Minocycline in Alzheimer’s Disease Efficacy (MADE) Trial

Conditions

Alzheimer's Disease MedDRA version: 18.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852

Robert Howard, Olga Zubko, Richard Gray, Rosie Bradley, Emma Harper et al. (21 authors)

Efficacy and Mechanism Evaluation2020-04-0117 citations

10.3310/eme07020

Minocycline at 2 Different Dosages vs Placebo for Patients With Mild Alzheimer Disease

Robert Howard, Olga Zubko, Rosie Bradley, Emma Harper, Lynn Pank et al. (21 authors)

JAMA Neurology2019-11-18176 citations

10.1001/jamaneurol.2019.3762

Interventions

Trade Name: Acnamino MR 100mg capsules Pharmaceutical Form: Capsule, hard INN or Proposed INN: minocycline hydrochloride CAS Number: 13614-98-7

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Diagnosis of possible or probable AD by NIA/AA criteria (McKhann et al 2011). • sMMSE score >23 with no upper limit. • Giving informed consent to participate. • Aged 50+ • Participants must have a potential informant who will assist in the administration of the BADLS Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 560 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 560

Exclusion criteria

Exclusion criteria: • Known allergy to tetracycline antibiotics. • 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. • Uncontrolled serious concomitant illness • Known chronic kidney disease stages 3b-5 • Moderate liver disease (see Child-Pugh for Classification of Severity of Liver Disease) • Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator. • Withholds consent for the study team to inform his/her GP • Systemic Lupus Erythromatosus (SLE). • Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days.

Design outcomes

Primary

Measure	Time frame
Main Objective: To determine whether minocycline is superior to placebo in slowing the disease course of early AD, over a 2-year period, measured by reduced rate of decline in: (i) Cognition. (ii) Function. ; Secondary Objective: The secondary objectives of MADE are: (i) To compare the safety and tolerability of minocycline at doses of 400mg/day and 200mg/day (ii) To determine whether 400mg/day offer superior neuroprotection to 200mg/day. (iii) To investigate associated risks of side-effects and serious adverse events. (iv) To estimate the magnitude of any statistically significant positive treatment effects on cognitive and functional decline and thereby inform the design and powering of a future phase III trial of definitive clinical effectiveness within the NHS. ; Primary end point(s): (i) Cognitive function measured by the Standardised Mini-Mental State Examination (ii) Functional ability measured with the Bristol Activities of Daily Living Scale ;Timepoint(s) of evaluation of this end point: 6, 12, 18 and 24 months	—

Measure

Time frame

Main Objective: To determine whether minocycline is superior to placebo in slowing the disease course of early AD, over a 2-year period, measured by reduced rate of decline in: (i) Cognition. (ii) Function. ; Secondary Objective: The secondary objectives of MADE are: (i) To compare the safety and tolerability of minocycline at doses of 400mg/day and 200mg/day (ii) To determine whether 400mg/day offer superior neuroprotection to 200mg/day. (iii) To investigate associated risks of side-effects and serious adverse events. (iv) To estimate the magnitude of any statistically significant positive treatment effects on cognitive and functional decline and thereby inform the design and powering of a future phase III trial of definitive clinical effectiveness within the NHS. ; Primary end point(s): (i) Cognitive function measured by the Standardised Mini-Mental State Examination (ii) Functional ability measured with the Bristol Activities of Daily Living Scale ;Timepoint(s) of evaluation of this end point: 6, 12, 18 and 24 months

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Secondary

Measure	Time frame
Secondary end point(s): i) Blood monitoring of haematopoetic, renal and hepatic function will be carried out every 6 months ii)documentation of skin reactions, gastrointestinal and neurological symptoms ; Timepoint(s) of evaluation of this end point: i) 6, 12, 18, 24 months ii) every 3 months	—

Countries

United Kingdom

Contacts

Public ContactRobert Howard

King's College London

robert.j.howard@kcl.ac.uk4402078480545

Outcome results

None listed