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

NCT01921972 | Completed Phase 4 DMC

• 1 other identifier: Modul E.2 II
• Study Type: interventional
• Target: 232
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

Alzheimer's Disease

Keywords

AD, Dementia

Outcome Measures

Primary Outcomes (1)

• ADAScog/11

  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).

  change from Baseline to 12 months of treatment

Secondary Outcomes (7)

• ADCS-ADL

  change from Baseline to 12 months of treatment

• Clinical Dementia Rating

  change from Baseline to 12 months of treatment

• Neuropsychiatric Inventory NPI

  change from Baseline to 12 months of treatment

• Resource Utilization of Dementia Scale (RUD)

  change from Baseline to 12 months of treatment

• Burden Interview (BI)

  change from Baseline to 12 months of treatment

Study Arms (2)

Galantamine and Placebo

ACTIVE COMPARATOR

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; Drug: Placebo

Galantamine and Memantine

EXPERIMENTAL

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; Drug: Memantine

Interventions

Galantamine CR DRUG

24 mg/day with dose-titration over twelve weeks

Galantamine and Memantine; Galantamine and Placebo

Memantine DRUG

memantine 10 mg b.i.d. with a dose titration of sixteen weeks

Galantamine and Memantine

Placebo DRUG

Placebo will be similar in appearance to Memantine

Galantamine and Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or postmenopausal female outpatients.
• Age of \> 50 years at time of randomization.
• Diagnosis of probable Alzheimer's Disease (according to NINCDS-ADRDA criteria).
• Clinical and psychometric rating cut-off score (valid at randomisation): MMSE range of 15 to 26 points.
• 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).
• Patient being ambulatory having adequate vision and hearing abilities to allow neuropsychological testing.
• Patient with a knowledgeable, cooperative, reliable caregiver/informant who is willing to follow the study procedure as indicated by written informed consent.

You may not qualify if:

• Dementia of any other type than AD:
• vascular dementia
• HIS Score (modified acc. to Rosen) \> 5 or
• evidence for VD acc. to NINCDS-AIREN criteria.
• depressive pseudodementia defined acc. to DSM-IV criteria for major depression.
• other non-AD dementia.
• 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.
• 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.
• History of epileptic seizures or patient receiving antiepileptic drugs.
• 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.
• Patient who, in the opinion of the investigator, is suffering from an acute or poorly controlled illness, such as:
• Presently uncontrolled hypertension (\> 180 mmHg systolic or \> 100 mmHg diastolic).
• Myocardial infarction within the last six months.
• Patient with uncompensated congestive heart failure (NYHA Class III or IV)
• Severe renal, hepatic or gastrointestinal disease, which could alter absorption, metabolism or excretion of the trial drug.

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• German Federal Ministry of Education and Research: collaborator

Related Publications (2)

• Lim AWY, Schneider L, Loy C. Galantamine for dementia due to Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev. 2024 Nov 5;11(11):CD001747. doi: 10.1002/14651858.CD001747.pub4.

  PMID: 39498781 DERIVED

• Peters O, Fuentes M, Joachim LK, Jessen F, Luckhaus C, Kornhuber J, Pantel J, Hull M, Schmidtke K, Ruther E, Moller HJ, Kurz A, Wiltfang J, Maier W, Wiese B, Frolich L, Heuser I. Combined treatment with memantine and galantamine-CR compared with galantamine-CR only in antidementia drug naive patients with mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2015 Oct 19;1(3):198-204. doi: 10.1016/j.trci.2015.10.001. eCollection 2015 Nov.

  PMID: 29854939 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

Memantine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Isabella Heuser, Prof. Dr.

  Free University of Berlin

  STUDY DIRECTOR

• 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-Eppendorf

  PRINCIPAL INVESTIGATOR

• Christoph Mundt, Prof. Dr.

  Heidelberg University

  PRINCIPAL INVESTIGATOR

• Lutz Frölich, Prof. Dr.

  Heidelberg University

  PRINCIPAL INVESTIGATOR

• Lutz Frölich, Prof. Dr.

  Central Institute of Mental Health

  STUDY DIRECTOR

• 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.

  Technical University of Munich

  PRINCIPAL INVESTIGATOR

• Peter Falkai, Prof. Dr.

  Universitäts-Nervenklinik Homburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 14, 2013
• Study Start: November 1, 2004
• Primary Completion: November 1, 2008
• Study Completion: May 1, 2009
• Last Updated: August 14, 2013

Record last verified: 2013-08