Good Rate of Clinical Response to Cholinesterase Inhibitors in Alzheimer's Disease After Three Months of Treatment (NINDS-AIREN)

• ClinicalTrials.gov Identifier: NCT02007291
• Recruitment Status: Completed
• First Posted: December 10, 2013
• Results First Posted: June 12, 2018
• Last Update Posted: June 12, 2018
• Sponsor: Federal University of Minas Gerais
• Information provided by (Responsible Party): Luís Felipe José Ravic de Miranda, Federal University of Minas Gerais

Study Description

Brief Summary:

Life expectancy in Brazil has increased markedly over the last 30 years. Hence, age-related disorders, such as Alzheimer's disease (AD), warrant special attention due to their high prevalence in the elderly. Pharmacologic treatment of AD is based on cholinesterase inhibitors (ChEI) and memantine, leading to modest clinical benefits both in the short and long-term.

However, clinical response is heterogeneous and needs further investigation. Objective: To investigate the rate of response to ChEI in AD after three months of treatment. Methods: Patients with mild or moderate dementia due to probable AD or to AD associated with cerebrovascular disease were included in the study.

Condition or disease
Late Onset Alzheimer

Detailed Description:

The subjects were assessed at baseline and again after three months of ChEI treatment. Subjects were submitted to the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Katz Basic Activities of Daily Living, Pfeffer Functional Activities Questionnaire, Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Good response was defined by a gain of ≥2 points on the MMSE after three months of treatment in relation to baseline.

Study Design

• Study Type: Observational
• Actual Enrollment: 71 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Good Rate of Clinical Response to Cholinesterase Inhibitors in Mild and Moderate Alzheimer's Disease After Three Months of Treatment
• Study Start Date: June 2009
• Actual Primary Completion Date: October 2011
• Actual Study Completion Date: March 2013

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Cognitive Response After Three Months of Treatment With ChEI in Mild and Moderate Alzheimer's Disease [ Time Frame: three months ]
   Patients presented mild or moderate dementia according to the Clinical Dementia Rating (CDR). None of the individuals had been treated with Cholinesterase inhibitors (ChEI) or memantine before study entry. Donepezil, galantamine or rivastigmine were prescribed to the patients according to the clinicians' preferences. All participants were evaluated by one board certified geriatrician (LFJRM) at baseline and after 3 months of treatment, as part of an ongoing 12-month responder analysis study of ChEI in Alzheimer's Disease. The main domain examined and the evaluation tools was cognition and Mini-Mental State Examination- MMSE, respectively. MMSE scores range from 0 to 30, while the greater value is associated with a better cognition state. An increase of 2 or more points in MMSE was considered as response.

Secondary Outcome Measures :

1. Independence for Daily Activities Response After Three Months of Treatment With ChEI in Mild and Moderate Alzheimer's Disease [ Time Frame: three months ]
   Patients presented mild or moderate dementia according to the Clinical Dementia Rating (CDR). None of the individuals had been treated with Cholinesterase inhibitors (ChEI) or memantine before study entry. Donepezil, galantamine or rivastigmine were prescribed to the patients according to the clinicians' preferences. All participants were evaluated by one board certified geriatrician (LFJRM) at baseline and after 3 months of treatment, as part of an ongoing 12-month responder analysis study of ChEI in AD. The secondary domain examined was independence for daily activities and the evaluation tools used was the brazilian version of the Pfeffer Functional Activities Questionnaire (PFAQ). PFAQ scale range from 0 to 30 points and the greater value is associated with a greater dependence in daily activities.

Biospecimen Retention:   Samples With DNA

A blood sample was drawn from the patients on the first consultation for use in DNA extraction and Apolipoprotein E (APOE) genotyping. For the patients who were taking donepezil, after three, six and twelve months of treatment another blood sample were also drawn, separated in plasma and kept into the freezer at - 70 Celsius degree for further analysis of serum level of donepezil.

Eligibility Criteria

• Ages Eligible for Study: 59 Years to 93 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

A longitudinal, naturalist study, conducted at the Geriatric Outpatient Clinic of the Hospital das Clínicas at the Federal University of Minas Gerais (UFMG), in Belo Horizonte (MG), Brazil.

The sample comprised patients evaluated from June, 2009 until October, 2011.

Criteria

Inclusion Criteria:

• Patients fulfilling the National Institute on Aging and the Alzheimer's Association diagnostic criteria of probable AD dementia or the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences) diagnostic criteria of AD with cerebrovascular disease (AD + CVD)
• Patients presenting mild or moderate dementia according to the Clinical Dementia Rating (CDR), i.e., CDR 1 or 2, respectively

Exclusion Criteria:

• Patients treated with ChEI or memantine before study entry
• Patients diagnosed with frontotemporal dementia, dementia with Lewy bodies or vascular dementia,
• Patients with CDR 3
• Illiterate patients
• Patients with different comorbidities, with signs of clinical decompensation

Contacts and Locations

Sponsors and Collaborators

Federal University of Minas Gerais

Investigators

• Study Chair: Paulo Caramelli, MD, PhD; Federal University of Minas Gerais

More Information

• Responsible Party: Luís Felipe José Ravic de Miranda, Physician, Geriatrician, MD, PhD student, Federal University of Minas Gerais
• ClinicalTrials.gov Identifier: NCT02007291
• Other Study ID Numbers: 0172 / 2010
• First Posted: December 10, 2013
• Results First Posted: June 12, 2018
• Last Update Posted: June 12, 2018
• Last Verified: June 2018

Keywords provided by Luís Felipe José Ravic de Miranda, Federal University of Minas Gerais:

Alzheimer, MMSE, response, colinesterase inhibitors (ChEI)

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders