A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy

Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber’s hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young ad...

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Main Authors:	Klopstock, Thomas, Yu-Wai-Man, Patrick, Dimitriadis, Konstantinos, Rouleau, Jacinthe, Heck, Suzette, Bailie, Maura, Atawan, Alaa, Chattopadhyay, Sandip, Schubert, Marion, Garip, Aylin, Kernt, Marcus, Petraki, Diana, Rummey, Christian, Leinonen, Mika, Metz, Günther, Griffiths, Philip G., Meier, Thomas, Chinnery, Patrick F.
Format:	Online
Language:	English
Published:	Oxford University Press 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170530/

id	pubmed-3170530
recordtype	oai_dc
spelling	pubmed-31705302011-09-12 A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy Klopstock, Thomas Yu-Wai-Man, Patrick Dimitriadis, Konstantinos Rouleau, Jacinthe Heck, Suzette Bailie, Maura Atawan, Alaa Chattopadhyay, Sandip Schubert, Marion Garip, Aylin Kernt, Marcus Petraki, Diana Rummey, Christian Leinonen, Mika Metz, Günther Griffiths, Philip G. Meier, Thomas Chinnery, Patrick F. Original Articles Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber’s hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber’s hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber’s hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber’s hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated. Oxford University Press 2011-09 2011-07-23 /pmc/articles/PMC3170530/ /pubmed/21788663 http://dx.doi.org/10.1093/brain/awr170 Text en © The Author (2011). Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Klopstock, Thomas Yu-Wai-Man, Patrick Dimitriadis, Konstantinos Rouleau, Jacinthe Heck, Suzette Bailie, Maura Atawan, Alaa Chattopadhyay, Sandip Schubert, Marion Garip, Aylin Kernt, Marcus Petraki, Diana Rummey, Christian Leinonen, Mika Metz, Günther Griffiths, Philip G. Meier, Thomas Chinnery, Patrick F.
spellingShingle	Klopstock, Thomas Yu-Wai-Man, Patrick Dimitriadis, Konstantinos Rouleau, Jacinthe Heck, Suzette Bailie, Maura Atawan, Alaa Chattopadhyay, Sandip Schubert, Marion Garip, Aylin Kernt, Marcus Petraki, Diana Rummey, Christian Leinonen, Mika Metz, Günther Griffiths, Philip G. Meier, Thomas Chinnery, Patrick F. A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy
author_facet	Klopstock, Thomas Yu-Wai-Man, Patrick Dimitriadis, Konstantinos Rouleau, Jacinthe Heck, Suzette Bailie, Maura Atawan, Alaa Chattopadhyay, Sandip Schubert, Marion Garip, Aylin Kernt, Marcus Petraki, Diana Rummey, Christian Leinonen, Mika Metz, Günther Griffiths, Philip G. Meier, Thomas Chinnery, Patrick F.
author_sort	Klopstock, Thomas
title	A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy
title_short	A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy
title_full	A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy
title_fullStr	A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy
title_full_unstemmed	A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy
title_sort	randomized placebo-controlled trial of idebenone in leber’s hereditary optic neuropathy
description	Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber’s hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber’s hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber’s hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber’s hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.
publisher	Oxford University Press
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170530/
_version_	1611474850455486464

A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy

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