Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial.
Aged
Andrographis
Anti-Inflammatory Agents, Non-Steroidal
/ pharmacology
Brain
/ diagnostic imaging
Disease Progression
Diterpenes
/ pharmacology
Double-Blind Method
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
/ drug therapy
Phytotherapy
Pilot Projects
Prospective Studies
Andrographolide
Brain atrophy
Disability progression
Multiple sclerosis
Progressive multiple sclerosis
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
07 May 2020
07 May 2020
Historique:
received:
05
03
2020
accepted:
23
04
2020
entrez:
9
5
2020
pubmed:
10
5
2020
medline:
18
9
2020
Statut:
epublish
Résumé
Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS. A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change. Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was - 0.679% for the AP group and - 1.069% for the placebo group (mean difference: -0.39; 95% CI [- 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was - 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia. AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial. ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.
Sections du résumé
BACKGROUND
BACKGROUND
Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS.
METHODS
METHODS
A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change.
RESULTS
RESULTS
Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was - 0.679% for the AP group and - 1.069% for the placebo group (mean difference: -0.39; 95% CI [- 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was - 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia.
CONCLUSIONS
CONCLUSIONS
AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.
Identifiants
pubmed: 32380977
doi: 10.1186/s12883-020-01745-w
pii: 10.1186/s12883-020-01745-w
pmc: PMC7203851
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Diterpenes
0
andrographolide
410105JHGR
Banques de données
ClinicalTrials.gov
['NCT02273635']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
173Subventions
Organisme : Corporación de Fomento de la Producción
ID : 14PIE-26946
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