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 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 140mg 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

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches

“…Intriguingly, andrographolide has been reported to have a potential neuroprotective effect on CCH‐induced hippocampal neuronal damage and cognitive impairment by inhibiting astrocyte activation and enhancing BDNF TrkB signaling pathway (Wang et al, 2019). A prospective randomized controlled trial of andrographolide in the treatment of inactive progressive multiple sclerosis evidenced that, it has potential research significance in reducing brain atrophy and disability and showed a well‐tolerated by patients, but needs to be further evaluated in larger clinical trials (Ciampi et al, 2020). Besides, andrographolide also delineated excellent effect in protecting hippocampal neurons from injury (Wang et al, 2020) and relieving neuropathic pain (Yi et al, 2018).…”

“…By analyzing the literatures, it was conjectural that the toxicity of andrographolide was mainly related to the concentration and time of administration. Besides, a clinical trial of andrographolide 140 mg orally twice a day in the treatment of multiple sclerosis demonstrated that it caused mild rash and taste disorder, which executor suggested it need to be further evaluated in a larger clinical trial (Ciampi et al, 2020). More interestingly, in a phase I clinical study of andrographolide in the treatment of HIV, andrographolide was reported to cause mild to moderate headache, fatigue, rash, decreased taste, large diarrhea or pruritus and allergic reactions (Calabrese et al, 2000).…”