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: University of Utah

Official(s) and/or principal investigator(s):
Kathryn J Swoboda, M.D., Principal Investigator, Affiliation: University of Utah/Primary Children's Medical Center

This is a multi-center trial to assess safety and efficacy of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat

protocol for SMA "sitters" 2 - 8 years of age. Cohort 2 is an open label protocol for SMA

"standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes.

Outcome measures will include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.

Official title: Multi-Center Phase II Trial of Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy (SMA CARNI-VAL Trial)

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study

Primary outcome:

Safety (including Tolerability), measured through safety labs and parent reports

Efficacy, measured through motor function assessments

Secondary outcome:

Quantitative assessment of SMN mRNA from blood samples

Peds QL™ assessment: parental version (all), child versions (> 5yrs)

Max CMAP amplitude/area

Ulnar MUNE

Growth and vital sign parameters

Nutritional Status

DEXA

Pulmonary Function for pts 5 years+

Detailed description: This is a multi-center phase II trial of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a

double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 -

8 years of age. Subjects will undergo two baseline assessments over 4 to 6 week period, then will be randomized to treatment or placebo for the next six months. All subjects will then be placed on active treatment for the subsequent six month period. Cohort 2 is an open label

protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of

efficacy outcomes. Subjects will undergo two baseline assessments over a four to six week period, followed by one year active treatment with VPA and carnitine. Outcome measures are performed every 3 to 6 months, and include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.

Minimum age: 2 Years. Maximum age: 17 Years. Gender(s): Both.

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.

Johns Hopkins University, Baltimore, Maryland 21287, United States

Children's Hospital of Michigan, Detroit, Michigan 48201, United States

Ohio State University, Columbus, Ohio 43210-1228, United States

Hospital Sainte-Justine, Montreal, Quebec H3T 1C5, Canada

University of Utah/Primary Children's Medical Center, Salt Lake City, Utah 84132, United States

University of Wisconsin Children's Hospital, Madison, Wisconsin 53792-9988, United States

"Click here for more information about this study"

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Starting date: September 2005
Ending date: November 2007
Last updated: December 23, 2007