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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Kathryn Swoboda, University of Utah
ClinicalTrials.gov Identifier:
NCT00528268
First received: September 10, 2007
Last updated: April 22, 2013
Last verified: April 2013

September 10, 2007
April 22, 2013
July 2007
December 2013   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
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 ]
Complete list of historical versions of study NCT00528268 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: No ]
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 ]
Not Provided
Not Provided
 
Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
Prospective Phase I/II Study to Evaluate Effects of Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Spinal Muscular Atrophy
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.
  • 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)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
12
December 2013
December 2013   (final data collection date for primary outcome measure)

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.
Both
up to 6 Months
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00528268
22183, 1R01HD054599-01
Yes
Kathryn Swoboda, University of Utah
University of Utah
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Kathryn Swoboda, MD University of Utah
University of Utah
April 2013

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