Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial
Abstract 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 di...
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | BMC Neurology |
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| Online Access: | http://link.springer.com/article/10.1186/s12883-020-01745-w |
| _version_ | 1818478702303903744 |
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| author | Ethel Ciampi Reinaldo Uribe-San-Martin Claudia Cárcamo Juan Pablo Cruz Ana Reyes Diego Reyes Carmen Pinto Macarena Vásquez Rafael A. Burgos Juan Hancke |
| author_facet | Ethel Ciampi Reinaldo Uribe-San-Martin Claudia Cárcamo Juan Pablo Cruz Ana Reyes Diego Reyes Carmen Pinto Macarena Vásquez Rafael A. Burgos Juan Hancke |
| author_sort | Ethel Ciampi |
| collection | DOAJ |
| description | Abstract 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 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 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 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 ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014. |
| first_indexed | 2024-12-10T09:51:19Z |
| format | Article |
| id | doaj.art-151ec85904924bac8b1cbb4206524f3f |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-12-10T09:51:19Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-151ec85904924bac8b1cbb4206524f3f2022-12-22T01:53:39ZengBMCBMC Neurology1471-23772020-05-0120111010.1186/s12883-020-01745-wEfficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trialEthel Ciampi0Reinaldo Uribe-San-Martin1Claudia Cárcamo2Juan Pablo Cruz3Ana Reyes4Diego Reyes5Carmen Pinto6Macarena Vásquez7Rafael A. Burgos8Juan Hancke9Neurology Department, Faculty of Medicine, Pontificia Universidad Católica de ChileNeurology Department, Faculty of Medicine, Pontificia Universidad Católica de ChileNeurology Department, Faculty of Medicine, Pontificia Universidad Católica de ChileRadiology, Pontificia Universidad Católica de ChileNeurology Department, Faculty of Medicine, Pontificia Universidad Católica de ChileNeurology Department, Faculty of Medicine, Pontificia Universidad Católica de ChileNeurology Department, Faculty of Medicine, Pontificia Universidad Católica de ChileNeurology Department, Faculty of Medicine, Pontificia Universidad Católica de ChilePharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de ChilePharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de ChileAbstract 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 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 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 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 ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.http://link.springer.com/article/10.1186/s12883-020-01745-wMultiple sclerosisProgressive multiple sclerosisAndrographolideBrain atrophyDisability progression |
| spellingShingle | Ethel Ciampi Reinaldo Uribe-San-Martin Claudia Cárcamo Juan Pablo Cruz Ana Reyes Diego Reyes Carmen Pinto Macarena Vásquez Rafael A. Burgos Juan Hancke Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial BMC Neurology Multiple sclerosis Progressive multiple sclerosis Andrographolide Brain atrophy Disability progression |
| title | Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial |
| title_full | Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial |
| title_fullStr | Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial |
| title_full_unstemmed | Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial |
| title_short | Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial |
| title_sort | efficacy of andrographolide in not active progressive multiple sclerosis a prospective exploratory double blind parallel group randomized placebo controlled trial |
| topic | Multiple sclerosis Progressive multiple sclerosis Andrographolide Brain atrophy Disability progression |
| url | http://link.springer.com/article/10.1186/s12883-020-01745-w |
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