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

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.

Study Overview

• Status: Completed
• Conditions: Spinal Muscular Atrophy
• Intervention / Treatment: Drug: Sodium phenylbutyrate

Detailed Description

Perform a phase I/II study to evaluate effects of sodium phenylbutyrate (NaPB) in a cohort of presymptomatic infants, predicted to develop either SMA type 1 or SMA type 2 given genotype and family history of an older sibling with the respective SMA type. Primary outcomes: 1) to collect additional safety and pharmacokinetic data in neonates and young infants administered NaPB 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 between cohorts and between each cohort and participants from our natural history database matched for age, SMN2 dosage and gender.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 6 months (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cohort 1; Treatment with sodium phenylbutyrate; age < 3 months; history of sibling(s) with type I SMA; SMN2 dosage < 3 copies	Drug: Sodium phenylbutyrate; Sodium phenylbutyrate is dispensed as a powder, 450-600 mg/kg/day, divided into four doses. For cohort 1, treatment and monitoring continues for 18 months. For cohort 2, treatment and monitoring continues for 24 months.; Other Names: NaPB
Active Comparator: cohort 2; Treatment with sodium phenylbutyrate; age < 6 months; history of sibling(s) with type II SMA; SMN2 dosage < 4 copies	Drug: Sodium phenylbutyrate; Sodium phenylbutyrate is dispensed as a powder, 450-600 mg/kg/day, divided into four doses. For cohort 1, treatment and monitoring continues for 18 months. For cohort 2, treatment and monitoring continues for 24 months.; Other Names: NaPB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of Sodium Phenylbutyrate in Neonates and Infants With SMA	The number of participants able to achieve specific developmental milestones, such as sitting unsupported or walking independently, during the study period.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The Study Will Determine Potential Benefit of NaPB on Lean Body Mass; Overall Motor Function; Potential Cellular Response to NaPB; and Drug Compliance.	24 months

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Kathryn Swoboda, MD, University of Utah

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: September 10, 2007
• First Submitted That Met QC Criteria: September 10, 2007
• First Posted (Estimated): September 12, 2007

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Spinal Muscular Atrophy; SMA; Sodium Phenylbutyrate
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; Motor Neuron Disease; Atrophy; Muscular Atrophy; Muscular Atrophy, Spinal; Antineoplastic Agents; 4-phenylbutyric acid
• Other Study ID Numbers: 22183 (Other Identifier: City of Hope Medical Center); 1R01HD054599-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon request, to include the following outcomes data: 1) degree of denervation as measured over time by maximum ulnar compound muscle action potential amplitude (both cohorts); % of patients who die or require > 16 hours ventilator support for more than 4 weeks by 18 months of age (cohort I); % of patients who achieve independent sitting for at least 30 seconds (cohort I); % of patient who achieve independent ambulation by 2 years of age (cohort II)