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Sponsored by: |
Kaohsiung Medical University Chung-Ho Memorial Hospital |
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Information provided by: | Kaohsiung Medical University Chung-Ho Memorial Hospital |
ClinicalTrials.gov Identifier: | NCT00485511 |
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 |
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Spinal Muscular Atrophy |
Drug: Hydroxyurea |
Phase II Phase III |
Study Type: | Interventional |
Study Design: | Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | A Randomized, Double-Blind, Placebo-Controlled Trial of Hydroxyurea in Spinal Muscular Atrophy |
Ages Eligible for Study: | 4 Years and older |
Genders Eligible for Study: | Both |
Inclusion Criteria:
Exclusion Criteria:
Contact: Yuh Jyh Jong, MD | 886-7-3121101 ext 2102 | yjjong@kmu.edu.tw |
Contact: Wen Chen Liang, MD | 886-7-3121101 ext 6507 | u9351105@kmu.edu.tw |
Taiwan | |
Kaohsiung Medical University Hospital | Recruiting |
Kaohsiung, Taiwan, 807 | |
Contact: Yuh Jyh Jong, MD 886-7-3121101 ext 2102 yjjong@kmu.edu.tw |
Principal Investigator: | Yuh Jyh Jong, MD | Vice President, Kaohsiung Medical University |
Study ID Numbers: | DOH96-TD-I-111-TM103 |
Study First Received: | June 11, 2007 |
Last Updated: | February 28, 2008 |
ClinicalTrials.gov Identifier: | NCT00485511 |
Health Authority: | Taiwan: Department of Health |
Pathological Conditions, Anatomical Spinal Cord Diseases Hydroxyurea Spinal muscular atrophy Central Nervous System Diseases Degenerative motor system disease Neurodegenerative Diseases Motor neuron disease |
Progressive spinal muscular atrophy Signs and Symptoms Neuromuscular Diseases Muscular Atrophy, Spinal Neurologic Manifestations Atrophy Motor Neuron Disease Muscular Atrophy |
Neuromuscular Manifestations Antisickling Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Therapeutic Uses |
Hematologic Agents Nervous System Diseases Enzyme Inhibitors Nucleic Acid Synthesis Inhibitors Pharmacologic Actions |