Plain English Summary
Background and study aims
Alzheimers disease (a mental disorder) is a major public health issue and there is a clear need to discover and develop treatments that can stop or at least delay disease progression. Unfortunately, although we have drug treatments that can reasonably improve some of the symptoms of Alzheimer's disease, we do not yet have treatments that can slow down or stop deterioration. Minocycline is an antibiotic drug that has also been shown to slow down deterioration in some research using animal models. This makes it the most promising drug for treatment that is not currently in trials and it is cheap and well tolerated. This study will find out the effects of two years of minocycline treatment on deterioration in mental processes and activities of daily living in patients with early Alzheimer's disease assessed and managed within NHS Memory Services. If minocycline can be shown to be working well, this would rapidly pave the way for further studies and ultimately the availability of a low cost and safe treatment for this common and devastating condition.
Who can participate?
Any patient aged 50 or over, diagnosed with Alzheimer's disease, can participate in this study.
What does the study involve?
Participants will be randomly allocated to one of three groups: daily treatment with 400 mg minocycline, 200 mg minocycline or a dummy drug (placebo). They will undergo this treatment for two years.
What are the possible benefits and risks of participating?
It is possible that minocycline may slow the rate of progression of disease or reduce symptoms of Alzheimers disease, but this cannot be guaranteed. Participation will provide useful information about the disease and minocycline. It is possible that patients may experience side effects from taking the study drug. These side effects may include nausea, diarrhoea and dizziness. Rarely the drug can cause increased sensitivity to sunlight and, very rarely, joint pain. In addition, there is always a risk of unknown side effects occurring.
Where is the study run from?
The study is run across 20 sites in England and Scotland.
When is study starting and how long is it expected to run for?
The study started in June 2013 and will run until 2018.
Who is funding the study?
The study is funded by the National Institute of Health Research (NIHR), UK.
Who is the main contact?
Dr Olga Zubko
olga.zubko@kcl.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Olga Zubko
ORCID ID
Contact details
16 De Crespigny Park
London
SE5 8AF
United Kingdom
-
olga.zubko@kcl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
14866; 11/47/01
Study information
Scientific title
The MADE Trial: Minocycline in Alzheimer's Disease Efficacy trial
Acronym
MADE
Study hypothesis
The MADE Trial will examine the effects of two years of minocycline treatment on deterioration in cognitive function and activities of daily living in patients with early Alzheimer's disease assessed and managed within NHS Memory Services. If minocycline can be shown to have efficacy in the trial, this would rapidly pave the way for effectiveness trials and ultimately availability of a low cost and safe treatment for this common and devastating condition.
Ethics approval
London South REC, ref: 13//EE/0063
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Dementias and Neurodegenerative Diseases Research Network; Subtopic: Dementia; Disease: Alzheimer's Disease
Intervention
Drug Treatment. Participants will be allocated to one of three treatment arms:
1. Minocycline 400mg/day
2. Minocycline 200mg/day
3. Placebo
They will take the allocated treatment orally for a period of two years.
Intervention type
Drug
Phase
Not Specified
Drug names
Minocycline
Primary outcome measure
To determine whether minocycline is superior to placebo; Timepoint(s): Baseline and 2 years
1. Cognition will be measured using sMMSE
2. Functional ability will be measured using Bristol Activities of Daily Living Scale (BADLS)
Secondary outcome measures
Not provided at time of registration
Overall trial start date
01/06/2013
Overall trial end date
31/05/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Diagnosis by National Institute on Aging (NIA)/ Alzheimer's Association (AA) criteria of possible or probable Alzheimer's Disease (McKhann et al 2011)
2. Standardized Mini-Mental State Examination (SMMSE) score >23 with no upper limit
3. Consenting to participate
Target Gender: Male & Female; Upper Age Limit 100 no age limit or unit specified ; Lower Age Limit 45 no age limit or unit specified
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
Planned Sample Size: 480; UK Sample Size: 480
Participant exclusion criteria
1. Known allergy to tetracycline antibiotics
2. Diagnosis of mild cognitive impairment
3. Female of childbearing potential. Patients must be surgically sterile (hysterectomy, bilateral salpingectomy/oophorectomy) for at least 6 months minimum or have undergone bilateral tubal occlusion/ligation at least 6 months prior or have been post-menopausal for at least 1 year.
4. Pregnancy and lactation.
5. Known chronic kidney disease stages 3-5
6. Lacks capacity to give informed consent
7. Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator. Patients with creatinine clearance < 50 mL/min at Screening, according to the Cockcroft and Gault equation must be excluded.
8. Systemic Lupus Erythromatosis
9. Severe liver disease
10. Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days
Contraindications, warnings and special precautions to minocycline use are not described further in the protocol and the investigator should refer to the Summary of Product Characteristics http://emc.medicines.org.uk/.
Recruitment start date
01/06/2013
Recruitment end date
31/05/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
16 De Crespigny Park
London
SE5 8AF
United Kingdom
Funders
Funder type
Government
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Funder name
Efficacy and Mechanism Evaluation Programme; Grant Codes: 11/47/01
Alternative name(s)
NIHR Efficacy and Mechanism Evaluation Programme, EME
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list