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

This study has been completed.
Sponsor:
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00568698
First received: December 4, 2007
Last updated: July 7, 2009
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Muscular Atrophy, Spinal
Drug: Hydroxyurea
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Pilot Therapeutic Trial Using Hydroxyurea in Type I Spinal Muscular Atrophy Patients

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Safety: Frequency of Adverse Events/Lab Abnormalities
  • Efficacy: Length of survival (LOS) and age of ventilator dependence (AVD)

Secondary Outcome Measures:
  • Motor Unit Number Estimation (MUNE)
  • Biomarker Assays: SMN Protein and SMN mRNA

Estimated Enrollment: 18
Study Start Date: January 2004
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   up to 2 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00568698

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Dr Ching H. Wang Stanford University
  More Information

No publications provided

Responsible Party: Dr Ching H. Wang, Principal Investigator, Stanford University School of Medicine
ClinicalTrials.gov Identifier: NCT00568698     History of Changes
Obsolete Identifiers: NCT00083746
Other Study ID Numbers: SU-11012007-783, 78811
Study First Received: December 4, 2007
Last Updated: July 7, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Muscular Atrophies of Childhood
Central Nervous System Diseases
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Motor Neuron Disease
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Neuromuscular Diseases
Neuromuscular Manifestations
Pathological Conditions, Anatomical
Signs and Symptoms
Spinal Cord Diseases
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014