The Predictive Factors of Good Clinical Response to Cholinesterase Inhibitors in Alzheimer Disease and Mixed Dementia

NCT02187276 | Completed DMC

• 1 other identifier: 0172/2010
• Study Type: observational
• Target: 129
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background and objectives: The aims of this naturalistic study were: to analyze factors which could be predictive of good response to cholinesterase inhibitors (ChEI), such as: age, sex, schooling, mild (CDR 1) or moderate Alzheimer's disease (AD),(CDR 2), Apoliprotein epsilon 4 (APOE Ɛ4), among others, in their cognitive and clinical response. We also classified patients according to their response to Mini mental State of Examination (MMSE). Finally we saw the polymorphisms of APO E and cytochrome P450 2D6 (CYP2D6) and tried to correlate the response with different allelic forms of Apo E and among others with wild type homozygotes (wt/wt) and their polymorphisms (CYP2D6\*3,\*4, \*5, \*6 and 10) of CYP 2D6. Patients and Methods: 129 patients were diagnosed as AD or AD+cerebrovascular disease (CVD) mild or moderate. After 12 month-treatment, 97 patients completed the study. They were assessed (four) times. In the first visit, without taking ChEI, after 3, 6 and 12 month-treatment, they were taking donepezil or rivastigmine or galantamine. We also extracted 5 mL of blood sample to genotype the DNA. In each visit, we applied cognitive, functional, mood and behavior scales. Good responders were defined as those who scored \> 2 in MMSE. Results and Conclusion: In longitudinal analysis, patients with mild AD and good responders at 3 months were considered good responders at 12 months. We obtained a higher rate of good responders comparing with other researches (27.8%). There was no correlation between dose, APOE and CYP 2D6 polymorphisms, although we already obtained clinical results with the dose dosage of 5mg.

Conditions

Alzheimer Disease, Late Onset

Keywords

Predictive factors of response; mild and moderate; Alzheimer disease; mixed dementia; APOE; polymorphisms of CYP 2D6

Outcome Measures

Primary Outcomes (1)

• Cognitive results

  Clinical assessment: The clinical domains examined and the respective evaluation tools were: global cognition - MMSE, clock drawing test score and Mattis Dementia Rating Scale - DRS). Patients were seen between 06/2009 to 03/2013. Good clinical responders were those who scored ≥ 2 on the MMSE after 12 month-treatment, the neutrals had the scores between -1 and +1, and bad responders scored ≤ -2 at the same period. A subgroup who scored \> 2 on the MMSE were defined as very good responders. Patients were seen for four times: at the first consultation (n=129), at three (n=114), six (n=105) and twelve months of treatment (n=97).

  Patients were evaluated from 06/2009 to 03/2013 for four times - first visit ( without taking medication), after three, six and 12 months of treatment with cholinesterase inhibitors (up to 12 months)

Secondary Outcomes (1)

• Genetic and biochemical analyzes

  To correlate allelic forms of APOE and CYP 2D6 polymorphisms with the response (up to 12 months)

Other Outcomes (1)

• Determination of the concentration of donepezil

  After 12 months-treatment the concentration of donepezil was measured

Study Arms (1)

Alzheimer disease or mixed dementia

Patients were evaluated four times. In the first consultation, without taking cholinesterase inhibitors (ChEI), after three, six and 12 months taking ChEI.

Drug: cholinesterase inhibitors

Interventions

cholinesterase inhibitors DRUG

The first group received donepezil (5 or 10 mg) the second group received galantamine (16 or 24 mg) The third group received rivastigmine (3 or 4,5 or 6 mg BID) according to the treating physician.

Also known as: No applicable

Alzheimer disease or mixed dementia

Eligibility Criteria

• Age: 59 Years - 92 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Eligible patients were those who spontaneously went to the outpatient units to be diagnosed and presented cognitive, functional, and in many cases, behavioral symptoms.

You may qualify if:

• \- AD diagnosis or AD with CVD according the criteria of National Institute on Aging and the Alzheimer's Association workgroup and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)

You may not qualify if:

• Patients with mild cognitive impairment;
• Other types of dementia, such as pure vascular dementia, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration;
• Severe dementia (CDR 3)
• Those who were already taking ChEI,
• If there have not been agreement between the first researcher and the treating physician.

Sponsors & Collaborators

• Federal University of Minas Gerais: lead

Biospecimen

Retention: SAMPLES WITH DNA

Genetic and biochemical analyzes A blood sample (5 mL) was withdrawn from all patients on the first consultation for DNA extraction and APOE genotyping in its different allelic forms (Ɛ2, Ɛ3, Ɛ4). An additional blood sample (10 mL) was withdrawn from patients who took donepezil (51 patients) and was kept in a tube with heparin and frozen at - 70 ° C. In this group of patients, we genotyped the APOE and assessed the polymorphism of CYP 2D6 (\*3,\*4,\*5,\*6 and\*10). This procedure was done when they came at 3, 6 and 12 months consultation, respectively.

MeSH Terms

Conditions

Alzheimer Disease; Lymphoma, Follicular; Mixed Dementias

Interventions

Cholinesterase Inhibitors

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs

Study Officials

• Paulo Caramelli, Profesor

  Federal University of Minas Gerais

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician, Geriatrician, PhD Student

Study Record Dates

• First Submitted: July 5, 2014
• First Posted: July 11, 2014
• Study Start: June 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: September 12, 2014

Record last verified: 2014-09