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

NCT ID: NCT00528268

Last Updated: 2025-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2013-12-31

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 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.

Conditions

Spinal Muscular Atrophy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

cohort 1

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

Group Type: ACTIVE_COMPARATOR

Sodium phenylbutyrate

Intervention Type: 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.

cohort 2

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

Group Type: ACTIVE_COMPARATOR

Sodium phenylbutyrate

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

NaPB

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kathryn Swoboda, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

1R01HD054599-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22183

Identifier Type: -

Identifier Source: org_study_id