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A Trial of Hydroxyurea in Spinal Muscular Atrophy

This study has been completed.
Information provided by:
Kaohsiung Medical University Chung-Ho Memorial Hospital Identifier:
First received: June 11, 2007
Last updated: February 11, 2010
Last verified: February 2010

Spinal muscular atrophy (SMA) is an autosomal recessive disorder in humans which results in the loss of motor neurons. It is caused by reduced levels of the survival motor neuron (SMN) protein as a result of loss or mutation of the SMN1 gene. SMN protein is encoded by two genes, SMN1 and SMN2, which essentially differ by an single nucleotide in exon 7. As a result, the majority of the transcript from SMN2 lacks exon 7. According to clinical severity, SMA was classified to three types, including type I, type II, and type III.

Drugs capable of modifying the transcription pattern of SMN2 to increase the full-length of SMN mRNA expression and the amount of SMN protein may have therapeutic effects for SMA patients. In order to test this hypothesis, we used EBV-transformed lymphoblastoid cell lines derived from the different types of SMA patients to screen the effect of various drugs on SMN2 gene expression. Hydroxyurea (HU) was found to be effective among the drugs we tested. HU is an effective therapeutic agent for patients with thalassemia and sickle cell disease which the toxicity is minimal and is well-tolerated and safely used in children. We had undergone a small-scaled 33 SMA patients randomized pilot trial (HU treatment for 8 weeks and then follow up drug-free 8 weeks) to evaluate the effect of HU in SMA patients and we got a promising preliminary data. We found that HU could significantly increase in the manual muscle testing scores at 4 weeks, and full-length SMN mRNA level in the 30mg/kg/day subgroup at 8 weeks relative to baseline, and it is safe under the dose 30mg/kg/day.

In this study, we plan to enroll 60 type II and III SMA patients and conduct a single-center, randomized, double-blind, placebo-controlled, prospective trial of two-year duration to evaluate the efficacy and safety of HU.The primary end points are the changes in full-length SMN expression, SMN protein, motor function and lung function in SMA patients. We also design a safety monitoring system to investigate the adverse effects and to assure the patients' safety. We hope we can find and prove the efficacy and safety of HU in SMA patients and set up a evaluating model for multi-center trials in the future.

Condition Intervention Phase
Spinal Muscular Atrophy Drug: Hydroxyurea Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial of Hydroxyurea in Spinal Muscular Atrophy

Resource links provided by NLM:

Further study details as provided by Kaohsiung Medical University Chung-Ho Memorial Hospital:

Study Start Date: June 2007
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)

Ages Eligible for Study:   4 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All

Inclusion Criteria:

  • Sixty SMA patients fulfilled the diagnostic criteria of SMA as defined by the International SMA Consortium (Munsat, 1992), and all had homozygous deletion of SMN1 gene but carried SMN2 gene (Chang, 1995; 1997)
  • The subjects shall each have the age older than 4 years.
  • The subjects (if age > 20 years old) or their parents (if subject age < 20 years old) shall agree with the trial and have signed the informed consents.

Exclusion Criteria:

  • The subjects shall not have hematological diseases, other severe systemic diseases and congenital anomalies except for SMA.
  • The subjects shall not have severe perinatal asphyxia history.
  • The subjects shall not be with respiratory assists.
  • The subjects shall have normal hepatic and renal functions in the pre-trial examination.
  • The subjects shall not have received operation with generalized anesthesia in past half a year.
  • The subjects shall not have acceded to other clinical trials in past half a year.
  • The subjects shall not get in this trial if they could not complete the course.
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Please refer to this study by its identifier: NCT00485511

Kaohsiung Medical University Hospital
Kaohsiung, Taiwan, 807
Sponsors and Collaborators
Kaohsiung Medical University Chung-Ho Memorial Hospital
Principal Investigator: Yuh Jyh Jong, MD Vice President, Kaohsiung Medical University
  More Information

Publications: Identifier: NCT00485511     History of Changes
Other Study ID Numbers: DOH96-TD-I-111-TM103
Study First Received: June 11, 2007
Last Updated: February 11, 2010

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
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
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors processed this record on September 21, 2017