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A Trial of Hydroxyurea in Spinal Muscular Atrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00485511
Recruitment Status : Completed
First Posted : June 13, 2007
Last Update Posted : February 15, 2010
Information provided by:
Kaohsiung Medical University Chung-Ho Memorial Hospital

Brief Summary:

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 or disease Intervention/treatment Phase
Spinal Muscular Atrophy Drug: Hydroxyurea Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial of Hydroxyurea in Spinal Muscular Atrophy
Study Start Date : June 2007
Actual Primary Completion Date : June 2009
Actual Study Completion Date : June 2009

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00485511

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

Layout table for additonal information Identifier: NCT00485511     History of Changes
Other Study ID Numbers: DOH96-TD-I-111-TM103
First Posted: June 13, 2007    Key Record Dates
Last Update Posted: February 15, 2010
Last Verified: February 2010
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
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