- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00528268
Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy (STOPSMA)
June 14, 2015 updated by: Kathryn Swoboda, University of Utah
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
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Utah
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Salt Lake City, Utah, United States, 84132
- University of Utah
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 day to 6 months (CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
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
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Cohort 1
Family history of SMA type I 0-3 months old Confirmation of no more than 3 SMN2 copies
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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
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Number of participants with SAE's related to research.
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24 months
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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.
Time Frame: 24 months
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24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Kathryn Swoboda, MD, University of Utah
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
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 (ESTIMATE)
September 12, 2007
Study Record Updates
Last Update Posted (ESTIMATE)
July 3, 2015
Last Update Submitted That Met QC Criteria
June 14, 2015
Last Verified
June 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Neuromuscular Manifestations
- Pathological Conditions, Anatomical
- Spinal Cord Diseases
- Motor Neuron Disease
- Muscular Atrophy
- Atrophy
- Muscular Atrophy, Spinal
- Antineoplastic Agents
- 4-phenylbutyric acid
Other Study ID Numbers
- 22183 (Other Identifier: City of Hope Medical Center)
- 1R01HD054599-01 (NIH)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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