Muscular Atrophy, Spinal
Conditions
Brief 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.
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.
Interventions
DRUGHydroxyurea
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
No minimum to 2 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Frequency of Adverse Events/Lab Abnormalities | Up to 8 years, 1 month |
| Efficacy: Length of Survival (LOS) and Age of Ventilator Dependence (AVD) | Up to 8 years, 1 month |
Secondary
| Measure | Time frame |
|---|---|
| Biomarker Assays: SMN Protein and SMN mRNA | Up to 8 years, 1 month |
| Motor Unit Number Estimation (MUNE) | Up to 8 years, 1 month |
Countries
United States
Participant flow
Pre-assignment details
Data are presented for all participants because data relating to arm assignment are no longer accessible; the Principal Investigator (PI) has left institution and all efforts to locate the data have been exhausted.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants received hydroxyurea, or placebo to match hydroxyurea. | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 29 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Efficacy: Length of Survival (LOS) and Age of Ventilator Dependence (AVD)
Time frame: Up to 8 years, 1 month
Population: Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.
Primary
Safety: Frequency of Adverse Events/Lab Abnormalities
Time frame: Up to 8 years, 1 month
Population: Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.
Secondary
Biomarker Assays: SMN Protein and SMN mRNA
Time frame: Up to 8 years, 1 month
Population: Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.
Secondary
Motor Unit Number Estimation (MUNE)
Time frame: Up to 8 years, 1 month
Population: Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.