A Pilot Therapeutic Trial Using Hydroxyurea in Type I Spinal Muscular Atrophy Patients

Phase 1

Completed

• Conditions: Muscular Atrophy, Spinal
• Interventions: Drug: Placebo to match hydroxyurea; Drug: Hydroxyurea

• Registration Number: NCT00568698
• Lead Sponsor: Stanford University

Brief Summary

The objectives of this trial are: to establish a safety profile for use of Hydroxyurea in children with Type I Spinal Muscular Atrophy; to identify reliable outcome measures for HU treatment in Type I SMA; and to detect the clinical efficacy of HU treatment in children with Type I SMA.

Detailed Description

SMA is a neuromuscular disorder characterized by degeneration of spinal cord motor neurons and muscular atrophy. SMA is classified into three clinical subtypes according to the severity and age of onset (Types I, II and III). Type I SMA (also called severe, infantile or acute SMA, or Werdnig-Hoffman disease) is the most severe phenotype. The onset of symptoms is within the first 6 months of life, and weakness of intercostal muscles and lack of airway protection lead to respiratory insufficiency and aspiration pneumonia, often resulting in early infant death.

In our laboratory, our preliminary results indicate that HU treatment significantly increases both SMN mRNA expression and intact SMN protein levels in vitro. These data confirm previous observations that in vitro treatments of SMA lymphocytes with hydroxyurea resulted in augmentation of the SMN2 gene expression in a dose and time related manner. Based on these exciting pre-clinical data, coupled with the well-documented side-effect profile of HU in children, we are conducting a pilot clinical trial using HU in children with Type I SMA. This clinical trial study is intended to establish the safety profile in children with Type I SMA; to identify reliable outcome measures; and to detect the possible clinical efficacy of HU treatment in children with Type I SMA.

Study Timeline

• Study Start: 2004-01
• Study First Submitted: 2007-12-04
• Study First Submitted QC: 2007-12-04
• Study First Posted: 2007-12-06
• Primary Completion: 2012-02
• Study Completion: 2012-02
• Status Verified: 2019-09
• Results First Submitted: 2019-09-06
• Results First Submitted QC: 2019-09-11
• Last Update Submitted: 2019-09-11
• Results First Posted: 2019-10-02
• Last Update Posted: 2019-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. Laboratory confirmation of a homozygous deletion or mutation of the SMN1 gene 2. Clinical Diagnosis of Type I SMA (never achieved independent sitting) 3. Onset of disease before the age of 6 months 4. Enrollment in study within 6 months of diagnosis

Exclusion Criteria

1. Known hematological disorders, such as chronic anemia (defined as platelet count less than 100,000/mm^3) in two contiguous measures in two weeks 2. Severe systemic disorders such as congenital heart disease, other major birth defects involving internal organs, or severe birth asphyxia 3. Participation in SMA clinical trials for other experimental drugs 4. Requiring continuous respiratory support before the initiation of HU treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo to match hydroxyurea	-
Hydroxyurea	Hydroxyurea	-

Primary Outcome Measures

Name	Time	Method
Safety: Frequency of Adverse Events/Lab Abnormalities	Up to 8 years, 1 month
Efficacy: Length of Survival (LOS) and Age of Ventilator Dependence (AVD)	Up to 8 years, 1 month

Secondary Outcome Measures

Name	Time	Method
Biomarker Assays: SMN Protein and SMN mRNA	Up to 8 years, 1 month
Motor Unit Number Estimation (MUNE)	Up to 8 years, 1 month

Trial Locations

Locations (1)

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States