Memantine and Antipsychotics Use (MemAP)

• ClinicalTrials.gov Identifier: NCT00649220
• Recruitment Status: Terminated
• First Posted: April 1, 2008
• Results First Posted: September 13, 2011
• Last Update Posted: September 26, 2011
• Sponsor: Merz Pharmaceuticals GmbH
• Information provided by (Responsible Party): Merz Pharmaceuticals GmbH

Study Description

Brief Summary:

To investigate the potential to reduce concomitant antipsychotic medication use in subjects with moderate dementia of Alzheimer's type, treated with memantine.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: Memantine	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective, Single-arm, Multi-centre, Open-label Study to Investigate the Potential to Reduce Concomitant Antipsychotics Use in Patients With Moderate to Severe Dementia of Alzheimer's Type (DAT) Treated With Memantine
• Study Start Date: July 2008
• Actual Primary Completion Date: May 2009
• Actual Study Completion Date: June 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Memantine	Drug: Memantine; memantine tablets, twice a day (bid), for 20 weeks

Outcome Measures

Primary Outcome Measures :

1. Maximum Dose Reduction of Antipsychotics (AP) in Percent of Defined Daily Dose (DDD) From Baseline to a Post-baseline Visit at Which the Value of the Visual Analogue Scale (VAS) Compared With the Baseline Value Was =< 15 Percent. [ Time Frame: Week 8-20 post baseline ]
   VAS: see #8. Mean "percent of the total Defined Daily Dose (DDD)", averaged over one week, was calculated. Total DDD was calculated as sum of DDD for each AP drug. DDD is the assumed average maintenance dose per day defined by WHO. The reduction of AP Δ [percent] was calculated as a difference between the mean total DDD recorded at baseline and the mean total DDD recorded at the respective week. Measurements from those post-baseline visits were taken into account only when the value of the VAS was not substantially worse compared to baseline.

Secondary Outcome Measures :

1. Reduction of Antipsychotic Drug Dose From Baseline to Week 8, 12, 16 and/or 20. [ Time Frame: Week 8-20 post Baseline ]
   See #1 and #8. Change of <0 reveals a reduction of AP compared to baseline.
2. Change in the Mini-Mental State Examination (MMSE) Score Value From Baseline to Week 20. [ Time Frame: Week 20 post baseline ]
   MMSE is a brief, physician-administered scale, designed for measuring the cognitive functions, such as: orientation, memory, attention, naming, and comprehension. The scoring range of MMSE is 0 to 30 points. A score of 23 or lower is indicative of cognitive impairment. Change of >0 reveals an improvement compared to baseline.
3. Change of "Test for the Early Detection of Dementia With Discrimination From Depression [TE4D]" Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - First Part: Total Dementia [ Time Frame: Week 4-20 post baseline ]

   TE4D is a psychometric, physician-administered test that is used for both screening subjects with early dementia and monitoring the clinical progress of the disease. The first part consists of 9 items, which assess different symptoms associated with dementia such as memory, time-orientation, etc. The scoring range is 0 to 50 points. A score of 35 or lower is an indication of dementia.

   A change >0 represents an improvement.

4. Change of "Test for the Early Detection of Dementia With Discrimination From Depression [TE4D]" Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - Second Part: Total Depression [ Time Frame: Week 4-20 post Baseline ]

   TE4D is a psychometric, physician-administered test that is used for both screening subjects with early dementia and monitoring the clinical progress of the disease. The second part consists of a proxy rating and a self-assessment rating. The scoring range of each rating is 1 to 10. The maximum total score of 10 corresponds to severe depression.

   A change <0 reveals an improvement compared to baseline.

5. Change of Modified Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADLB19) Score Value From Baseline to Week 4, 8, 12, 16, and/or 20. [ Time Frame: Week 4-20 post Baseline ]

   The modified ADCS-ADL19 is comprehensive battery of ADL questions aimed to measure the functional ability of subjects with Dementia of Alzheimer's type over a broad range of dementia severity. It has a scoring range of 0 to 54 with the lower scores indicating greater functional impairment. Each ADL item was rated from the highest level of independent performance to complete loss.

   Change of >0 reveals an improvement compared to baseline.

6. Change of Nurses' Observation Scale for Geriatric Patients [NOSGER] Total Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 [ Time Frame: Week 4-20 post Baseline ]

   NOSGER is a comprehensive scale, which contains 30 items of behavior, each rated on a 5-point scale according to the frequency of occurrence by direct observation. Item scores are summarized into 6 dimension scores: memory, instrumental activities of daily life, self-care, mood, social behavior, and disturbing behavior. The NOSGER has a scoring range of 30 to 150 with the higher scores indicating worse subject's status. The items in each group are rated for their frequency ranging from 1 (never) to 5 (always).

   A change of <0 reveals an improvement compared to baseline.

7. Change in the VAS Score From Baseline to Week 8, 12, 16 and/or 20. [ Time Frame: Week 8-20 post Baseline ]
   VAS is a report device to measure the subject's burden caused by behavioral symptoms. To measure the burden on the VAS only the first 3 items of the Neuropsychiatric Inventory (NPI) Questionnaire were considered (delusions, hallucinations (visual and auditory), and agitation / aggression). The VAS consists of a 100 mm horizontal line, anchored at the ends with the reference "not at all" and "extremely". The VAS score was determined by measuring in mm from the left hand end of the line to the point, where the investigator had marked the magnitude of a subject's burden.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Current diagnosis of probable Alzheimer's disease consistent with NINCDS-ADRDA criteria or with DSM IV TR criteria for Dementia of the Alzheimer's type.
• MRI or CT scan supporting the diagnosis of DAT without indications of any relevant other CNS disorders.
• Patients treated with any acetylcholinesterase inhibitor (AChEI) man be included.
• The patient should have German as a mother-tongue or at least speak the language fluently.

Exclusion criteria:

• Evidence (including CT/MRI results) of any clinically significant central nervous system disease other than Alzheimer's disease.
• Modified Hachinski Ischemia score greater than 4 at screening.
• Intake of any medication that is contra-indicated in combination with memantine.
• Treatment with depot antipsychotics.
• History of severe drug allergy, or hypersensitivity, or patients with known hypersensitivity to memantine, amantadine or lactose.
• Known or suspected history of alcoholism or drug abuse within the past 10 years.
• Previous treatment with memantine or participation in an investigational study with memantine.

Contacts and Locations

Locations

Germany

Alexianer Hospital

Krefeld, North-Rhine-Westphalia, Germany

Sponsors and Collaborators

Merz Pharmaceuticals GmbH

Investigators

• Study Director: Medical Expert; Merz Pharmaceuticals GmbH

More Information

• Responsible Party: Merz Pharmaceuticals GmbH
• ClinicalTrials.gov Identifier: NCT00649220
• Other Study ID Numbers: MRZ 90001-0716/1; 2007-004489-41 ( EudraCT Number )
• First Posted: April 1, 2008
• Results First Posted: September 13, 2011
• Last Update Posted: September 26, 2011
• Last Verified: September 2011

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Memantine; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents