Randomized, double-blind, placebo-controlled trial of hydroxyurea in spinal muscular atrophy
| Autor: | Y. C. Chen, S. N. Yang, Yuh-Jyh Jong, Jan-Gowth Chang, Y. C. Wu, S. M. Wu, Yi-Hsin Yang, Tai-Heng Chen, Yining Huang, H. H. Mai, Haiyan Wang, Wen-Chen Liang |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Neutropenia Adolescent Side effect Vital Capacity Placebo-controlled study Motor Activity Placebo law.invention Muscular Atrophy Spinal Young Adult FEV1/FVC ratio Double-Blind Method Randomized controlled trial law medicine Humans Hydroxyurea RNA Messenger Treatment Failure Child Nucleic Acid Synthesis Inhibitors Motor Neurons Dose-Response Relationship Drug business.industry medicine.disease SMA Surgery Clinical trial Child Preschool Anesthesia Female Neurology (clinical) business Follow-Up Studies |
| Zdroj: | Neurology. 75:2190-2197 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0b013e3182020332 |
| Popis: | Objective: The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial. Methods: Twenty-eight patients with type 2 SMA and 29 patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1–T2) and then every 2 months throughout treatment (T3–T10) and posttreatment periods (T11–T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC). Results: Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had −1.88 for GMFM (p = 0.11), −0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function. Conclusion: Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia. Classification of evidence: This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA. |
| Databáze: | OpenAIRE |
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