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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Muscular Atrophy, Spinal	Drug: Hydroxyurea	Phase 1; Phase 2

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 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	24 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	Double
Primary Purpose:	Treatment
Official Title:	A Pilot Therapeutic Trial Using Hydroxyurea in Type II and Type III Spinal Muscular Atrophy Patients
Study Start Date :	January 2004

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Pulmonary Function Testing
2. Motor Unit Number Estimation (MUNE)
3. Biomarker Assays: SMN Protein and SMN mRNA

Eligibility Criteria

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Ages Eligible for Study:	1 Year to 10 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:1. Laboratory confirmation of a homozygous deletion or mutation of the SMN1 gene 2. (Type II) Can sit independently but cannot walk without support by the age of 16 months and never achieve independent walking thereafter; OR (Type III) Can walk independently within the first 2 years of life, but showing rapid progression of weakness resulting in the loss of idependent ambulation by 6 years of age 3. Patient is older than 16 months and younger than 8 years old at the time of enrollment
 Exclusion Criteria:1. Known hematological disorders, other systemic disorders, or severe birth asphyxia 2. Participation in SMA clinical trials for other experimental drugs 3. Requiring continuous respiratory support before the initiation of HU treatment

Contacts and Locations

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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

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ClinicalTrials.gov Identifier:	NCT00568802 History of Changes
Obsolete Identifiers:	NCT00084006
Other Study ID Numbers:	SU-11012007-781; 79233
First Posted:	December 6, 2007
Last Update Posted:	December 3, 2008
Last Verified:	December 2008

Additional relevant MeSH terms:

Atrophy; Muscular Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Spinal Cord Diseases; Pathological Conditions, Anatomical; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Central Nervous System Diseases	Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, Inborn; Hydroxyurea; Antineoplastic Agents; Antisickling Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors