The Efficacy of a Combination Regimen in Patients With Mild to Moderate Probable Alzheimer's Disease (AD-Combi)
|ClinicalTrials.gov Identifier: NCT01921972|
Recruitment Status : Completed
First Posted : August 14, 2013
Last Update Posted : August 14, 2013
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease||Drug: Galantamine CR Drug: Memantine Drug: Placebo||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||232 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Competence Network - Dementia (BMBF) "Pharmacological and Psychosocial Treatment" (Modul E.2) Part II: The Efficacy of a Combination Regimen in Patients With Mild to Moderate Probable Alzheimer's Disease|
|Study Start Date :||November 2004|
|Actual Primary Completion Date :||November 2008|
|Actual Study Completion Date :||May 2009|
Active Comparator: Galantamine and Placebo
Subjects in this group will receive 4 weeks of 8 mg/day galantamine CR, followed by 4 weeks of 16 mg/day and from week 9 up to the end of the trial of 24 mg/day.
Drug: Galantamine CR
24 mg/day with dose-titration over twelve weeks
Placebo will be similar in appearance to Memantine
Experimental: Galantamine and Memantine
Galantamine titration will be performed as described above. Memantine titration will be performed over 4 weeks in steps of 5 mg/day up to 20mg/day (10 mg b.i.d.). 50 % of this group will receive galantamine first, 50 % of the group will receive memantine first to allow for differential qualitative evaluation of tolerability of a combination therapy.
Drug: Galantamine CR
24 mg/day with dose-titration over twelve weeks
memantine 10 mg b.i.d. with a dose titration of sixteen weeks
- ADAScog/11 [ Time Frame: change from Baseline to 12 months of treatment ]Alzheimer's Disease Assessment Scale (ADAS-cog/11) The ADAS consists of two parts - a cognitive subscale and a behavioral subscale. The behavioural subscale will not be used in this trial. The cognitive subscale, the ADAS-cog/11, consisting of Word Recall and Word Recognition memory tests, Object and Finger Naming, Commands, Constructional Praxis, Ideational Praxis, Orientation, Remembering Test Instructions, Spoken Language Ability, Comprehension of Spoken Language and Word Finding Difficulty will be the primary variable in this trial. In this trial the German version of the ADAS-cog/11 will be employed (Ihl & Weyer, 1993).
- ADCS-ADL [ Time Frame: change from Baseline to 12 months of treatment ]The ability to perform activities of daily living will be assessed using the AD version of the Alzheimer's Disease Cooperative Study ADL inventory (Galasko et al., 1997, 2004). This instrument comprises questions about 23 basic and instrumental ADLs. For each ADL, the scores range from 0 (non-performance of the activity or the need for extensive help) to the highest score (representing independent performance of the activity). The total score ranges from 0 (no function) to 78 (maximal function).
- Clinical Dementia Rating [ Time Frame: change from Baseline to 12 months of treatment ]The CDR Scale is a clinician-rated dementia staging system that tracks the progression of cognitive and functional deterioration. Scores are on a scale of 0 - 5, with 0 = no dementia, 0.5 = questionable dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia, 4 = profound dementia, and 5 = terminal dementia. Cognitive and functional abilities that are assessed are memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care. Memory is considered the primary driver for scoring with the other categories secondary.
- Neuropsychiatric Inventory NPI [ Time Frame: change from Baseline to 12 months of treatment ]The Neuropsychiatric Inventory (Cummings et al., 1994) is used to assess 10 areas of non-cognitive symptoms which are common in dementia, including delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time. Interrater reliability and test-retest reliability are acceptable.
- Resource Utilization of Dementia Scale (RUD) [ Time Frame: change from Baseline to 12 months of treatment ]For each patient, use of medical and social services will be determined using the Resource Utilization of Dementia Scale (Wimo et al., 1998). This instrument is used to rate the primary caregiver (time spent on caring, occupational status, use of medical and social services, use of medications) and the patient (living arrangement, nursing home and hospital admissions, use of medical and social services) to estimate healthcare cost
- Burden Interview (BI) [ Time Frame: change from Baseline to 12 months of treatment ]
The Burden Interview (Zarit & Zarit, 1983, 1990) has been designed to assess the stress experienced by family caregivers of elderly and disabled persons. It can be completed by caregivers themselves or as part of an interview. Caregivers are asked to respond to a series of 22 items about the impact of the patient's disabilities on their life. For each item caregivers are to indicate how often they have felt that way: never, rarely, sometimes, quite frequently, or nearly always.
The Burden Interview is scored by summing the responses of the individual items. The total score ranges from 0 to 88. Higher scores indicate greater caregiver distress.
- Adverse Event Reports [ Time Frame: 12 months of treatment ]
- Rate of brain atrophy [ Time Frame: change from baseline to 12 months of treatment ]Serial volumetric MRI will generate data-sets used for whole brain rate of atrophy determinations, hippocampal rate of atrophy measurements as well as MR-spectroscopic parameters
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01921972
|Study Director:||Isabella Heuser, Prof. Dr.||Free University of Berlin|
|Principal Investigator:||Wolfgang Maier, Prof. Dr.||University of Bonn|
|Principal Investigator:||Wolfgang Gaebel, Prof. Dr.||Heinrich-Heine University, Duesseldorf|
|Principal Investigator:||Johannes Kornhuber, Prof. Dr.||University of Erlangen-Nürnberg|
|Principal Investigator:||Konrad Maurer, Prof. Dr.||University of Frankfurt|
|Principal Investigator:||C H Lücking, Prof. Dr.||University of Freiburg|
|Principal Investigator:||Eckhart Rüther, Prof. Dr.||University of Göttingen|
|Principal Investigator:||Mathias Berger, Prof. Dr.||University of Freiburg|
|Principal Investigator:||Dieter Naber, Prof. Dr.||University of Hamburg|
|Principal Investigator:||Christoph Mundt, Prof. Dr.||Heidelberg University|
|Principal Investigator:||Lutz Frölich, Prof. Dr.||Heidelberg University|
|Study Director:||Lutz Frölich, Prof. Dr.||Central Institute of Mental Health|
|Principal Investigator:||Fritz A Henn, Prof. Dr.||Central Institute of Mental Health|
|Principal Investigator:||Matthias C Angermeyer, Prof. Dr.||LMU München|
|Principal Investigator:||Hans Förstl, Prof. Dr.||Technische Universität München|
|Principal Investigator:||Peter Falkai, Prof. Dr.||Universitäts-Nervenklinik Homburg|