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

• Sponsor: Federal University of Minas Gerais (Other)
• Overall Status: Completed
• CT.gov ID: NCT02007291
• Collaborator: (none)
• Enrollment: 71
• Duration (Months): 45

Study Details

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	Intervention/Treatment	Phase
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: Jun 1, 2009
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Mar 1, 2013

Outcome Measures

Primary Outcome Measures

1. Cognitive Response After Three Months of Treatment With ChEI in Mild and Moderate Alzheimer's Disease [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 59 Years to 93 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

No locations specified.

Sponsors and Collaborators

• Federal University of Minas Gerais

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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: Dec 10, 2013
• Last Update Posted: Jun 12, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Luís Felipe José Ravic de Miranda, Physician, Geriatrician, MD, PhD student, Federal University of Minas Gerais: Alzheimer, MMSE, response, colinesterase inhibitors (ChEI)
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Arm/Group Title	CDR1 Patients Taking Cholinesterase Inhibitors	CDR2 Patients Taking Cholinesterase Inhibitors
Arm/Group Description	The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.	The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.
Period Title: Overall Study
STARTED	48	23
COMPLETED	48	23
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Patients Taking Cholinesterase Inhibitors
Arm/Group Description	The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.
Overall Participants	71
Age, Customized (Count of Participants)
≤ 69 years old	12 16.9%
70-79 years old	36 50.7%
≥ 80 years old	23 32.4%
Sex: Female, Male (Count of Participants)
Female	45 63.4%
Male	26 36.6%
Region of Enrollment (Count of Participants)
Brazil	71 100%

Outcome Measures

1. Primary Outcome

Title	Cognitive Response After Three Months of Treatment With ChEI in Mild and Moderate Alzheimer's Disease
Description	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.
Time Frame	three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CDR 1 Patients Taking Cholinesterase Inhibitors	CDR 2 Patients Taking Cholinesterase Inhibitors
Arm/Group Description	The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.	The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.
Measure Participants	43	28
MMSE- baseline	19 (4.3)	11.3 (2.4)
MMSE - 3 months	18.9 (4.5)	11.5 (2.8)

2. Secondary Outcome

Title	Independence for Daily Activities Response After Three Months of Treatment With ChEI in Mild and Moderate Alzheimer's Disease
Description	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.
Time Frame	three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CDR 1 Patients Taking Cholinesterase Inhibitors	CDR 2 Patients Taking Cholinesterase Inhibitors
Arm/Group Description	The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.	The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.
Measure Participants	43	28
PFAQ - baseline	14.9 (8.8)	26.9 (4.1)
PFAQ - 3 months	16.2 (8.8)	27.1 (3.5)

Adverse Events

Time Frame	3 months.
Arm/Group Title	CDR1 Patients Taking Cholinesterase Inhibitors		CDR2 Patients Taking Cholinesterase Inhibitors
Arm/Group Description	The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.		The sample comprised patients evaluated from June, 2009 until October, 2011.During this period, 71 patients were evaluated at baseline and after 3 month-treatment. Donepezil, rivastigmine or galantamine were prescribed to the patients according to the clinicians' preferences. The target dosages considered for treatment effect evaluation were 5 to 10 mg for donepezil, 16 to 24 mg for galantamine and 6 to 12 mg for rivastigmine. The first investigator (LFJRM) did not have any influence on the prescription.
All Cause Mortality
	CDR1 Patients Taking Cholinesterase Inhibitors		CDR2 Patients Taking Cholinesterase Inhibitors
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CDR1 Patients Taking Cholinesterase Inhibitors		CDR2 Patients Taking Cholinesterase Inhibitors
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	CDR1 Patients Taking Cholinesterase Inhibitors		CDR2 Patients Taking Cholinesterase Inhibitors
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.