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

NCT00528268 | Completed Phase 1 Results DMC

• 2 other identifiers: 221831R01HD054599-01
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Muscular Atrophy

Keywords

Spinal Muscular Atrophy; SMA; Sodium Phenylbutyrate

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

cohort 1

ACTIVE COMPARATOR

Treatment with sodium phenylbutyrate; age \< 3 months; history of sibling(s) with type I SMA; SMN2 dosage \< 3 copies

Drug: Sodium phenylbutyrate

cohort 2

ACTIVE COMPARATOR

Treatment with sodium phenylbutyrate; age \< 6 months; history of sibling(s) with type II SMA; SMN2 dosage \< 4 copies

Drug: Sodium phenylbutyrate

Interventions

Sodium phenylbutyrate DRUG

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.

Also known as: NaPB

cohort 1; cohort 2

Eligibility Criteria

• Age: 1 Day - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

4-phenylbutyric acid

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Dr. Kathryn Swoboda
• Organization: University of Utah

swoboda@genetics.utah.edu

801-585-9717

Study Officials

• Kathryn Swoboda, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2007
• First Posted: September 12, 2007
• Study Start: July 1, 2007
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 28, 2025
• Results First Posted: July 3, 2015

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)