Clinical trial NCT00528268: Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
Official title: Prospective Phase I/II Study to Evaluate Effects of Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Spinal Muscular Atrophy
Keywords: Spinal Muscular Atrophy
SMA
Sodium Phenylbutyrate
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2007-09-12
Enrollment: 22
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety and Tolerability of Sodium Phenylbutyrate in Neonates and Infants With SMA
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Kathryn Swoboda, MD
role: PRINCIPAL_INVESTIGATOR
References: