ibudilast and Disease Exacerbation studies

Research Excerpts

Excerpt	Relevance	Reference
"Ibudilast is a nonselective phosphodiesterase inhibitor which works by blocking the cleavage of cyclic adenosine monophosphate (cAMP)."	6.53	Ibudilast for the treatment of multiple sclerosis. ( Goodman, AD; Gyang, T; Smith, AD, 2016)
"In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression."	5.27	Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis. ( Alvarez, E; Apperson, M; Ashokkumar, A; Barnes, J; Bashir, K; Bermel, RA; Coffey, CS; Cohen, BA; Conwit, R; Coyle, PK; Cudkowicz, ME; Debbins, JP; Delgado, S; Dewitt, LD; Ecklund, D; Flores, A; Fox, RJ; Giesser, BS; Gleason, T; Goldman, MD; Goodman, A; Huang, X; Jagodnik, P; Jubelt, B; Klawiter, EC; Klingner, E; Koepp, M; Krieger, S; Lava, N; Long, JD; Lowe, MJ; Lynch, SG; Matsuda, K; McGovern, M; Moses, H; Naismith, RT; Nakamura, K; Narayanan, S; Natarajan, S; Ontaneda, D; Perumal, JS; Racke, M; Repovic, P; Riley, CS; Sakaie, KE; Severson, C; Shinnar, S; Suski, V; Thoomukuntla, B; Thornell, B; Weinstock-Guttman, B; Yadav, V; Yankey, J; Zabeti, A; Zhou, X, 2018)
"Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and -10 and exhibits possible neuroprotective properties."	2.82	Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. ( Agius, M; Ashokkumar, A; Bashir, K; Bermel, R; Coffey, CS; Cohen, B; Conwit, R; Coyle, P; Cudkowicz, ME; Delgado, S; Dewitt, D; Ecklund, D; Flores, A; Fox, RJ; Giesser, B; Gleason, T; Goldman, M; Goodman, A; Jubelt, B; Klawiter, EC; Koepp, M; Lava, N; Long, J; Lynch, S; Matsuda, K; McGovern, M; Miravalle, A; Moses, H; Naismith, R; Natarajan, S; Ontaneda, D; Perumal, J; Racke, M; Ramachandran, S; Repovic, P; Riley, C; Severson, C; Shinnar, S; Skaramagas, T; Suski, V; Thornell, B; Weinstock-Gutman, B; Yadav, V; Yankey, J; Zabeti, A, 2016)
"Treatment with ibudilast was generally safe and well tolerated."	2.75	Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? ( Barkhof, F; Drulovic, J; Hulst, HE; Landin, R; Matsuda, K; Uitdehaag, BM, 2010)
"Ibudilast is a nonselective phosphodiesterase inhibitor which works by blocking the cleavage of cyclic adenosine monophosphate (cAMP)."	2.53	Ibudilast for the treatment of multiple sclerosis. ( Goodman, AD; Gyang, T; Smith, AD, 2016)

Research

Studies (6)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Covariate-adjusted Mean Rate of Change in Brain Atrophy Over 96 Weeks as Measured by Brain Parenchymal Fraction (BPF).

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	6 (100.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Maillart, E	1
Fox, RJ	2
Coffey, CS	2
Conwit, R	2
Cudkowicz, ME	2
Gleason, T	2
Goodman, A	2
Klawiter, EC	2
Matsuda, K	3
McGovern, M	2
Naismith, RT	1
Ashokkumar, A	2
Barnes, J	1
Ecklund, D	2
Klingner, E	1
Koepp, M	2
Long, JD	1
Natarajan, S	2
Thornell, B	2
Yankey, J	2
Bermel, RA	1
Debbins, JP	1
Huang, X	1
Jagodnik, P	1
Lowe, MJ	1
Nakamura, K	1
Narayanan, S	1
Sakaie, KE	1
Thoomukuntla, B	1
Zhou, X	1
Krieger, S	1
Alvarez, E	1
Apperson, M	1
Bashir, K	2
Cohen, BA	1
Coyle, PK	1
Delgado, S	2
Dewitt, LD	1
Flores, A	2
Giesser, BS	1
Goldman, MD	1
Jubelt, B	2
Lava, N	2
Lynch, SG	1
Moses, H	2
Ontaneda, D	2
Perumal, JS	1
Racke, M	2
Repovic, P	2
Riley, CS	1
Severson, C	2
Shinnar, S	2
Suski, V	2
Weinstock-Guttman, B	1
Yadav, V	2
Zabeti, A	2
Goodman, AD	1
Gyang, T	1
Smith, AD	1
Naismith, R	1
Bermel, R	1
Long, J	1
Ramachandran, S	1
Skaramagas, T	1
Agius, M	1
Cohen, B	1
Coyle, P	1
Dewitt, D	1
Giesser, B	1
Goldman, M	1
Lynch, S	1
Miravalle, A	1
Perumal, J	1
Riley, C	1
Weinstock-Gutman, B	1
Dolgin, E	1
Barkhof, F	1
Hulst, HE	1
Drulovic, J	1
Uitdehaag, BM	1
Landin, R	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Activity of Ibudilast (MN-166) in Subjects With Progressive Multiple Sclerosis[NCT01982942]	Phase 2	255 participants (Actual)	Interventional	2013-11-30	Completed
Regeneration in Cervical Degenerative Myelopathy - a Multi-centre, Double-blind, Randomised, Placebo Controlled Trial Assessing the Efficacy of Ibudilast as an Adjuvant Treatment to Decompressive Surgery for Degenerative Cervical Myelopathy[NCT04631471]	Phase 3	400 participants (Anticipated)	Interventional	2021-12-22	Recruiting
A Multi-Center, Open-Label Biomarker Study to Evaluate MN-166 (Ibudilast) in Subjects With Amyotrophic Literal Sclerosis (ALS)[NCT02714036]	Phase 1/Phase 2	35 participants (Actual)	Interventional	2016-05-06	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

To evaluate the activity of ibudilast (100 mg/day) versus placebo at 96 weeks as measured by quantitative magnetic resonance imaging (MRI) analysis for whole brain atrophy using brain parenchymal fraction (BPF), calculated as the ratio of brain parenchymal tissue volume to the total volume contained within the brain surface contour. (NCT01982942)
Timeframe: 96 weeks

Magnetization Transfer Ratio (MTR) Imaging in Normal-appearing Brain Tissue

Intervention	ratio (Mean)
Ibudilast	-0.00168
Placebo Oral Capsule	-0.00392

A magnetization transfer MRI as a marker of brain myelin content including the cerebral cortex could be useful. MT imaging provides access to the restricted protons, which are located in biologically interesting tissue regions.Cortical and normal appearing grey matter MTR correlates strongly with measures of disability such as the multiple sclerosis functional composite score and can show treatment effects. (NCT01982942)
Timeframe: 96 weeks

New T1 Lesions Since Baseline

Intervention	ratio (Least Squares Mean)
Ibudilast	0.325
Placebo Oral Capsule	0.247

New T1 lesions since baseline as measured by least square mean (90% confidence interval). (NCT01982942)
Timeframe: 96 weeks

Percentage of Participants With Adverse Events.

Intervention	lesions (Least Squares Mean)
Ibudilast	0.355
Placebo Oral Capsule	0.317

Safety Measures: percentage of participants who experienced treatment-emergent adverse events, clinically significant abnormal laboratory and electrocardiogram results. (NCT01982942)
Timeframe: 96 weeks

Retinal Nerve Fiber Layer as Measured by Optical Coherence Tomography (OCT).

Intervention	percentage receiving study medication (Number)
Ibudilast	92.2
Placebo Oral Capsule	88.1

Mean retinal nerve fiber layer thickness from baseline measured by Optical coherence tomography (OCT), a non-invasive imaging technique used to obtain high-resolution cross-sectional images of the retina. Increase in thickness is considered improvement. (NCT01982942)
Timeframe: 96 weeks

Diffusion Tensor Imaging (DTI) in Descending Pyramidal White Matter Tracts

Intervention	micrometers (Least Squares Mean)
Ibudilast	83.0
Placebo Oral Capsule	79.5

Diffusion tensor imaging estimates the three-dimensional diffusion of water in brain tissue and has been explored as an outcome in MS. (NCT01982942)
Timeframe: 48 weeks

Intervention	10^3/mm^2/s (Least Squares Mean)
	Left axial diffusivity mean	Left radial diffusivity mean	Right axial diffusivity mean	Right radial diffusivity mean
Ibudilast	0.0001	-0.0077	0.0014	-0.0029
Placebo Oral Capsule	-0.0006	0.0027	-0.0017	0.0046

Article	Year
Treatment of progressive multiple sclerosis: Challenges and promising perspectives. Revue neurologique, 2018, Volume: 174, Issue:6 Topics: Anti-Inflammatory Agents; Disease Progression; Humans; Multiple Sclerosis; Neurology; Pyridines	2018
Ibudilast for the treatment of multiple sclerosis. Expert opinion on investigational drugs, 2016, Volume: 25, Issue:10 Topics: Animals; Anti-Inflammatory Agents; Brain; Disease Progression; Humans; Multiple Sclerosis; Neuroprot	2016

Article	Year
Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis. The New England journal of medicine, 2018, 08-30, Volume: 379, Issue:9 Topics: Adult; Atrophy; Brain; Depression; Diffusion Tensor Imaging; Disease Progression; Double-Blind Metho	2018
Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. Contemporary clinical trials, 2016, Volume: 50 Topics: Adult; Brain; Diffusion Tensor Imaging; Disease Progression; Double-Blind Method; Humans; Middle Age	2016
Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? Neurology, 2010, Mar-30, Volume: 74, Issue:13 Topics: Adult; Brain; Disability Evaluation; Disease Progression; Double-Blind Method; Female; Humans; Magne	2010
Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? Neurology, 2010, Mar-30, Volume: 74, Issue:13 Topics: Adult; Brain; Disability Evaluation; Disease Progression; Double-Blind Method; Female; Humans; Magne	2010
Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? Neurology, 2010, Mar-30, Volume: 74, Issue:13 Topics: Adult; Brain; Disability Evaluation; Disease Progression; Double-Blind Method; Female; Humans; Magne	2010
Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? Neurology, 2010, Mar-30, Volume: 74, Issue:13 Topics: Adult; Brain; Disability Evaluation; Disease Progression; Double-Blind Method; Female; Humans; Magne	2010

ibudilast and Disease Exacerbation