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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Luís Felipe José Ravic de Miranda, Federal University of Minas Gerais
ClinicalTrials.gov Identifier:
NCT02007291
First received: August 18, 2013
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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
Late Onset Alzheimer

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Federal University of Minas Gerais:

Primary Outcome Measures:
  • MMSE scores at three, six and twelve months indicate response to ChEI in mild and moderate Alzheimer's disease [ Time Frame: three, six and twelve months ] [ Designated as safety issue: No ]
    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. Clinical evaluations were performed at baseline and after three months. The domains examined and the evaluation tools were: cognition (Mini-Mental State Examination- MMSE+ Mattis Dementia Rating Scale- DRS), function (Katz - Basic Activities of Daily Living, and instrumental activities of daily living - Pfeffer Functional Activities Questionnaire - PFAQ), neuropsychiatric symptoms (Neuropsychiatric Inventory - NPI) and mood (Cornell Scale for Depression in Dementia - CSDD).


Secondary Outcome Measures:
  • Good rate of cognitive response to cholinesterase inhibitors after 3 months of treatment [ Time Frame: three, six and twelve months ] [ Designated as safety issue: No ]
    All participants were evaluated by one board certified geriatrician (LFJRM) at baseline and after three months of treatment, as part of an ongoing 12-month responder analysis study of ChEI in Alzheimer's disease. The rate of good clinical response was determined based on the proportion of patients who gained 2 or more points on the MMSE after three months of treatment in relation to baseline. Neutral response was defined by variations between -1 and +1 on the MMSE score as compared to baseline, while bad response corresponded to a decrease of 2 or more points on the MMSE after three months.


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.


Enrollment: 97
Study Start Date: June 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   59 Years to 93 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT02007291

Sponsors and Collaborators
Federal University of Minas Gerais
Investigators
Study Chair: Paulo Caramelli, MD, PhD Federal University of Minas Gerais
  More Information

No publications provided

Responsible Party: Luís Felipe José Ravic de Miranda, Physician, Geriatrician, MD, PhD student, Federal University of Minas Gerais
ClinicalTrials.gov Identifier: NCT02007291     History of Changes
Other Study ID Numbers: 0172 / 2010
Study First Received: August 18, 2013
Last Updated: December 9, 2013
Health Authority: Brazil: Ethics Committee

Keywords provided by 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
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014