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

• ClinicalTrials.gov Identifier: NCT00814658
• Recruitment Status: Completed
• First Posted: December 25, 2008
• Results First Posted: August 26, 2013
• Last Update Posted: August 26, 2013
• Sponsor: Janssen-Cilag Farmaceutica Ltda.
• Information provided by (Responsible Party): Janssen-Cilag Farmaceutica Ltda.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Dementia	Drug: Galantamine; Drug: Nimodipine; Drug: Placebo	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Use of Galantamine (Reminyl ER) in Patients With MIXed Dementia: Effects on Cognition and Quality of Life
• Study Start Date: June 2008
• Actual Primary Completion Date: October 2009
• Actual Study Completion Date: October 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Galantamine + Nimodipine	Drug: Galantamine; 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.; Drug: Nimodipine; Nimodipine 30 mg 3 times a day (tid).
Experimental: Galantamine + Placebo	Drug: Galantamine; 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.; Drug: Placebo; Matching placebo three times a day (tid).

Outcome Measures

Primary Outcome Measures :

1. Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 [ Time Frame: Baseline, Week 8, 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).
2. Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 [ Time Frame: Baseline, Week 8, 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).
3. Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 [ Time Frame: Baseline, Week 8, 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.
4. Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 [ Time Frame: Baseline, Week 8, 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).
5. The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 [ Time Frame: 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.
6. The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 [ Time Frame: 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.
7. 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 [ Time Frame: 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.

Secondary Outcome Measures :

1. The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 [ Time Frame: Baseline, Week 8, 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.
2. The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 [ Time Frame: Week 4, Week 8, Week 16, 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.
3. The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 [ Time Frame: Baseline, Week 8, 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).

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Sponsors and Collaborators

Janssen-Cilag Farmaceutica Ltda.

Investigators

• Study Director: Janssen-Cilag Farmaceutica Ltda. Clinical Trial; Janssen-Cilag Farmaceutica Ltda.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Caramelli P, Laks J, Palmini AL, Nitrini R, Chaves ML, Forlenza OV, Vale Fde A, Barbosa MT, Bottino CM, Machado JC, Charchat-Fichman H, Lawson FL. Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study). Arq Neuropsiquiatr. 2014 Jun;72(6):411-7.

• Responsible Party: Janssen-Cilag Farmaceutica Ltda.
• ClinicalTrials.gov Identifier: NCT00814658
• Other Study ID Numbers: CR014938; GALDEM4008 ( Other Identifier: Janssen-Cilag Farmaceutica Ltda. )
• First Posted: December 25, 2008
• Results First Posted: August 26, 2013
• Last Update Posted: August 26, 2013
• Last Verified: August 2013

Keywords provided by Janssen-Cilag Farmaceutica Ltda.:

Dementia; Mixed Dementia; Galantamine; Reminyl ER; Nimodipine

Additional relevant MeSH terms:

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Nimodipine; Galantamine; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Parasympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Nootropic Agents; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Vasodilator Agents