Clinical trials in amyotrophic lateral sclerosis: why so many negative trials and how can trials be improved?

  title={Clinical trials in amyotrophic lateral sclerosis: why so many negative trials and how can trials be improved?},
  author={Hiroshi Mitsumoto and Benjamin Rix Brooks and Vincenzo Silani},
  journal={The Lancet Neurology},

Advances in disease-modifying pharmacotherapies for the treatment of amyotrophic lateral sclerosis

Post-hoc analyses reveal that future clinical trials should include disease-staging procedures, longer-term trials to correctly assess survival, genetic studies of participants to aid in stratification, and more similarity between the protocols on preclinical models and clinical trials.

The clinical trial landscape in amyotrophic lateral sclerosis—Past, present, and future

This work summarizes and classify interventional therapeutic strategies based on their molecular targets and phenotypic effects in ALS and discusses possible reasons for the failure of clinical trials in ALS.

Innovating Clinical Trials for Amyotrophic Lateral Sclerosis Challenging the Established Order

A flexible design framework is proposed that naturally adapts the trial duration when inaccurate assumptions are made at the design stage, such as enrollment or survival rate, and may serve as a blueprint for future clinical trials in this population of patients.

Innovating Clinical Trials for Amyotrophic Lateral Sclerosis

A flexible design framework is proposed which naturally adapts the trial duration when inaccurate assumptions are made at the design stage such as the enrollment or survival rate and may serve a blueprint for future clinical trials in this population of patients.

A retrospective review of the progress in amyotrophic lateral sclerosis drug discovery over the last decade and a look at the latest strategies

A two-pronged approach may prove essential to achieve clinical efficacy in the identification of novel targets and preclinical testing in multiple models to identify biomarkers that can function in diagnostic, predictive and prognostic roles, and changes to clinical trial design and patient recruitment criteria are suggested.

Shortcomings in the Current Amyotrophic Lateral Sclerosis Trials and Potential Solutions for Improvement

This review has outlined the possible reasons for failure of ALS clinical trials, addressed the factors limiting timely diagnosis, and suggested possible solutions for future considerations for each of the shortcomings.

Considerations for Amyotrophic Lateral Sclerosis (ALS) Clinical Trial Design

Thoughtful clinical trial design is critical for efficient therapeutic development, particularly in the field of amyotrophic lateral sclerosis (ALS), where trials often aim to detect modest treatment

Amyotrophic Lateral Sclerosis, 2016: existing therapies and the ongoing search for neuroprotection

This article lays out the current understanding of disease genesis and physiology in relation to drug development in ALS, stressing important accomplishments and gaps in knowledge and discusses the prion-protein hypothesis of neurodegeneration.

Stem cell treatments for amyotrophic lateral sclerosis: a critical overview of early phase trials

This review covers the key advances from early phase clinical trials of stem cell therapy for ALS and identifies promising avenues and key challenges.

Clinical trials in the ALS syndrome: it is time for change

  • M. Swash
  • Medicine, Psychology
    Journal of Neurology, Neurosurgery, and Psychiatry
  • 2019
Twenty-five years have passed since the first successful trial of riluzole in amyotrophic lateral sclerosis (ALS), a study that concluded that the drug had a modest effect in extending life



Emerging drugs for amyotrophic lateral sclerosis

A review of recent discoveries relating to pathogenic mechanisms involved in disease development and progression in ALS highlights recent discoveries and their implications for the development of drug therapy.

Of mice and men: Reconciling preclinical ALS mouse studies and human clinical trials

Two separate studies provide an opportunity to reflect on how drugs for neurodegenerative disease are investigated and a new clinical trial of creatine was found to be ineffective in ALS, whereas a drug trial in an ALS mouse model finds for the first time that multiple drugs, three, additively slow down the disease.

Current pharmacological management of amyotropic lateral sclerosis and a role for rational polypharmacy

Based on the available data, it is the opinion that combination drug therapies should be considered for future clinical trials.

A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group.

The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis, and it may improve survival in patients with disease of bulbar onset, according to a prospective, double-blind, placebo-controlled trial in 155 outpatients with Amyotrophicateral sclerosis.

Can selection of rapidly progressing patients shorten clinical trials in amyotrophic lateral sclerosis?

This strategy of selecting patients with rapidly progressing ALS for inclusion in exploratory, short phase II clinical trials offers substantial savings in costs and time, and could accelerate the process of testing potentially useful drugs for the treatment of ALS.

Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis

This study provided Class IV evidence that lithium carbonate does not slow the rate of decline of function in patients with ALS over 13 months, and the lack of therapeutic benefit and safety concerns, taken together with similar results from 2 other recent trials, weighs against the use of lithium Carbonate.

Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials

  • V. MeiningerG. Bensimon W. Robberecht
  • Medicine
    Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases
  • 2004
Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS, and dose‐dependent side effects were largely associated with the serotonergic properties of the drug.