Cognitive Changes in Alzheimer's Disease Patients Associated With or Without White Matter Changes After Rivastigmine (CAREER)

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: rivastigmine patch

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of
    • Holy Family Hospital, The Catholic Univerisy of Korea, School of Medicine
  • Busan, Korea, Republic of
    • Busan National University Hospital
  • Busan, Korea, Republic of
    • Busan Paik Hospital, Inje University College of Medicine
  • Changwon, Korea, Republic of
    • Changwon Fatima Hospital
  • Daegu, Korea, Republic of
    • Kyungpook National University School of Medicine
  • Daegu, Korea, Republic of
    • Daegu fatima hospital
  • Daegu, Korea, Republic of
    • Keimyung University School of Medicine
  • Goyang, Korea, Republic of
    • Myongji Hospital, Kwandong University College of Medicine
  • Ilsan, Korea, Republic of
    • National Health Insurance Corporation Ilsan Hospital
  • Ilsan, Korea, Republic of
    • DongGuk University International Hospital
  • Incheon, Korea, Republic of
    • Inha University College of Medicine
  • Jinju, Korea, Republic of
    • Gyeongsang National University College of Medicine
  • Kwangju, Korea, Republic of
    • Chonnam National University, Medical School
  • Seongnam, Korea, Republic of
    • Seoul National Unviersity College of Medicine, Clinical neuroscience center, Seoul National Unviersity Bundang Hospital
  • Seoul, Korea, Republic of
    • The Catholic Univerisy of Korea, School of Medicine
  • Yangsan, Korea, Republic of
    • Pusan National University Yangsan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: without white matter change	Drug: rivastigmine patch; rivastigmine patch 5cm2 for 4 weeks and then augmented to 10cm2 for 20 weeks; Other Names: Exelon patch
Active Comparator: with white matter change group	Drug: rivastigmine patch; rivastigmine patch 5cm2 for 4 weeks and then augmented to 10cm2 for 20 weeks; Other Names: Exelon patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The changes of cognitive function as measured by ADAS-Cog	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	24 weeks
MMSE (Mini-Mental State Examination)	24 weeks
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)	24 weeks
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)	24 weeks
Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI)	24 weeks
Caregiver burden scale	24 weeks

Collaborators and Investigators

• Sponsor: Dong-A University
• Collaborators: Novartis Korea Ltd.
• Investigators: Principal Investigator: Kyung Won Park, MD, PhD, Dong-A University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2011
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: June 21, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): February 5, 2018
• Last Update Submitted That Met QC Criteria: February 2, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Alzheimer's disease; rivastigmine patch; white matter change
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Cholinesterase Inhibitors; Rivastigmine
• Other Study ID Numbers: NeuroPark