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Spinal Muscular AtrophyPhase 1NCT00374075

Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy

A Phase 1 study testing Valproic Acid in people with Spinal Muscular Atrophy, run by University of Utah at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open label phase I/II clinical trial to assess safety, tolerability and potential effect on SMN mRNA and protein in vivo of a compound in which preliminary evidence supports a potential effect on SMN levels in vitro. Read more about this study

Who is it for?
Ages 2 years and older
Conditions the study is for
Spinal Muscular Atrophy
What is being tested?
Valproic Acid
How many people
42 participants
Where
1 siteUnited States
Study dates
Sep 2003to Feb 2006
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must have a diagnosis of SMA, confirmed by genetic testing
  • Only patients 2 years of age and older at enrollment will be eligible

Who cannot join

  • Patients taking any medications with known hepatotoxicity, congenital metabolic disorders or on multiple anticonvulsant medications
  • Patients taking medications which may interact with VPA
  • Patients on ventilatory support for more than 16 hours per day
  • Patients currently enrolled in other treatment trials

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Utah/Primary Children's Medical Center

    Salt Lake City, Utah, 84132

Other trials in United States

About this study

Official title: In Vivo Study of Safety, Tolerability and Dosing Effect on SMN mRNA and Protein Levels of Valproic Acid in Patients With Spinal Muscular Atrophy

This is an open label phase I/II clinical trial to assess safety, tolerability and potential effect on SMN mRNA and protein in vivo of a compound in which preliminary evidence supports a potential effect on SMN levels in vitro.

Read the detailed description

This is an open label phase I/II trial of valproic acid in 40 SMA subjects > 2 years of age with severe, intermediate, and mild phenotypes. Primary outcome measures includes laboratory and physical examination assessments to monitor effects on liver, hematologic, metabolic and nutritional status. Secondary outcomes includes measures of gross motor function; electrophysiologic measures of denervation; DEXA estimates of body composition, bone mineral density and content; measures of pulmonary function; and quantitative SMN mRNA and protein levels in blood cells. Subjects will need 2-3 baseline visits over a 3 -6 month period prior to enrollment. Follow-up visits will be scheduled at 3, 6 and 12 months on treatment.

Being tested
Valproic Acid
Keywords
Spinal Muscular Atrophy (SMA), Valproic Acid
Medical subject headings
Muscular Atrophy, Spinal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Valproic AcidDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To assess safety and tolerability of VPA in SMA patients greater than 2 years of age

Secondary outcomes (5)

  1. To look for a potential in vivo effect of VPA on SMN mRNA in patient blood cells at routinely used clinical doses

  2. Measures of gross motor function

  3. Electrophysiologic measures of denervation

  4. DEXA estimates of body composition, bone mineral density and content

  5. Measures of pulmonary function

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2006 (estimated)
  2. Study startSep 2003
  3. Study completionFeb 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00374075
Sponsor's protocol ID
11893
Status last verified
Aug 2016
First submitted
6 Sep 2006
Last updated
10 May 2023
Results posted
No

Publications

  • Brahe C, Bertini E. Spinal muscular atrophies: recent insights and impact on molecular diagnosis. J Mol Med (Berl). 1996 Oct;74(10):555-62. doi: 10.1007/s001090050059.

    PubMed 8912176

  • Roberts DF, Chavez J, Court SD. The genetic component in child mortality. Arch Dis Child. 1970 Feb;45(239):33-8. doi: 10.1136/adc.45.239.33.

    PubMed 4245389

  • Pearn J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J Med Genet. 1978 Dec;15(6):409-13. doi: 10.1136/jmg.15.6.409.

    PubMed 745211

  • Czeizel A, Hamula J. A hungarian study on Werdnig-Hoffmann disease. J Med Genet. 1989 Dec;26(12):761-3. doi: 10.1136/jmg.26.12.761.

    PubMed 2614795

  • Emery AE. Population frequencies of inherited neuromuscular diseases--a world survey. Neuromuscul Disord. 1991;1(1):19-29. doi: 10.1016/0960-8966(91)90039-u.

    PubMed 1822774

  • Merlini L, Stagni SB, Marri E, Granata C. Epidemiology of neuromuscular disorders in the under-20 population in Bologna Province, Italy. Neuromuscul Disord. 1992;2(3):197-200. doi: 10.1016/0960-8966(92)90006-r.

    PubMed 1483045

  • Pearn J. Classification of spinal muscular atrophies. Lancet. 1980 Apr 26;1(8174):919-22. doi: 10.1016/s0140-6736(80)90847-8.

    PubMed 6103267

  • Bromberg MB, Swoboda KJ. Motor unit number estimation in infants and children with spinal muscular atrophy. Muscle Nerve. 2002 Mar;25(3):445-7. doi: 10.1002/mus.10050.

    PubMed 11870724

  • Swoboda KJ, Prior TW, Scott CB, McNaught TP, Wride MC, Reyna SP, Bromberg MB. Natural history of denervation in SMA: relation to age, SMN2 copy number, and function. Ann Neurol. 2005 May;57(5):704-12. doi: 10.1002/ana.20473.

    PubMed 15852397

  • Crawford TO. From enigmatic to problematic: the new molecular genetics of childhood spinal muscular atrophy. Neurology. 1996 Feb;46(2):335-40. doi: 10.1212/wnl.46.2.335. No abstract available.

    PubMed 8614490

  • Gilliam TC, Brzustowicz LM, Castilla LH, Lehner T, Penchaszadeh GK, Daniels RJ, Byth BC, Knowles J, Hislop JE, Shapira Y, et al. Genetic homogeneity between acute and chronic forms of spinal muscular atrophy. Nature. 1990 Jun 28;345(6278):823-5. doi: 10.1038/345823a0.

    PubMed 1972783

  • Melki J, Lefebvre S, Burglen L, Burlet P, Clermont O, Millasseau P, Reboullet S, Benichou B, Zeviani M, Le Paslier D, et al. De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. Science. 1994 Jun 3;264(5164):1474-7. doi: 10.1126/science.7910982.

    PubMed 7910982

  • Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AH, McPherson JD. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999 Jul;8(7):1177-83. doi: 10.1093/hmg/8.7.1177.

    PubMed 10369862

  • Campbell L, Potter A, Ignatius J, Dubowitz V, Davies K. Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype. Am J Hum Genet. 1997 Jul;61(1):40-50. doi: 10.1086/513886.

    PubMed 9245983

  • Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A, Dreyfuss G, Melki J. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet. 1997 Jul;16(3):265-9. doi: 10.1038/ng0797-265.

    PubMed 9207792

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Valproic Acid in people with Spinal Muscular Atrophy, run by University of Utah at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To assess safety and tolerability of VPA in SMA patients greater than 2 years of age. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00374075, which also lists 43 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.

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