The Use of Galantamine (Reminyl ER) in Patients With MIXed Dementia: Effects on Cognition and Quality of Life

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the combination of galantamine with nimodipine in patients with mixed dementia on cognition and quality of life.

Detailed Description
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A double-blind (neither the patient nor the physician know the name of the study drug), 6-month, multicenter, placebo-controlled trial to evaluate the combination of galantamine with nimodipine in patients with mixed dementia on cognition and quality of life. The target dose of galantamine is 24 mg/day and nimodipine will be taken in fixed doses of 90 mg/day. Primary outcomes will be measured by a computerized battery of neuropsychological tests and Quality of Life (QoL) scores. Secondary outcomes will be measured by ADAS-cog, Clinical Global Impression (CGI) and Neuropsychiatric Inventory (NPI). Mixed dementia (Alzheimer's Disease (AD) associated with cerebrovascular disease) is one of the most common causes of dementia, which remain largely underdiagnosed. Little is known about specific treatments for this condition. Ischemic lesions by themselves seem to play an important role in cognitive impairment, even in the presence of AD pathology. Hypotheses: - Galantamine 16-24 mg/day in combination with nimodipine 90 mg/day is superior to galantamine monotherapy (16-24 mg/day) in improving or stabilizing cognition in patients with AD associated with cerebrovascular disease (mixed dementia), as measured by the CNTB at 6 months. - Galantamine 16-24 mg/day in combination with nimodipine 90 mg/day is superior to galantamine monotherapy (16-24 mg/day) on QoL measures in this population as measured by QoL - AD at 6 months. Group 1: galantamine oral 8mg/day for a month, 16mg/day for 4 weeks and after 24mg/day until end of study plus nimodipine oral 30mg tid during all study. Group 2: Group 1: galantamine oral 8mg/day for a month, 16mg/day for 4 weeks and after 24mg/day until end of study plus placebo oral 30mg tid during all study.

Official Title
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The Use of Galantamine (Reminyl ER) in Patients With MIXed Dementia: Effects on Cognition and Quality of Life

Conditions
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Dementia

Intervention / Treatment
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* Drug: Galantamine
* Drug: Nimodipine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients should fulfill DSM-IV criteria for dementia (APA, 1994) Patients should fulfill criteria for AD with cerebrovascular disease according to NINDS-AIREN criteria (Román et al., 1993) The severity of dementia should be mild to moderate, as defined by MMSE score between 10 and 26 (inclusive) Patients (and their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Exclusion Criteria: History of neurodegenerative disorders such as Parkinson's disease, Pick's disease or Huntington's chorea, Down's syndrome, Creutzfeldt-Jacob disease. Patients who have mild extrapyramidal signs, for which no treatment is required, are not excluded from the trial History of liver or renal insufficiency significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric, or metabolic disturbances in the past 6 months Patients who have previously received M1 agonists or cholinesterase inhibitors (tacrine, donepezil, metrifonate, rivastigmine) for treatment of Alzheimer's disease, no matter if approved or experimental can be included in this trial provided there was at least a washout period of 60 days prior to the screening assessments History of drug or alcohol abuse within the last year or prior prolonged history History of severe drug allergy or hypersensitivity including recorded hypersensitivity to cholinesterase inhibitors, choline agonists or similar agents, or bromide Subjects who have previously been enrolled in other galantamine trials.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Galantamine + Nimodipine<br> | Drug: Galantamine<br>* Galantamine 8 mg/day for one month, followed by 4 weeks of galantamine 16 mg/day. If necessary and well tolerated, dosage of galantamine will be increased to 24 mg/day.<br>Drug: Nimodipine<br>* Nimodipine 30 mg 3 times a day (tid).<br>|
| Experimental: Galantamine + Placebo<br> | Drug: Galantamine<br>* Galantamine 8 mg/day for one month, followed by 4 weeks of galantamine 16 mg/day. If necessary and well tolerated, dosage of galantamine will be increased to 24 mg/day.<br>Drug: Placebo<br>* Matching placebo three times a day (tid).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 | The Simple Reaction Time is a computerized attention test that evaluates the patient's reaction time. The number one was presented in the center of the computer screen and the patient had to press this number in the response box as quickly as possible. The reaction time, assessed 100 times per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24. The patient's finger was put over button one before the test begun. This test is part of the Computerized Neuropsychological Test Battery (CNTB). | Baseline, Week 8, Week 24 | 
| Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 | The Two-choice reaction time test is a computerized attention test in which the numbers one or five were presented in the center of the computer screen in a random order. The patient had to press the correspondent button in the response box as quickly as possible. The patient's right finger was put over the button five and the left finger over button one before the test begun. The reaction time, assessed 100 times per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24.This test is part of the Computerized Neuropsychological Test Battery (CNTB). | Baseline, Week 8, Week 24 | 
| Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 | The face recognition test is a computerized attention test in which ten unfamiliar faces were presented simultaneously on the computer screen for ten seconds to be remembered. After that, a single face was shown and the patient had to press the button one if he/she remembered or, otherwise, button five. It consisted of a random presentation of ten pre-exposed faces and ten new faces as distracters. The reaction time, assessed per patient, was averaged at each time point for each patient e.g., at baseline, Weeks 8 and 24. This test is part of the Computerized Neuropsychological Test Battery. | Baseline, Week 8, Week 24 | 
| Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 | The reaction time for word recognition and learning test is a computerized attention test that evaluates the patient's reaction time. This test is similar to the Face Recognition test procedure using Words. The recognition procedure was repeated three times to evaluate a learning effect. The reaction time, assessed per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24. This test is part of the Computerized Neuropsychological Test Battery (CNTB). | Baseline, Week 8, Week 24 | 
| The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | The Quality of Life assessment scale for caregivers of patients with Alzheimer's disease (QoL-AD) is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). It evaluates the caregivers own perceived quality of life. Total score ranges from 13 to 52. Higher scores represent a better outcome. | Baseline, Week 8, Week 24 | 
| The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | The Quality of Life assessment scale for patients with Alzheimer's disease (QoL-AD) is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). Total score ranges from 13 to 52. Higher scores represent a better outcome. | Baseline, Week 8, Week 24 | 
| The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24 | The Quality of Life assessment scale for patients with Alzheimer's disease (QoL-AD), according to the opinion of the caregiver is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). It evaluates the opinion of the caregiver about the patient's quality of life. Total score ranges from 13 to 52. Higher scores represent a better outcome. | Baseline, Week 8, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 | The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation and praxis using an 11-point Assessment Scale. It has a minimum score of 0 and a maximum severity score of 70, and a higher score indicates more impairment. | Baseline, Week 8, Week 24 | 
| The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | The Clinical Global Impression (CGI) is a scale to assess treatment response in patients with mental disorders. The Clinical Global Impression Improvement scale (CGI-I) requires the clinician to rate how much the patient's illness has improved or worsened relative to a baseline state. A patient's illness is compared to change over time and rated as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Week 4, Week 8, Week 16, Week 24 | 
| The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 | The NPI evaluates 12 neuropsychiatric domains: delusions, hallucinations, dysphoria, anxiety, aggression, euphoria, dis-inhibition, irritability/lability, apathy, aberrant motor activity, eating disorders, and night-time behavior disturbances. For present domains, the severity and frequency of the behavior are determined. Frequency is rated 1 (rarely) to 4 (very often) and Severity is scored 1 (mild) to 3 (severe). The product scores vary from 1 (mild and rarely) to 12 (very often and severe). Total scores vary from 0 (no present domain) to 144 (all domains are present, are often and severe). | Baseline, Week 8, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia, Mixed Dementia, Galantamine, Reminyl ER, Nimodipine