Minocycline 200 mg or 400 mg versus placebo for mild Alzheimer’s disease: the MADE Phase II, three-arm RCT
| Autor: | Robert Howard, Olga Zubko, Richard Gray, Rosie Bradley, Emma Harper, Linda Kelly, Lynn Pank, John O’Brien, Chris Fox, Naji Tabet, Gill Livingston, Peter Bentham, Rupert McShane, Alistair Burns, Craig Ritchie, Suzanne Reeves, Simon Lovestone, Clive Ballard, Wendy Noble, Gordon Wilcock, Ramin Nilforooshan |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Efficacy and Mechanism Evaluation, Vol 7, Iss 2 (2020) |
| Druh dokumentu: | article |
| ISSN: | 2050-4365 2050-4373 |
| DOI: | 10.3310/eme07020 |
| Popis: | Background: Minocycline is an anti-inflammatory drug and protects against the toxic effects of β-amyloid in vitro and in animal models of Alzheimer’s disease. To the best of our knowledge, no randomised placebo-controlled clinical trials in patients with Alzheimer’s disease looking at the efficacy and tolerability of minocycline have been carried out. Objectives: The trial investigated whether or not minocycline was superior to placebo in slowing down the rate of decline in cognitive and functional ability over 2 years. The safety and tolerability of minocycline were also assessed. Design: A Phase II, three-arm, randomised, double-blind, multicentre trial with a semifactorial design. Participants continued on trial treatment for up to 24 months. Setting: Patients were identified from memory services, both within the 32 participating NHS trusts and within the network of memory services supported by the Dementias and Neurodegenerative Diseases Research Network (also known as DeNDRoN). Participants: Patients with standardised Mini Mental State Examination scores of > 23 points and with Alzheimer’s disease assessed by the National Institute on Aging–Alzheimer’s Association’s criteria were identified from memory services. Intervention: Patients with mild Alzheimer’s disease were randomly allocated 1 : 1 : 1 to receive one of three treatments: arm 1 – 400 mg per day of minocycline; arm 2 – 200 mg per day of minocycline; or arm 3 – placebo. Patients continued treatment for 24 months. Participants, investigators and outcome assessors were blind to treatment allocation. Main outcome measures: Primary outcome measures were decline in standardised Mini Mental State Examination and Bristol Activities of Daily Living Scale scores of combined minocycline treatment arms versus placebo, as analysed by intention-to-treat repeated measures regression. Results: Between 23 May 2014 and 14 April 2016, 554 participants were randomised. Of the 544 eligible participants, the mean age was 74.3 years and the average standardised Mini Mental State Examination score was 26.4 points. A total of 252 serious adverse events were reported, with the most common categories being neuropsychiatric and cardiocirculatory. Significantly fewer participants completed treatment with 400 mg of minocycline [29% (53/184)] than 200 mg [62% (112/181)] or placebo [64% (114/179)] (p |
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