Minocycline in Alzheimer's Disease (MADE)
This trial aims to determine whether minocycline is superior to placebo in affecting the disease course over a 2-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?
How is the research being undertaken?
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 10 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 absolutely 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 2 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).
Where is it happening?
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.
Who is involved?
Currently there are 27 participating sites across England and Scotland and others may join during the course of the trial.
What is the timescale?
Professor Robert Howard in the Department of Old Age Psychiatry is the Chief Investigator.
Dr Suzanne Reeves and Professor Simon Lovestone are Co-Investigators.
The trial is funded by the Efficacy and Mechanism Evaluation Programme award (NIHR).
Recruitment is due to begin in January 2014 and the trial will continue until December 2017.
To find out more please contact:-
Dr Olga Zubko (Project Manager)