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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2296-2301. Prepublished online as a Blood First Edition Paper on July 3, 2007; DOI 10.1182/blood-2007-02-075960. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-02-075960v1 110/7/2296    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Elstein, D. Articles by Zimran, A. Search for Related Content PubMed PubMed Citation Articles by Elstein, D. Articles by Zimran, A. Related Collections Clinical Trials and Observations Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement Deborah Elstein1, Altoon Dweck1, Drorit Attias1, Irith Hadas-Halpern1, Shoshana Zevin1, Gheona Altarescu1, Johannes F. M. G. Aerts2, Sonja van Weely2, and Ari Zimran1 1 Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; 2 Department of Biochemistry, Academic Medical Center, Amsterdam, the Netherlands Enzyme replacement therapy (ERT) with imiglucerase reduces hepatosplenomegaly and improves hematologic parameters in Gaucher disease type 1 within 6-24 months. Miglustat reduces organomegaly, improves hematologic parameters, and reverses bone marrow infiltration. This trial evaluates miglustat in patients clinically stable on ERT. Tolerability of miglustat and imiglucerase, alone and in combination, pharmacokinetic profile, organ reduction, and chitotriosidase activity were assessed. Thirty-six patients stable on imiglucerase were randomized into this phase II, open-label trial. Statistically significant changes from baseline were assessed (paired t test) on primary objectives with secondary analyses on biochemical and safety parameters. Liver and spleen volume were unchanged in switched patients. No significant differences were seen between groups regarding mean change in hemoglobin. Mean change in platelet counts was only significant between miglustat and imiglucerase groups (P = .035). Chitotriosidase activity remained stable. In trial extension, clinical endpoints were generally maintained. Miglustat was well tolerated alone or in combination. Miglustat's safety profile was consistent with previous trials; moreover, no new cases of peripheral neuropathy were observed. Gaucher disease type 1 (GD1) parameters were stable in most switched patients. Combination therapy did not show benefit. Findings suggest miglustat could be an effective maintenance therapy in stabilized patients with GD1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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