Memantine for the long term management of neuropsychiatric symptoms in Alzheimer's disease

ISRCTN	ISRCTN68407918
DOI	https://doi.org/10.1186/ISRCTN68407918
Secondary identifying numbers	Protocol Version 4, 8/7/2007

Submission date: 08/01/2008
Registration date: 14/02/2008
Last edited: 20/06/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Clive Ballard
Scientific

Wolfson Centre for Age-Related Diseases
Wolfson Wing
Hodgkin Building
King's College London
Guy's Campus
London
SE1 1UL
United Kingdom

Phone	+44 20 7848 8054
Email	clive.ballard@kcl.ac.uk

Study information

Study design	Multi-centre double-blind placebo-controlled double-dummy parallel-group randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised parallel trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Memantine for the Long Term Management of Neuropsychiatric Symptoms in Alzheimer's disease (MAIN-AD)
Study acronym	MAIN-AD
Study objectives	The principal research objective is to investigate the efficacy and safety of memantine when compared to neuroleptics in the long-term management of neuropsychiatric symptoms in people with Alzheimer's disease.
Ethics approval(s)	Multi-centre Research Ethics Committee for Wales, 28/03/2008, ref: 08/MRE09/5
Health condition(s) or problem(s) studied	Alzheimer's disease
Intervention	Intervention group: Memantine + placebo neuroleptic for 24 weeks Control group: Neuroleptic + placebo memantine for 24 weeks The choice of neuroleptic and dose will be made by the responsible clinician. The neuroleptics allowed are haloperidol, risperidone, olanzapine and quetiapine.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Memantine
Primary outcome measure	The following will be assessed at baseline, week 6, week 12 and week 24: 1. Bristol Activities of Daily Living scale. Please note that only the week 24 outcome will be considered as the primary outcome. 2. Cohen-Mansfield agitation inventory.
Secondary outcome measures	The following will be assessed at baseline, week 6, week 12 and week 24: 1. Neuropsychiatric inventory 2. Severe impairment battery 3. Mini-mental state examination 4. Letter fluency (FAS) test 5. Functional assessment staging 6. Modified D test 7. Clinical global impression of change 8. Modified unified Parkinson's disease rating scale 9. Abnormal involuntary movement scale
Overall study start date	01/04/2008
Completion date	01/06/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	300
Key inclusion criteria	1. Living in a nursing or social care facilities 2. Fulfill the National Institute of Neurological and Communication Disorders and Stroke/ Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for possible or probable Alzheimer's Disease (AD) 3. Taking at least 0.5 mg daily of haloperidol, 0.5 mg daily of risperidone, 5 mg daily of olanzapine or 25 mg daily of quetiapine or another neuroleptic which in the opinion of the responsible clinician could be safely converted to one of these neuroleptics, for a minimum of 3 months prior to entry into the study 4. If taking a cholinesterase inhibitor, prescribed for at least 6 months before the date of assessment, with a stable dose for at least 3 months 5. Not taking anticonvulsants other than carbamazepine or sodium valproate. The use of either of these 2 agents is permissible if the dose has been stable for at least 4 weeks 6. If taking any other psychotropic drugs (e.g., antidepressants, benzodiazepines, chlormethiazole), the dose has been stable for at least 4 weeks prior to randomization 7. Have not received memantine in the last 6 weeks 8. Taking any medications that are contra-indicated or not recommended in combination with memantine, as defined in the British National Formulary, including ketamine, dextromethorphan and amantidine 9. Written informed consent provided by the participant (if they have capacity) and/or their next of kin or a legal representative
Key exclusion criteria	1. Current evidence of delirium 2. Moderately severe renal impairment, as measured by or equivalent to an estimated creatinine clearance of <50 mL/min/1.73 m2 3. Severe hepatic impairment 4. Unable to swallow tablets or capsules 5. Low probability of treatment compliance 6. Currently taking memantine 7. Previous evidence of lack of efficacy or tolerability to memantine 8. Taking any of the following substances: 8.1. An investigational drug during the 4 weeks prior to randomization 8.2. A drug known to cause major organ system toxicity during the 4 weeks prior to randomization. 8.3. Started any new psychotropic medication during the 4 weeks prior to randomization. Participants who have been on a stable dose of psychotropic during the 4 weeks prior to randomization are still eligible 8.4. Memantine during the 6 weeks prior to randomization 8.5. Other N-methyl-D-aspartate (NMDA) antagonists: amantadine, ketamine, and dextromethorphan. 8.6. Barbiturates and primidone 8.7. Baclofen and dantrolen 8.8. Dextromethorphan 8.9. Antimuscarinics 8.10. Anticonvulsants other than sodium valproate or carbamazepine. These 2 agents are permissible if doses have been stable for at least 4 weeks
Date of first enrolment	01/04/2008
Date of final enrolment	01/06/2010

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

King's College London

London
SE1 1UL
United Kingdom

Sponsor information

King's College London (UK)
University/education

Hodkin Building
Guy's Campus
London
SE1 1UL
England
United Kingdom

Website	http://kcl.ac.uk
"ROR"	https://ror.org/0220mzb33

Funders

Funder type

Industry

Lundbeck Pharmaceutical (Contact: Dr Ya'acov Leigh, Lundbeck House, Caldecotte Lake Business Park, Caldecotte, Milton Keynes, MK7 8LG, UK. E-mail: YALE@lundbeck.com)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/04/2015		Yes	No

Editorial Notes

20/06/2016: Publication reference added.