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

Muscular Atrophy, Spinal Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00568698
• Other study ID #: SU-11012007-783
• Secondary ID: 78811
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2004
• Est. completion date: February 2012

Study information

• Verified date: September 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00083746

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal

Intervention

Drug:
• Hydroxyurea

• Placebo to match hydroxyurea

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Frequency of Adverse Events/Lab Abnormalities		Up to 8 years, 1 month
Primary	Efficacy: Length of Survival (LOS) and Age of Ventilator Dependence (AVD)		Up to 8 years, 1 month
Secondary	Motor Unit Number Estimation (MUNE)		Up to 8 years, 1 month
Secondary	Biomarker Assays: SMN Protein and SMN mRNA		Up to 8 years, 1 month