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Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy (STOPSMA)

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ClinicalTrials.gov Identifier: NCT00528268
Recruitment Status : Completed
First Posted : September 12, 2007
Results First Posted : July 3, 2015
Last Update Posted : July 3, 2015
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Kathryn Swoboda, University of Utah

Tracking Information
First Submitted Date  ICMJE September 10, 2007
First Posted Date  ICMJE September 12, 2007
Results First Submitted Date  ICMJE June 14, 2015
Results First Posted Date  ICMJE July 3, 2015
Last Update Posted Date July 3, 2015
Study Start Date  ICMJE July 2007
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2015)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2007)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2007)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
Official Title  ICMJE Prospective Phase I/II Study to Evaluate Effects of Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
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.
Detailed Description 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Spinal Muscular Atrophy
Intervention  ICMJE 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.
Study Arms  ICMJE
  • Experimental: Cohort 1
    Family history of SMA type I 0-3 months old Confirmation of no more than 3 SMN2 copies
    Intervention: Drug: Sodium phenylbutyrate (NaPB)
  • Experimental: Cohort 2
    Family history of SMA type II 0-6 months old Confirmation of no more than 4 SMN2 copies
    Intervention: Drug: Sodium phenylbutyrate (NaPB)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 19, 2014)
14
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2007)
12
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 6 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00528268
Other Study ID Numbers  ICMJE 22183
1R01HD054599-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kathryn Swoboda, University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: Kathryn Swoboda, MD University of Utah
PRS Account University of Utah
Verification Date June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP