Clinical trial NCT01380288: Cognitive Changes in Alzheimer's Disease Patients Associated With or Without White Matter Changes After Rivastigmine
Official title: Changes of Cognitive Function in Patients With Mild to Moderate Alzheimer's Disease Associated With or Without White Matter Changes After Rivastigmine Patch Therapy - Multi-center, Prospective, Open-label Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
rivastigmine patch
white matter change
Lead sponsor: Dong-A University
Sponsor class: OTHER
Collaborators: name: Novartis Korea Ltd.
First posted: 2011-06-27
Enrollment: 300
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate and compare the changes of cognitive function (as measured by ADAS-Cog) in the two group of patients with Alzheimer's disease (AD) associated with and without white matter changes after rivastigmine patch therapy.

Detailed description: Acetylcholinesterase inhibitors (AChEIs) increase the amount acetylcholine at ACh receptors within the brain, and are the primary medications used to treat AD. Alzheimer's disease patients are frequently associated with mild or moderate white matter changes on MR imaging. The impact of whiter matter changes on the efficacy of cognition, functional abilities, behavioral and psychiatric symptoms and caregiver burden for probable Alzheimer's disease is not well known. There are very few studies for the efficacy of rivastigmine between the patients with mild to moderate Alzheimer's disease associated with or without vascular risk factors.

Recently, the rivastigmine patch demonstrated efficacy comparable to the highest doses of rivastigmine capsules, with markedly improved tolerability profile. The investigators hypothesized that rivastigmine patch will provide benefits to AD patients with white matter changes compared to those without any white matter changes. Possible explanation about favorable benefits for AD with white matter changes is that rivastigmine may act on both Alzheimer's and vascular pathologies contributing to dementia, providing additive treatment effects in patients suffering from both conditions concurrently. To our Knowledge, there was no study or clinical trial to compare the changes of cognitive function, ADL, BPSD and caregiver burden in two groups of patient with Alzheimer's disease associated with or without white matter changes after rivastigmine transdermal patch therapy.

Eligibility criteria: Inclusion Criteria:

* AD in NINCDS-ADRDA criteria, mild to moderate
* probable AD with or without mild to moderate whiter matter lesions, excluding multiple large vessel infarcts or a single, strategically placed infarct (angular gyrus, thalamus, basal forebrain, territory of the posterior or anterior cerebral artery) on MRI scan (within 12 months)
* MMSE score : 10 to 26 at screening
* Hachinski scores ≤ 4
* No clinically significant laboratory abnormalities, such as thyroid disease, vitamine B12 deficiency or folic acid deficiency

Exclusion Criteria:

* Current evidence of history of neurological, psychiatric and other illness that could contribute to dementia
* Subjects with clinical significant cardiovascular disease, stroke, pulmonary disease or any other medical disease in the past 6 months
* History of cancer within the last 5 years
* Subjects with evidence or history of clinically significant allergic reaction to AchEI or drugs
* Subjects who had significant visual or hearing difficulties

Primary outcomes:
measure: The changes of cognitive function as measured by ADAS-Cog
timeFrame: 24 weeks
Secondary outcomes:
measure: MMSE (Mini-Mental State Examination)
timeFrame: 24 weeks
measure: Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)
timeFrame: 24 weeks
measure: Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
timeFrame: 24 weeks
measure: Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI)
timeFrame: 24 weeks
measure: Caregiver burden scale
timeFrame: 24 weeks
measure: Adverse events
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Bucheon
country: Korea, Republic of
facility: Holy Family Hospital, The Catholic Univerisy of Korea, School of Medicine
city: Busan
country: Korea, Republic of
facility: Busan National University Hospital
city: Busan
country: Korea, Republic of
facility: Busan Paik Hospital, Inje University College of Medicine
city: Changwon
country: Korea, Republic of
facility: Changwon Fatima Hospital
city: Daegu
country: Korea, Republic of
facility: Daegu Fatima Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University School of Medicine
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University School of Medicine
city: Goyang
country: Korea, Republic of
facility: Myongji Hospital, Kwandong University College of Medicine
city: Ilsan
country: Korea, Republic of
facility: Dongguk University International Hospital
city: Ilsan
country: Korea, Republic of
facility: National Health Insurance Corporation Ilsan Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University College of Medicine
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University College of Medicine
city: Kwangju
country: Korea, Republic of
facility: Chonnam National University, Medical School
city: Seongnam
country: Korea, Republic of
facility: Seoul National Unviersity College of Medicine, Clinical neuroscience center, Seoul National Unviersity Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic Univerisy of Korea, School of Medicine
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
affiliation: Dong-A University
name: Kyung Won Park, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Park KW, Kim EJ, Han HJ, Shim YS, Kwon JC, Ku BD, Park KH, Yi HA, Kim KK, Yang DW, Lee HW, Kang H, Kwon OD, Kim S, Lee JH, Chung EJ, Park SW, Park MY, Yoon B, Kim BC, Seo SW, Choi SH. Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial. PLoS One. 2017 Aug 7;12(8):e0182123. doi: 10.1371/journal.pone.0182123. eCollection 2017.