Back to resultsStudy to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy (STOPSMA)
Primary Purpose
Spinal Muscular Atrophy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sodium phenylbutyrate (NaPB)
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Muscular Atrophy focused on measuring Spinal Muscular Atrophy, SMA, Sodium Phenylbutyrate
Eligibility 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.
Sites / Locations
- University of Utah
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Family history of SMA type I 0-3 months old Confirmation of no more than 3 SMN2 copies
Family history of SMA type II 0-6 months old Confirmation of no more than 4 SMN2 copies
Outcomes
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.
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.
Full Information
NCT ID
NCT00528268
First Posted
September 10, 2007
Last Updated
June 14, 2015
Sponsor
University of Utah
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT00528268
Brief Title
Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
Acronym
STOPSMA
Official Title
Prospective Phase I/II Study to Evaluate Effects of Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Muscular Atrophy
Keywords
Spinal Muscular Atrophy, SMA, Sodium Phenylbutyrate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Family history of SMA type I 0-3 months old Confirmation of no more than 3 SMN2 copies
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Family history of SMA type II 0-6 months old Confirmation of no more than 4 SMN2 copies
Intervention Type
Drug
Intervention Name(s)
Sodium phenylbutyrate (NaPB)
Intervention Description
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 Measure Information:
Title
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.
Description
Number of participants with SAE's related to research.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathryn Swoboda, MD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
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