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Minocycline in Alzheimer's Disease (MADE)

This trial aims to determine whether minocycline is superior to placebo in affecting the disease course over a two-year period in patients with very early Alzheimer’s Disease (AD). Researchers will measure whether the drug is effective in reducing the rate of decline in cognitive and functional outcomes as measured by the Standardised Mini-Mental State Examination (SMMSE) and Bristol Activities of Daily Living Scale (BADLS) respectively.  

The trial will also assess the safety and tolerability of minocycline using standard tests of haematopoetic, renal and hepatic function as well as documentation of skin reactions, gastrointestinal and neurological symptoms. 

Why carry out the research? 

AD is a major public health issue and the imperative to discover and develop treatments that can stop or at least delay disease progression is clear. Symptomatic AD treatments in the form of cholinesterase inhibitors and memantine have been the mainstay of current treatment for more than ten years, but do not slow progression of the disease.  

There is a substantial body of evidence to indicate that minocycline may be neuroprotective in neurodegenerative diseases such as AD. Although the primary neuroprotective target of minocycline in the central nervous system is not known, the principal effects of minocycline include the inhibition of microglial activation, attenuation of apoptosis and suppression of the production of reactive oxygen species. Minocycline is arguably the most promising off-patent candidate for AD modification that is not currently in trials and is cheap and well tolerated. The time is now right for an adequately powered clinical trial, conducted for a sufficiently long period to demonstrate efficacy on simple cognitive and functional outcomes.  

The results, even if clearly negative, will move the field on to a significant degree. If minocycline treatment does not influence cognitive and functional change over two years, this will end serious interest in the drug as an AD treatment. But, if differences greater than those considered to represent minimum clinically important differences for AD therapies are seen, this will rapidly pave the way for Phase III effectiveness trials supported by the Health Technology Assessment (HTA). 

How is the research being undertaken? 

This is a multi-centre, randomised, double-blind, placebo-controlled, semi-factorial (2x1) design, phase II clinical trial. 480 patients, with very mild AD will be recruited from Memory Services within participating sites across the country. Eligible patients will be randomly assigned to one of three treatment arms: 

  • Arm 1 - Minocycline 400mg/day 
  • Arm 2 - Minocycline 200mg/day 
  • Arm 3 - Placebo 

Treatment will continue daily for 24 months. During the course of the trial, researchers will assess the cognitive and functional outcomes as well as safety and tolerability of the drug. 

Where is it happening? 

Currently there are 27 participating sites across England and Scotland and others may join during the course of the trial. 


The trial is funded by the Efficacy and Mechanism Evaluation Programme award (NIHR).