The Efficacy of a Combination Regimen in Patients With Mild to Moderate Probable Alzheimer's Disease

• Status: Completed
• Trial end date: 2009-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a national multicenter, double-blind, randomized, parallel-group trial of 12 months in duration. Following a 4 week wash-out period, subjects will be randomized to one of 2 treatment groups: (1) galantamine CR 24 mg/day with dose-titration over twelve weeks[maintenance phase from week 9], (2) a combination of galantamine CR 24 mg/day plus memantine 10 mg b.i.d. with a dose titration of sixteen weeks (12 weeks for galantamine [maintenance phase from week 9], additional 4 weeks for memantine).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Charite University, Berlin, Germany
• Collaborator: German Federal Ministry of Education and Research
• Treatments: Galantamine; Memantine

Criteria

Inclusion Criteria:

1. Willingness to participate, as indicated by written informed consent of the patient. The competence of the participating patient has to be assessed by a physician who is not involved in this trial.

2. Male or postmenopausal female outpatients.

3. Age of > 50 years at time of randomization.

4. Diagnosis of probable Alzheimer's Disease (according to NINCDS-ADRDA criteria).

5. Clinical and psychometric rating cut-off score (valid at randomisation): MMSE range of 15 to 26 points.

6. MRI brain scan not older than 12 months (before randomization) compatible with the diagnosis of Alzheimer's Disease. (The MRI brain scan must be repeated if older than 12 months or if clinically indicated).

7. Patient being ambulatory having adequate vision and hearing abilities to allow neuropsychological testing.

8. Patient with a knowledgeable, cooperative, reliable caregiver/informant who is willing to follow the study procedure as indicated by written informed consent.

Exclusion Criteria:

1. Dementia of any other type than AD:

1. vascular dementia

• HIS Score (modified acc. to Rosen) > 5 or

• evidence for VD acc. to NINCDS-AIREN criteria.

2. depressive pseudodementia defined acc. to DSM-IV criteria for major depression.

3. other non-AD dementia.

2. Significant neurological disease other than AD, such as cerebral tumor, Huntington's disease, Parkinson's disease, normal pressure hydrocephalus, subdural hematoma, mental retardation, history of brain surgery or serious head trauma with residual deficits.

3. Diagnosis of psychosis (requiring hospitalization or antipsychotic therapy for more than two weeks) within the past 10 years not associated with AD or a diagnosis of alcoholism or drug dependence within the past 10 years.

4. History of epileptic seizures or patient receiving antiepileptic drugs.

5. Abnormal laboratory test results considered clinically relevant for dementia: e.g., electrolyte changes, folate deficiency, vitamin B12 deficiency, pathological thyroid function (T3 and TSH levels), positive syphilis serology.

6. Patient who, in the opinion of the investigator, is suffering from an acute or poorly controlled illness, such as:

1. Presently uncontrolled hypertension (> 180 mmHg systolic or > 100 mmHg diastolic).

2. Myocardial infarction within the last six months.

3. Patient with uncompensated congestive heart failure (NYHA Class III or IV)

4. Severe renal, hepatic or gastrointestinal disease, which could alter absorption, metabolism or excretion of the trial drug.

5. Serum creatinine > 130 μmol/l or 1.5 mg/dl, transaminases (ALAT, ASAT) or GGT > twice the upper limit of normal range.

6. Uncontrolled diabetes on entry into the double-blind phase of the research project (fasting blood glucose > 10.0 mmol/l or 180 mg/dl in repeated tests) or patient requiring insulin treatment.

7. Patient taking any inadmissible medication, such as:

• Any investigational drug.

• Anticonvulsants (incl. barbiturates).

• Anti-Parkinson agents.

• Dopaminergic agents.

• Amantadine.

• Antimuscarinic agents (i. e., anticholinergics).

• Selegiline, MAOI.

8. Any condition that precludes cooperation with the tests or other investigations during the study (e.g., seeing or hearing loss, relevant confusion or agitation, musculoskeletal disorders, contraindication for magnetic resonance imaging, i.e., presence of pacemaker, metallic implants in high risk areas, presence of metallic material in high risk areas, history of claustrophobia. Hip implants are not contraindicated).

9. Patient has participated in an investigational clinical trial during the last 2 months.