CompletedNCT00227266Updated Mar 19, 2025Results posted

Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy

A Phase 2 interventional study of Valproic Acid and Levocarnitine and Placebo in Spinal Muscular Atrophy, sponsored by University of Utah. Completed at 6 sites in 2 countries. Open to participants aged 2 Years to 17 Years. Per ClinicalTrials.gov, last updated 2025-03-19.

Sponsored by University of Utah · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 94
Allocation: Randomized
Ages: 2 Years to 17 Years
Sex: All

Study summary

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.

Read the 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.

Conditions studied

Spinal Muscular Atrophy

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Keywords

Spinal Muscular Atrophy (SMA)
SMA Type 2
SMA Type 3

In context

Muscular Atrophy

494 studies on the registry are indexed under Muscular Atrophy; 94 are open to participants now.

This study's enrollment of 94 is above the median of 33 across 335 interventional studies indexed under Muscular Atrophy.

Browse Muscular Atrophy studies →

Lead sponsor

University of Utah is the lead sponsor of 969 studies on the registry; 178 are open to participants now.

Of its 107 completed or terminated interventional studies of FDA-regulated products, 62 (58%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 2 Years to 17 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 94 participants (actual)

Study arms

Placebo comparator
Cohort 1a
Patients in Cohort 1a - Placebo Comparator, will be on a placebo for 6 months and then will switch to the active treatment. Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor or equivalent placebo in the liquid form.
Drug: Valproic Acid and Levocarnitine · Drug: Placebo
Active comparator
Cohort 1b
Cohort 1b - Active Comparator will be on treatment throughout the study. Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor in the liquid form.
Drug: Valproic Acid and Levocarnitine
Experimental
Cohort 2
Cohort 2 pts are on open-label treatment throughout. Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor or equivalent placebo in the liquid form.
Drug: Valproic Acid and Levocarnitine

Interventions

DrugValproic Acid and Levocarnitine
VPA,sprinkle cap; Levocarnitine, syrup; dosage is by weight
Also known as: Depakote, VPA, Carnitor
DrugPlacebo

What researchers measure

Primary outcomes

Safety Labs
Participants will have labs drawn regularly to maintain appropriate dosing and monitor liver function
Time frame: -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs
Efficacy, Measured Through Motor Function Assessments
Time frame: -4wks, 0, 3 mo, 6 mo, 12 mo
Modified Hammersmith Change From Baseline to 6 Months
Comparison of Modified Hammersmith Change from baseline to 6 months. Scores range from 0 to 40. A higher score indicates a better outcome. This scale is used to assess gross motor abilities of non-ambulant children with SMA in multiple research trials as well as in clinical settings.
Time frame: 0 months, 6 months

Secondary outcomes

Quantitative Assessment of SMN mRNA From Blood Samples
Time frame: -4wks or 0, 3 mo, 6 mo, 12 mo
Peds QL™ Assessment: Parental Version (All), Child Versions (> 5yrs)
Time frame: -4wks, 0, 3mo, 6mo, 12mo
Max CMAP Amplitude (Mean)
The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed.
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
The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed.
Time frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
Ulnar MUNE
Time frame: -4 wks, 0, 3 mo, 6 mo, 12 mo
Growth and Vital Sign Parameters
Time frame: -4 wks, 0, 3mo, 6mo, 12mo
Nutritional Status
Time frame: -4 wks, 0, 3mo, 6mo, 12mo
DEXA
Time frame: 0, 6mo, 12mo
Max CMAP Area (Mean)
The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve.
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)
The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve.
Time frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)

Results

Posted May 3, 2011

Participant flow

Subject's were recruited during the periods of September 2005 to September 2006 across the United States.

Participant flow — Overall Study
Milestone	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment
Started	31	30	33
Completed	30	30	29
Not completed	1	0	4
Withdrew: Withdrawal by subject	0	0	1
Withdrew: Protocol violation	1	0	1
Withdrew: Excessive weight gain	0	0	2

Outcome measures

PrimarySafety Labs

Participants will have labs drawn regularly to maintain appropriate dosing and monitor liver function

Time frame:: -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs

Results for this outcome have not been posted.

PrimaryEfficacy, Measured Through Motor Function Assessments

Time frame:: -4wks, 0, 3 mo, 6 mo, 12 mo

Results for this outcome have not been posted.

SecondaryQuantitative Assessment of SMN mRNA From Blood Samples

Time frame:: -4wks or 0, 3 mo, 6 mo, 12 mo

Results for this outcome have not been posted.

SecondaryPeds QL™ Assessment: Parental Version (All), Child Versions (> 5yrs)

Time frame:: -4wks, 0, 3mo, 6mo, 12mo

Results for this outcome have not been posted.

SecondaryMax CMAP Amplitude (Mean)

The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed.

Time frame:: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
Reported as:: Mean · mV

Max CMAP Amplitude (Mean)
mV	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment
Baseline	2.28 ± 1.55	2.93 ± 1.56	5.52 ± 2.56
6 months	2.32 ± 1.75	2.37 ± 1.82	6.56 ± 2.99

SecondaryMax CMAP Amplitude Median

Time frame:: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
Reported as:: Median · mV

Max CMAP Amplitude Median
mV	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment
Baseline	1.91 (0.5 to 7.66)	2.2 (0.5 to 6.66)	5.3 (1.2 to 10.42)
6 months	1.44 (0.5 to 6.14)	1.8 (0.3 to 7.81)	5.85 (1.50 to 12.20)

SecondaryUlnar MUNE

Time frame:: -4 wks, 0, 3 mo, 6 mo, 12 mo

Results for this outcome have not been posted.

SecondaryGrowth and Vital Sign Parameters

Time frame:: -4 wks, 0, 3mo, 6mo, 12mo

Results for this outcome have not been posted.

SecondaryNutritional Status

Time frame:: -4 wks, 0, 3mo, 6mo, 12mo

Results for this outcome have not been posted.

Post-hocModified Hammersmith Extend Baseline

Baseline Modified Hammersmith Extend testing. The baseline test is the score they receive during their screening visits. This scale ranges from 0 to 56. A higher score indicates a better outcome. This scale is used to assess gross motor abilities of children with SMA in multiple research trials as well as in clinical settings.

Time frame:: 1 month prior to enrollment, at enrollment (0 months)
Reported as:: Mean · Score

Modified Hammersmith Extend Baseline
Score	Cohort 2 Experimental
Modified Hammersmith Extend at S1 (-4 weeks)	47.0 (29 to 56)
Modified Hammersmith Extend at S2 (0 weeks)	48.3 (36 to 56)

Statistical analysis

Cohort 2 Experimental · Spearman's correlation · p = <0.001 · Spearman's correlation: 0.93

PrimaryModified Hammersmith Change From Baseline to 6 Months

Comparison of Modified Hammersmith Change from baseline to 6 months. Scores range from 0 to 40. A higher score indicates a better outcome. This scale is used to assess gross motor abilities of non-ambulant children with SMA in multiple research trials as well as in clinical settings.

Time frame:: 0 months, 6 months
Reported as:: Mean · Score

Modified Hammersmith Change From Baseline to 6 Months
Score	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment
Baseline visit (0 weeks)	20.0 ± 9.3	16.6 ± 8.7
6 Month visit (V2)	20.6 ± 8.1	16.8 ± 7.9
Change from Baseline	0.6 ± 3.98	0.2 ± 2.88

SecondaryDEXA

Time frame:: 0, 6mo, 12mo

Results for this outcome have not been posted.

SecondaryMax CMAP Area (Mean)

The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve.

Time frame:: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
Reported as:: Mean · mVms

Max CMAP Area (Mean)
mVms	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment
Baseline	5.46 ± 5.03	5.45 ± 4.23	14.85 ± 7.68
6 months	5.28 ± 4.49	5.26 ± 4.65	16.26 ± 7.13

SecondaryMax CMAP Area (Median)

Time frame:: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
Reported as:: Median · mVms

Max CMAP Area (Median)
mVms	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment
Baseline	3.6 (0.7 to 19.71)	4.6 (1.3 to 16.78)	13.65 (2.6 to 38.29)
6 months	3.74 (0.6 to 16.13)	3.4 (0.6 to 18.81)	16.85 (3.7 to 29.10)

Adverse events

Collected over Phase 1 Serious Adverse Events (time period during which placebo (1a) and treatment (1b)were randomly treated): 6 months. And Phase 1 and 2 Adverse Events: 12 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort 1a Sitters Placebo Then Treatment	—	1/31 (3.2%)	18/31 (58.1%)
Cohort 1b Sitters Treatment	—	4/30 (13.3%)	23/30 (76.7%)
Cohort 2 Standers and Walkers - Treatment	—	4/33 (12.1%)	28/33 (84.8%)

Most frequent serious events

Most frequent serious events
Event	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment
PneumoniaRespiratory, thoracic and mediastinal disorders	0/31	2/30	1/33
DiarrheaGastrointestinal disorders	0/31	0/30	2/33
CoughRespiratory, thoracic and mediastinal disorders	0/31	1/30	0/33
DehydrationMetabolism and nutrition disorders	0/31	1/30	0/33
General DisorderGeneral disorders	0/31	1/30	0/33
PneumonitisInfections and infestations	0/31	1/30	0/33
TachyponeaRespiratory, thoracic and mediastinal disorders	0/31	1/30	1/33
VomitingGastrointestinal disorders	0/31	1/30	1/33
Upper respiratory infectionInfections and infestations	1/31	0/30	1/33
Skin RashSkin and subcutaneous tissue disorders	0/31	0/30	1/33

Most frequent other events

Showing 10 of 56

Most frequent other events
Event	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment
VomitingGastrointestinal disorders	6/31	12/30	6/33
CoughRespiratory, thoracic and mediastinal disorders	2/31	7/30	4/33
Abdominal Pain UpperGastrointestinal disorders	2/31	3/30	7/33
PyrexiaGeneral disorders	4/31	5/30	7/33
PneumoniaRespiratory, thoracic and mediastinal disorders	2/31	6/30	2/33
Multiple AllergiesImmune system disorders	0/31	2/30	5/33
NauseaGastrointestinal disorders	2/31	4/30	2/33
Weight IncresedInvestigations	4/31	3/30	0/33
Ear InfectionInfections and infestations	2/31	3/30	4/33
NasopharyngitisInfections and infestations	3/31	3/30	0/33

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment	Total
<=18 years	31	30	33	94
Between 18 and 65 years	0	0	0	0
>=65 years	0	0	0	0

Age, Continuous
Age, Continuous(years)	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment	Total
Mean	4.4 ± 1.9	4.3 ± 2.1	7.3 ± 3.7	5.4 ± 3.0

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment	Total
Female	11	17	11	39
Male	20	13	22	55

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment	Total
Hispanic or Latino	2	1	0	3
Not Hispanic or Latino	29	27	30	86
Unknown or Not Reported	0	2	3	5

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment	Total
American Indian or Alaska Native	0	0	0	0
Asian	1	2	1	4
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	1	0	0	1
White	26	25	29	80
More than one race	0	0	0	0
Unknown or Not Reported	3	3	3	9

Region of Enrollment
Region of Enrollment(participants)	Cohort 1a Sitters Placebo Then Treatment	Cohort 1b Sitters Treatment	Cohort 2 Standers and Walkers - Treatment	Total
United States	25	26	29	80
Canada	6	4	4	14

Study locations

6 sites

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

References and documents

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Kissel JT, Scott CB, Reyna SP, Crawford TO, Simard LR, Krosschell KJ, Acsadi G, Elsheik B, Schroth MK, D'Anjou G, LaSalle B, Prior TW, Sorenson S, Maczulski JA, Bromberg MB, Chan GM, Swoboda KJ; Project Cure Spinal Muscular Atrophy Investigators' Network. SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy. PLoS One. 2011;6(7):e21296. doi: 10.1371/journal.pone.0021296. Epub 2011 Jul 6. PubMed 21754985 ↗
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Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 19, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00227266
Lead sponsor: University of Utah
Collaborators: Families of Spinal Muscular Atrophy, Leadiant Biosciences, Inc., Abbott
Responsible party: Sponsor
First posted: Sep 27, 2005
Start date: Sep 2005
Primary completion: Nov 2007
Completion: Nov 2007
Results posted: May 3, 2011
Last update: Mar 19, 2025

Study contacts

Kathryn J Swoboda, M.D.

principal investigator · University of Utah/Primary Children's Medical Center

Oversight

Data monitoring committee: Yes

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Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy

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