Clinical Trial: A Pilot Therapeutic Trial Using Hydroxyurea in Type II and Type III Spinal Muscular Atrophy Patients

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: A Pilot Therapeutic Trial Using Hydroxyurea in Type II and Type III Spinal Muscular Atrophy Patients

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

Detailed Summary:

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 II (intermediate) SMA has its onset in early childhood (prior to 18 months) and is characterized by the failure to stand or walk unassisted. Individuals with Type III SMA (mild SMA or Kugelberg-Welander disease) typically develop symptoms after 18 months of age and display a wide range of clinical heterogeneity. The clinical spectrum ranges from rapid progressive weakness resulting in wheelchair dependence in late childhood to patients being able to walk in adult years and living productive and independent lifestyles for the majority of their lives.

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 Types II and III SMA. This clinical trial study is intended to establish the safety profile in children with Types II and III SMA; to identify reliable outcome measures; and to detect the possible clinical efficacy of HU treatment in children with Types II and III SMA.


Sponsor: Stanford University

Current Primary Outcome:

  • Efficacy: Functional Motor Testing, including Gross Motor Function Measure (GMFM) and Timed Motor Tests
  • Safety: Frequency of Adverse Events/Lab Abnormalities


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Pulmonary Function Testing
  • Motor Unit Number Estimation (MUNE)
  • Biomarker Assays: SMN Protein and SMN mRNA


Original Secondary Outcome: Same as current

Information By: Stanford University

Dates:
Date Received: December 4, 2007
Date Started: January 2004
Date Completion:
Last Updated: December 2, 2008
Last Verified: December 2008