Trial reportMultiple sclerosis and related disorders2020
Idebenone does not inhibit disability progression in primary progressive MS.
Trial report in Multiple sclerosis and related disorders, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00950248 (Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Clemastine fumarate accelerates accumulation of disability in progressive multiple sclerosis by enhancing pyroptosis.The Journal of clinical investigation · 2025Trial
- Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain.Scientific reports · 2025Article
- Biomarkers of progressive multiple sclerosis decrease following autologous hematopoietic stem cell transplantation.Journal of neuroinflammation · 2025Article
- Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort.International journal of molecular sciences · 2024Article
- Antioxidant Therapies in the Treatment of Multiple Sclerosis.Biomolecules · 2024Review
- Cysteine sulfenylation contributes to liver fibrosis via the regulation of EphB2-mediated signaling.Cell death & disease · 2024Article
- The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024Review
- Quinones as Neuroprotective Agents.Antioxidants (Basel, Switzerland) · 2023Review
- Molecular models of multiple sclerosis severity identify heterogeneity of pathogenic mechanisms.Nature communications · 2022Article
- A Narrative Review on Axonal Neuroprotection in Multiple Sclerosis.Neurology and therapy · 2022Review
- Designing Multi-arm Multistage Adaptive Trials for Neuroprotection in Progressive Multiple Sclerosis.Neurology · 2022Article
- The role of glial cells in multiple sclerosis disease progression.Nature reviews. Neurology · 2022Review
- Central nervous system macrophages in progressive multiple sclerosis: relationship to neurodegeneration and therapeutics.Journal of neuroinflammation · 2022Review
- Crosstalk between Neuron and Glial Cells in Oxidative Injury and Neuroprotection.International journal of molecular sciences · 2021Review
- Review
- Facing the urgency of therapies for progressive MS - a Progressive MS Alliance proposal.Nature reviews. Neurology · 2021Review
- Targeting for Success: Demonstrating Proof-of-Concept with Mechanistic Early Phase Clinical Pharmacology Studies for Disease-Modification in Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy.PloS one · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMultiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder of the central nervous system (CNS). While current MS therapies target the inflammatory processes, no treatment explicitly targets mitochondrial dysfunction and resulting axonal loss. Therefore, the aim of this study was to determine whether idebenone inhibits mitochondrial dysfunction and accumulation of disability in primary progressive MS (PPMS) and to enhance understanding of pathogenic mechanisms of PPMS progression using cerebrospinal fluid (CSF) biomarkers.
methodsThe double-blind, placebo-controlled Phase I/II clinical trial of Idebenone in patients with Primary Progressive MS (IPPoMS; NCT00950248) was an adaptively designed, baseline-versus-treatment, placebo-controlled, CSF-biomarker-supported trial. Based on interim analysis of the 1-year pre-treatment data, change in the area under the curve of Combinatorial Weight-Adjusted Disability Score (CombiWISE) became the primary outcome, with >80% power to detect ≥40% efficacy with 28 patients/arm treated for 2 years in baseline versus treatment paradigm. Changes in traditional disability scales and in brain ventricular volume were secondary outcomes. Exploratory outcomes included CSF biomarkers of mitochondrial dysfunction (Growth/differentiation factor 15 [GDF15] and lactate), axonal damage (neurofilament light chain [NFL]), innate immunity (sCD14), blood brain barrier leakage (albumin quotient) and retinal nerve fiber layer thinning.
resultsIdebenone was well tolerated but did not inhibit disability progression or CNS tissue destruction. Concentrations of GDF15, secreted predominantly by astrocytes and choroid plexus epithelium in vitro, increased after exposure to mitochondrial toxin rotenone, validating the ability of this biomarker to measure intrathecal mitochondrial damage. CSF GDF15 levels correlated strongly with age and MS patients had CSF levels of GDF15 significantly above age-adjusted healthy volunteers, with highest levels measured in PPMS. Idebenone did not change CSF GDF15 levels.
conclusionMitochondrial dysfunction exceeding normal aging reflected by age-adjusted CSF GDF15 is present in the majority of PPMS patients, but it is not inhibited by idebenone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.