Donepezil in the Prevention of Post-Operative Cognitive Decline - Full Text View

Sponsored by:	Pfizer
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00182845

Purpose

The purpose of this study is to evaluate the feasibility of using Donepezil to prevent post-operative cognitive decline (POCD) among individuals aged 65 and older who have a baseline mild cognitive impairment (MCI) and are undergoing elective hip or knee replacement.

Condition	Intervention	Phase
Postoperative Complications Delirium	Drug: Donepezil	Phase IV

Drug Information available for: Donepezil E 2020

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Preventing Post-Operative Cognitive Decline

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:

Changes in the International Study of Post-Operative Cognitive Decline (ISPOCD) and the CogHealth computerized battery tests at 1 week and 12 weeks after surgery

Secondary Outcome Measures:

Delirium status measured by the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale (MDAS) daily during the post-operative period
Global cognitive status assessed using the Mini Mental Status Exam (MMSE)
Length of stay in the hospital post-operatively
Discharge site
Adverse effects

Estimated Enrollment:	30
Study Start Date:	February 2005
Study Completion Date:	April 2007
Primary Completion Date:	April 2007 (Final data collection date for primary outcome measure)

Detailed Description:

Up to 65% of elderly patients undergoing hip or knee surgery suffer from declining brain function known as post-operative cognitive decline (POCD). These individuals often stay in the hospital longer, have more complications, and are more likely to die. Recent clinical studies have shown the potential benefit of enhancing the cholinergic system among patients with both Alzheimer's disease and / or vascular dementia. Donepezil is currently being used to treat memory loss in patients with Alzheimer's disease.

This study will recruit 30 cognitively impaired adults aged 65 or older who are scheduled to have elective hip or knee replacement surgery at University Hospital. Participants will be randomized to receive either a three to six week supply of Donepezil or a matching placebo approximately 4 weeks prior to surgery. This study will evaluate the effect of Donepezil on delirium incidence and severity during hospitalization, global cognitive function, length of hospitalization, site of discharge, and adverse drug effects.

All material to be collected will be from interviews, questionnaires, and medical chart review. Some will be at baseline, during hospitalization, and 12 weeks post hospitalization and others will be daily during hospitalization. The International Study of Post-Operative Cognitive Decline battery of tests will be used in assessment, as will the CogHealth computerized battery.

Eligibility

Ages Eligible for Study:	65 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Community-dwelling individuals aged 65 or older
Scheduled for elective hip or knee replacement at University Hospital
Mild cognitive impairment, defined as:
- MMSE total score of 27 or less;
- normal performance of the activities of daily living tasks of the Bristol scale after excluding mobility related difficulties;
- no chart-based dementia diagnosis; and
- no history of ever being on dementia medications such as Memantine or any cholinesterase inhibitors
Consent to participate in the study

Exclusion Criteria:

Chart-based dementia diagnosis
MMSE score greater than 27
Difficulty performing the activities of daily living not related to mobility as measured by the Bristol scale
Current or past history of receiving dementia medications such as Memantine or any cholinesterase inhibitors (Tacrine, Donepezil, Rivastigmine, or Galantamine)
Metastatic cancer or other comorbid illnesses likely to reduce life expectancy to under 6 months
Multiple trauma or pathological fractures requiring acute hip or knee replacement
Aphasic, blind, or deaf
Use of neuroleptics one month prior to surgery
Allergy to donepezil
Inability to read and complete study tests and forms
Alcohol or drug dependence, defined as intake of more than 5 units of alcohol daily during the past 3 months
Not expected to be discharged from hospital or able to complete the 3-month postoperative test
Not competent to make medical decisions

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00182845

Locations

United States, Indiana
University Hospital, Clarian Health Partners
Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Pfizer

Investigators

Principal Investigator:

Malaz Boustani, MD, MPH

Regenstrief Institute, Indiana University Center for Aging Research

More Information

Publications:

Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth. 1998 Sep;81(3):449-62. Review. No abstract available.

Rasmussen LS. Defining postoperative cognitive dysfunction. Eur J Anaesthesiol. 1998 Nov;15(6):761-4. No abstract available.

Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. Erratum in: Lancet 1998 Jun 6;351(9117):1742.

Abildstrom H, Rasmussen LS, Rentowl P, Hanning CD, Rasmussen H, Kristensen PA, Moller JT. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiol Scand. 2000 Nov;44(10):1246-51.

Johnson T, Monk T, Rasmussen LS, Abildstrom H, Houx P, Korttila K, Kuipers HM, Hanning CD, Siersma VD, Kristensen D, Canet J, Ibanaz MT, Moller JT; ISPOCD2 Investigators. Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology. 2002 Jun;96(6):1351-7.

Study ID Numbers:	IA0078
Study First Received:	September 9, 2005
Last Updated:	February 28, 2008
ClinicalTrials.gov Identifier:	NCT00182845
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

dementia
MCI
Aricept
Adverse Effects

Hospital Acquired Complications
Cognitive Impairment
Aging

Study placed in the following topic categories:

Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Postoperative Complications
Mental Disorders
Donepezil
Neurologic Manifestations

Confusion
Dementia
Neurobehavioral Manifestations
Cognition Disorders
Delirium

Additional relevant MeSH terms:

Nootropic Agents
Cholinesterase Inhibitors
Neurotransmitter Agents
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Physiological Effects of Drugs
Nervous System Diseases
Enzyme Inhibitors
Cholinergic Agents
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009