Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy (STOPSMA)
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| ClinicalTrials.gov Identifier: NCT00528268 |
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Recruitment Status :
Completed
First Posted : September 12, 2007
Results First Posted : July 3, 2015
Last Update Posted : July 3, 2015
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Sponsor:
University of Utah
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Kathryn Swoboda, University of Utah
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Brief Summary:
In this single-center trial, we will evaluate the effects of NaPB on presymptomatic Spinal Muscular Atrophy (SMA) type I (cohort 1)and presymptomatic SMA type II (cohort 2) infants. A variety of outcome measures will be performed at each study visit to follow the course of the disease. Total duration of the study for type I infants will be 18 months, for type II infants, 24 months.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Spinal Muscular Atrophy | Drug: Sodium phenylbutyrate (NaPB) | Phase 1 Phase 2 |
Perform a phase I/II study to evaluate effects of Phenyl Butyrate (PBA) in a cohort of 12 presymptomatic infants. These infants are predicted to have either SMA 1 or 2 given genotype and family history of an older sibling with the respective SMA type. Our goal is twofold: 1) to collect additional safety and pharmacokinetic data in neonates and young infants administered this compound, within the dosing guidelines already in use for urea cycle disorder therapy, and 2) to determine possible benefit of early treatment intervention with regard to status of denervation and functional motor status at specific time points for which we have matched natural history data to perform a comparison. Data obtained from this aim will guide future trials designed to determine the efficacy of PBA or other butyrate analogs in attenuating disease progression in SMA subjects identified in the presymptomatic period.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 14 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Prospective Phase I/II Study to Evaluate Effects of Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy |
| Study Start Date : | July 2007 |
| Actual Primary Completion Date : | December 2013 |
| Actual Study Completion Date : | December 2013 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Spinal muscular atrophy
MedlinePlus related topics:
Spinal Muscular Atrophy
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort 1
Family history of SMA type I 0-3 months old Confirmation of no more than 3 SMN2 copies
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Drug: Sodium phenylbutyrate (NaPB)
The powder form of the drug will be dispensed. The target NaPB dosing is 450-600 mg/kg/day, divided into four doses. For cohort 1, we propose to continue treatment for 18 months. For cohort 2, we propose to continue treatment for 24 months. |
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Experimental: Cohort 2
Family history of SMA type II 0-6 months old Confirmation of no more than 4 SMN2 copies
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Drug: Sodium phenylbutyrate (NaPB)
The powder form of the drug will be dispensed. The target NaPB dosing is 450-600 mg/kg/day, divided into four doses. For cohort 1, we propose to continue treatment for 18 months. For cohort 2, we propose to continue treatment for 24 months. |
Primary Outcome Measures :
- The Study Will Assess the Safety, Tolerability and Potential Efficacy of Sodium Phenylbutyrate (NaPB) in Presymptomatic Infants Genetically Confirmed to Have SMA. It Will Also Determine Selected Pharmacokinetic Parameters. [ Time Frame: 24 months ]Number of participants with SAE's related to research.
Secondary Outcome Measures :
- The Study Will Determine Potential Benefit of NaPB on Lean Body Mass; Overall Motor Function; Potential Cellular Response to NaPB; and Drug Compliance. [ Time Frame: 24 months ]
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| Ages Eligible for Study: | up to 6 Months (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Laboratory documentation of homozygous absence of SMN1 exon 7.
- Confirmation of no more than 3 SMN2 copies for cohort 1; no more than 4 copies for cohort 2.
- Family history of affected sibling with SMA type I for cohort 1 and SMA type II for cohort 2.
- Age ≤ 3 months, cohort 1; Age ≤ 6 months, cohort 2.
- Written informed consent of parents/guardian.
- Laboratory results demonstrating normal values for age.
Exclusion Criteria:
-Evidence of hepatic insufficiency, renal insufficiency, edema with sodium retention, known seizure disorder, urea cycle disorder, cardiac arrhythmia, congenital heart defect, hypertension, significant central nervous system (CNS) impairment, or neurodegenerative or neuromuscular disease other than SMA.
History of allergy/sensitivity to sodium phenylbutyrate (NaPB).
- Use of NaPB within 30 days of study entry.
- Serious illness requiring hospitalization ≤ 14 days prior to study entry.
- Use of medications intended for the treatment of SMA including riluzole, valproic acid, hydroxyurea, oral use of albuterol, NaPB, butyrate derivatives, creatine, growth hormone, anabolic steroids, probenecid, oral or parenteral use of corticosteroids at entry, or agents anticipated to increase or decrease muscle strength or agents with presumed histone deacetylase (HDAC) inhibition within 30 days prior to study entry.
- Unwillingness to travel for study assessments.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00528268
Locations
| United States, Utah | |
| University of Utah | |
| Salt Lake City, Utah, United States, 84132 | |
Sponsors and Collaborators
University of Utah
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
| Principal Investigator: | Kathryn Swoboda, MD | University of Utah |
| Responsible Party: | Kathryn Swoboda, Associate Professor, Neurology and Pediatrics, University of Utah |
| ClinicalTrials.gov Identifier: | NCT00528268 History of Changes |
| Other Study ID Numbers: |
22183 1R01HD054599-01 ( U.S. NIH Grant/Contract ) |
| First Posted: | September 12, 2007 Key Record Dates |
| Results First Posted: | July 3, 2015 |
| Last Update Posted: | July 3, 2015 |
| Last Verified: | June 2015 |
Keywords provided by Kathryn Swoboda, University of Utah:
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Spinal Muscular Atrophy SMA Sodium Phenylbutyrate |
Additional relevant MeSH terms:
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Atrophy Muscular Atrophy Muscular Atrophy, Spinal Spinal Cord Diseases Pathological Conditions, Anatomical Neuromuscular Manifestations Neurologic Manifestations Nervous System Diseases |
Signs and Symptoms Central Nervous System Diseases Motor Neuron Disease Neurodegenerative Diseases Neuromuscular Diseases 4-phenylbutyric acid Antineoplastic Agents |