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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Kathryn Swoboda, University of Utah
ClinicalTrials.gov Identifier:
NCT00528268
First received: September 10, 2007
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Spinal Muscular Atrophy
Drug: Sodium phenylbutyrate (NaPB)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Utah:

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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: July 2007
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Family history of SMA type I 0-3 months old Confirmation of no more than 3 SMN2 copies
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 2
Family history of SMA type II 0-6 months old Confirmation of no more than 4 SMN2 copies
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.

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.

  Eligibility

Ages Eligible for Study:   up to 6 Months
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00528268

Locations
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Kathryn Swoboda, MD University of Utah
  More Information

No publications provided

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
Study First Received: September 10, 2007
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Utah:
Spinal Muscular Atrophy
SMA
Sodium Phenylbutyrate

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Central Nervous System Diseases
Motor Neuron Disease
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Neuromuscular Diseases
Neuromuscular Manifestations
Pathological Conditions, Anatomical
Signs and Symptoms
Spinal Cord Diseases
4-phenylbutyric acid
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014