Clinical trial NCT00568802: A Pilot Therapeutic Trial Using Hydroxyurea in Type II and Type III Spinal Muscular Atrophy Patients
Official title: A Pilot Therapeutic Trial Using Hydroxyurea in Type II and Type III Spinal Muscular Atrophy Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Muscular Atrophy, Spinal
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2007-12-06
Enrollment: 27
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.

Eligibility 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 independent 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

Primary outcomes:
measure: Efficacy: Functional Motor Testing, Including Gross Motor Function Measure (GMFM) and Timed Motor Tests
timeFrame: Up to 6 years, 2 months
measure: Safety: Frequency of Adverse Events/Lab Abnormalities
timeFrame: Up to 6 years, 2 months
Secondary outcomes:
measure: Pulmonary Function Testing
timeFrame: Up to 6 years, 2 months
measure: Motor Unit Number Estimation (MUNE)
timeFrame: Up to 6 years, 2 months
measure: Biomarker Assays: SMN Protein and SMN mRNA
timeFrame: Up to 6 years, 2 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Dr Ching H. Wang
role: PRINCIPAL_INVESTIGATOR
References: