Randomized, controlled trial of miglustat in Gaucher's disease type 3

Raphael Schiffmann, Edmond J. Fitzgibbon, Chris Harris, Catherine DeVile, Elin H. Davies, Larry Abel, Ivo N. Van Schaik, William Benko, Margaret Timmons, Markus Ries, Ashok Vellodi

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Objective: To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3). Methods: This 24-month, phase II, open-label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or "no miglustat treatment." The randomized phase was followed by an optional 12-month extension phase in which all patients received miglustat. All patients received ERT during the 24-month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations. Results: Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to "no miglustat treatment." Twenty-eight patients entered the 12-month extension phase. No significant between-group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone. Interpretation: Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustat may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3.

Original languageEnglish (US)
Pages (from-to)514-522
Number of pages9
JournalAnnals of Neurology
Volume64
Issue number5
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

Fingerprint

Gaucher Disease
Randomized Controlled Trials
Enzyme Replacement Therapy
Organ Size
Saccades
miglustat
Safety
Respiratory Function Tests
Neurologic Manifestations
Lung Diseases
Therapeutics
Spleen
Clinical Trials

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Schiffmann, R., Fitzgibbon, E. J., Harris, C., DeVile, C., Davies, E. H., Abel, L., ... Vellodi, A. (2008). Randomized, controlled trial of miglustat in Gaucher's disease type 3. Annals of Neurology, 64(5), 514-522. https://doi.org/10.1002/ana.21491

Randomized, controlled trial of miglustat in Gaucher's disease type 3. / Schiffmann, Raphael; Fitzgibbon, Edmond J.; Harris, Chris; DeVile, Catherine; Davies, Elin H.; Abel, Larry; Van Schaik, Ivo N.; Benko, William; Timmons, Margaret; Ries, Markus; Vellodi, Ashok.

In: Annals of Neurology, Vol. 64, No. 5, 01.11.2008, p. 514-522.

Research output: Contribution to journalArticle

Schiffmann, R, Fitzgibbon, EJ, Harris, C, DeVile, C, Davies, EH, Abel, L, Van Schaik, IN, Benko, W, Timmons, M, Ries, M & Vellodi, A 2008, 'Randomized, controlled trial of miglustat in Gaucher's disease type 3', Annals of Neurology, vol. 64, no. 5, pp. 514-522. https://doi.org/10.1002/ana.21491
Schiffmann R, Fitzgibbon EJ, Harris C, DeVile C, Davies EH, Abel L et al. Randomized, controlled trial of miglustat in Gaucher's disease type 3. Annals of Neurology. 2008 Nov 1;64(5):514-522. https://doi.org/10.1002/ana.21491
Schiffmann, Raphael ; Fitzgibbon, Edmond J. ; Harris, Chris ; DeVile, Catherine ; Davies, Elin H. ; Abel, Larry ; Van Schaik, Ivo N. ; Benko, William ; Timmons, Margaret ; Ries, Markus ; Vellodi, Ashok. / Randomized, controlled trial of miglustat in Gaucher's disease type 3. In: Annals of Neurology. 2008 ; Vol. 64, No. 5. pp. 514-522.
@article{197ae21db2364197bf68f183616a3542,
title = "Randomized, controlled trial of miglustat in Gaucher's disease type 3",
abstract = "Objective: To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3). Methods: This 24-month, phase II, open-label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or {"}no miglustat treatment.{"} The randomized phase was followed by an optional 12-month extension phase in which all patients received miglustat. All patients received ERT during the 24-month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations. Results: Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to {"}no miglustat treatment.{"} Twenty-eight patients entered the 12-month extension phase. No significant between-group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone. Interpretation: Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustat may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3.",
author = "Raphael Schiffmann and Fitzgibbon, {Edmond J.} and Chris Harris and Catherine DeVile and Davies, {Elin H.} and Larry Abel and {Van Schaik}, {Ivo N.} and William Benko and Margaret Timmons and Markus Ries and Ashok Vellodi",
year = "2008",
month = "11",
day = "1",
doi = "10.1002/ana.21491",
language = "English (US)",
volume = "64",
pages = "514--522",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Randomized, controlled trial of miglustat in Gaucher's disease type 3

AU - Schiffmann, Raphael

AU - Fitzgibbon, Edmond J.

AU - Harris, Chris

AU - DeVile, Catherine

AU - Davies, Elin H.

AU - Abel, Larry

AU - Van Schaik, Ivo N.

AU - Benko, William

AU - Timmons, Margaret

AU - Ries, Markus

AU - Vellodi, Ashok

PY - 2008/11/1

Y1 - 2008/11/1

N2 - Objective: To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3). Methods: This 24-month, phase II, open-label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or "no miglustat treatment." The randomized phase was followed by an optional 12-month extension phase in which all patients received miglustat. All patients received ERT during the 24-month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations. Results: Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to "no miglustat treatment." Twenty-eight patients entered the 12-month extension phase. No significant between-group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone. Interpretation: Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustat may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3.

AB - Objective: To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3). Methods: This 24-month, phase II, open-label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or "no miglustat treatment." The randomized phase was followed by an optional 12-month extension phase in which all patients received miglustat. All patients received ERT during the 24-month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations. Results: Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to "no miglustat treatment." Twenty-eight patients entered the 12-month extension phase. No significant between-group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone. Interpretation: Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustat may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3.

UR - http://www.scopus.com/inward/record.url?scp=57749100376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57749100376&partnerID=8YFLogxK

U2 - 10.1002/ana.21491

DO - 10.1002/ana.21491

M3 - Article

C2 - 19067373

AN - SCOPUS:57749100376

VL - 64

SP - 514

EP - 522

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 5

ER -