Phase III, randomised, double-blind, placebo-controlled trial of Neuroaspis plp10 as an adjuvant treatment for relapsing multiple sclerosis: the MINERAL Study.

Objectives: To assess the effectiveness of Neuroaspis plp10 nutritional supplement when added to interferon (IFN)-β treatment in patients with relapsing-remitting multiple sclerosis (RRMS).
Design: A 30-month phase III multicentre, randomised, double-blind, placebo-controlled trial. Randomisation stratified by centre using a computer-generated procedure with Neuroaspis plp10 versus placebo in 1:1 ratio. The first 6 months were used as both the pre-entry and normalisation period.
Setting: 3 teaching hospitals in Greece and 1 Neurology Institute in Cyprus.
Participants: 61 patients with RRMS on IFN-β were randomly assigned to receive Neuroaspis plp10 (n=32) or placebo (n=29), 20 mL, orally, once daily, for 30 months.
Intervention: Neuroaspis plp10, a cocktail mixture, containing specific PUFA (12 150 mg) and γ-tocopherol (760 mg) versus virgin olive oil (placebo).
Main Outcome Measure: The primary end point was the annual relapse rate (ARR) whereas the secondary ones were the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale (EDSS) and the brain T2 and gadolinium-enhancing lesions, at 2 years.
Results: For the intention-to-treat analyses Neuroaspis plp10 significantly reduced the ARR by 80%, (RRR, 0.20; 95% CI: 0.09 to 0.45; p=0.0001) and the risk of sustained progression of disability by 73% (HR, 0.27; 95% CI: 0.09 to 0.83; p=0.022) versus placebo, at 2 years. The number of T1 gadolinium-enhancing lesions and the number of new/enlarged T2-hyperintense lesions were significantly reduced (p=0.01 and p<0.0001, respectively). Both T1-enhancing and new/enlarging T2-hyperintense lesions were significantly reduced (p=0.05 and p<0.0001, respectively). No significant adverse events were reported.
Conclusions: Neuroaspis plp10 added to IFN-β was significantly more effective than IFN-β alone in patients with RRMS.
Trial Registration Number: ISRCTN06166891.
Competing Interests: Competing interests: MCP, GL, IP received grand support from the Cyprus Ministry of Energy, Commerce, Industry and Tourism—Structural Funds Program (Creation of New High Technology and Innovation Enterprises). PALUPA Medical is a research company formed and registered under the Incubator program. MCP, GL and IP are stockholders of PALUPA Medical. MAR received speaker honoraria from Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche and Teva, and receives research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla. NG received speaker honoraria from Bayer, Biogen, Gensis Pharma, Celgene, Sanofi, Merck, Novartis, Roche and Teva, and receives research support from Biogen and TEVA. CB received travel support and/or lecture fees from Novartis, Merck, Genesis, Sanofi, Teva, Roche and Mylan. GH, ED, EN, GM, SO, PV, RM and PP declare no competing interests. No pharmaceutical companies were involved in this project. The intervention, trade marked as Neuroaspis plp10, is under a US patent application, and covered with granted patent in several other countries including Canada, Japan, China, Ukraine, Australia, Israel and New Zealand.
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