Phase III randomized trial of  gabapentin in patients with  amyotrophic lateral sclerosis

Miller, Robert G.; Moore, Dan H.; Gelinas, Deborah; Dronsky, V.; Mendoza, Michelle C.; Barohn, Richard J.; Bryan, Wilson W.; Ravits, John; Yuen, Eric; Neville, Hans E.; Ringel, Steven P.; Bromberg, Mark B.; Petajan, Jack H.; Amato, Antonio; Jackson, Carlayne E.; Johnson, William W.; Mandler, Raúl N.; Bosch, Pere Ventayol; Smith, Bradley N.; Graves, Michael C.; Ross, Mark A.; Sorenson, Eric J.; Kelkar, Praful; Parry, Gareth; Olney, Richard K.

doi:10.1212/wnl.56.7.843

Cited by 189 publications

(96 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The isometric strength aspect of this work was further improved by the creation of a "megascore," or a z-averaged score across a predefined set of muscles [25]. Such maximal isometric voluntary contraction was incorporated into a variety of trials in the 1990s and early 2000s [9,[26][27][28]. While providing good data, the methodology was very challenging to institute, as it required a large plinth upon which the debilitated patient needed to be placed; this became especially challenging as patients became too weak to transfer.…”

Section: Strength Measurements Including Handheld Dynamometry Maximmentioning

confidence: 99%

Clinical Measures of Disease Progression in Amyotrophic Lateral Sclerosis

Rutkove

2015

Neurotherapeutics

View full text Add to dashboard Cite

Progressive weakness remains the clinical hallmark of amyotrophic lateral sclerosis (ALS). Accordingly, a variety of tools has been developed to capture this disease feature, including questionnaires, such as the ALS-functional rating scale, strength testing, pulmonary function tests, electrophysiologic measures, including motor unit number estimation, and imaging techniques. Despite this plethora of approaches, there is little agreement as to what measures to use in a given clinical trial or in the clinic during routine patient care. Part of the reason for this uncertainty is that ALS is a remarkably protean disease. Some individuals progress rapidly, others slowly; some patients have considerable upper motor neuron dysfunction, whereas others have little; and there is considerable variation in the sequence of body regions affected, in some the disease beginning in the bulbar musculature and in others in one arm or one leg. Here, I present a variety of basic and more complex clinical measures for potential use in therapeutic trials with the aim of offering a balanced and practical set of recommendations, as well as considerations for future studies.

show abstract

Section: Strength Measurements Including Handheld Dynamometry Maximmentioning

confidence: 99%

Clinical Measures of Disease Progression in Amyotrophic Lateral Sclerosis

Rutkove

2015

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

“…For example, in two trials gabapentin increased the rate of disease progression in patients with ALS 55 . A similar effect was reported in patients with ALS who received the GABAergic compound topiramate 56 .…”

Section: Modulating Inhibitory Activity Can Explain the Progression Omentioning

confidence: 99%

Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

Tuk

2016

F1000Res

View full text Add to dashboard Cite

Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity.

show abstract

“…Unfortunately, riluzole only extends lifespan in ALS patients by an average of 3 months so efforts have focused on identifying other compounds which can counteract glutamate excitotoxicity. A variety of other drugs targeting glutamatergic pathways (talampanel, memantine, topiramate, lamotrigine, gabapentin, ONO-2506) have been evaluated in ALS patients, but the results have not suggested a benefit on disease course (Cudkowicz et al, 2003;de Carvalho et al, 2010;Miller et al, 2001;Ryberg et al, 2003;Zinman & Cudkowicz, 2011).…”

Section: Therapeutic Agents To Target Astrocytes and Microgliamentioning

confidence: 99%