Memantine for the Long Term Management of Neuropsychiatric Symptoms in Alzheimer's disease - MAIN-AD - MAIN-AD

• Register: EUCTR
• Last refreshed on: 4 December 2018
• Main ID: EUCTR2007-004897-26-GB
• Date of registration: 28/03/2008
• Prospective Registration: Yes
• Primary sponsor: King's College London
• Public title: Memantine for the Long Term Management of Neuropsychiatric Symptoms in Alzheimer's disease - MAIN-AD - MAIN-AD
• Scientific title: Memantine for the Long Term Management of Neuropsychiatric Symptoms in Alzheimer's disease - MAIN-AD - MAIN-AD
• Date of first enrolment: 23/05/2008
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004897-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
• Living: in a nursing or social care facilities.
• Fulfil the NINCDS/ADRDA criteria for possible or probable Alzheimer's disease (AD).
• Taking at least 0.5mg daily of haloperidol, 0.5mg daily of risperidone, 5mg daily of olanzapine or 25mg 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.
• 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.
• 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.
• If taking any other psychotropic drugs (eg antidepressants, benzodiazepines, chlormethiazole), the dose has been stable for at least 4 weeks prior to randomization.
• Not receiving treatment with memantine or have taken memantine in the past 6 weeks, and responsible clinician not considering treatment with memantine.
• MMSE score =3 and =15.

• Not taking any medications that are contra-indicated or not recommended in combination with memantine, as defined in the British National Formulary, including ketamine, dextromethorphan, amantidine.
• Written informed consent provided by the participant’s next of kin or a legal representative.


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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Clinician responsible for care, or study clinician considers that the patient suffers from any physical condition (including marked extra-pyramidal disorder), which would make participation in the trial distressing or likely to increase suffering.
• Patients with a systolic blood pressure whilst sitting greater than 180 mm/Hg or less than 90 mm/Hg, or a diastolic blood pressure whilst sitting greater than 100 mm/Hg or less than 50 mm/Hg at the screening visits or baseline.
• Patients with a recent history (within 3 months of screening) or currently untreated B12 or folate deficiency.
• Patients with a recent history (within 3 months) or untreated clinically significant hypothyroidism or hyperthyroidism (patients with thyroid disease may be included provided they are euthyroid and stable).
• Severe aggression (=8) on item 3 of the NPI subscale, with aggression as the predominant symptom.
• Patients with psychotic DSM IV TR Axis 1 disorder other than in the context of Alzheimer’s disease, including schizophrenia, schizoaffective disorder and bipolar disorder.
• Participants known to have sensitivity to memantine, amantadine, rimantidine or lactose
• A current diagnosis of primary neurodegenerative disorders other than Alzheimer’s disease such as, Huntington’s disease, Parkinson’s disease, etc.
• Uncontrolled epilepsy.

• Current evidence of delirium.

• Moderate severe renal impairment, as measured by or equivalent to an estimated creatinine clearance of < 50 mL/min/1.73m2.

• Severe hepatic impairment

• Unable to swallow tablets or capsules.

• Low probability of treatment compliance.

• Currently taking memantine.

• Previous evidence of lack of efficacy or tolerability to memantine.

Taking any of the following substances:

• an investigational drug during the 4 weeks prior to randomization.
• a drug known to cause major organ system toxicity during the 4 weeks prior to randomization.
• started any new psychotropic 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.
• memantine during the 6 weeks prior to randomization.
• other N-methyl-D-aspartate (NMDA) antagonists: amantadine, ketamine, and dextromethorphan.
• barbiturates and primidone.
• baclofen and dantrolen.
• dextrmethorphan.
• antimuscarinics.
• anticonvulsants other than sodium valproate or carbamazepine. These 2 agents are permissible if doses have been stable for at least 4 weeks.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alzheimer's disease
MedDRA version: 9.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease

Intervention(s)

Trade Name: Ebixa
Product Name: Memantine
Pharmaceutical Form: Tablet
INN or Proposed INN: MEMANTINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-20
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Risperdal
Product Name: Risperidone
Pharmaceutical Form: Capsule*
INN or Proposed INN: RISPERIDONE
CAS Number: 106266062
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-1
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Zyprexa
Pharmaceutical Form: Capsule*
INN or Proposed INN: OLANZAPINE
CAS Number: 132539061
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-10
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Seroquel
Pharmaceutical Form: Capsule*
INN or Proposed INN: QUETIAPINE
CAS Number: 111974697
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-100
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Haloperidol (proprietary)
Pharmaceutical Form: Capsule*
INN or Proposed INN: HALOPERIDOL
CAS Number: 52868
Concentration unit: mg milligram(s)
Concentration number: 0.5-1
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: (1) to evaluate the efficacy of memantine versus neuroleptic treatment


• in preventing emergence/increase of aggression.

• in cognitive outcome.

• in preventing emergence/increase of non-aggressive agitation.

• in preventing emergence/increase of other neuropsychiatric symptoms.


(2) to evaluate the safety and tolerability of 24 weeks treatment with memantine in comparison to neuroleptics

Main Objective: The primary objective of this trial is to evaluate the efficacy of 24 weeks treatment with memantine in comparison to neuroleptics in patients with Alzheimer's disease for the maintainenance of self care.

Primary end point(s): The primary outcome is activities of daily living (Bristol ADL score). The primary analysis will utilize analysis of covariance (ANCOVA) with adjustment for baseline value of the Bristol ADL score. The primary statistical analysis will assess the performance of memantine compared to continued neuroleptic treatment for change from baseline on the primary outcomes at the 24 week assessment point by modified intention to treat, using a mixed model with imputation of uncompleted assessments.

Secondary ID(s)

Lu-11829A

68407918

Secondary Sponsor(s)

North Essex Partnership NHS Foundation Trust