Donepezil and the Risk of Falls in Seniors With Cognitive Impairment

NCT00934531 | Completed

• 2 other identifiers: R-09-42716086
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Compared with cognitively normal older adults, those with mild cognitive problems (MCI) have a two-fold higher rate of falls, sustain more fractures, and have a higher rate of mortality due to falls. Why older adults with cognitive problems fall more frequently is not completely understood. What is known, however, is that attention is a necessary cognitive resource for normal walking and impairments in attention are associated with increased risk of falls in older adults. It has been suggested that cholinesterase inhibitors (ChEI), medications used for treatment of dementia, may improve motor function and walking (gait performance). Since ChEI are known to improve attention, we hypothesized that ChEI will reduce falls risk in people with MCI by improving their gait velocity, improving their balance, and reducing their gait variability; a well-established risk factor for falls. In the proposed study, we will evaluate the effect of donepezil (ChEI) on gait velocity, gait variability, and the balance on 140 elderly individuals with MCI (70 intervention and 70 controls). Gait variables will be measured using an electronic walkway, and balance confidence using a validated scale (Activities-Specific Balance Confidence Scale; ABC) over four months. By characterizing and understanding the effects of cognitive enhancers on fall risk in older adults with cognitive impairments, we will be able to pave the way for a new approach to fall prevention in this population. We would establish that medications that augment cognitive function could be a complementary therapeutic option for reducing fall risk in people with MCI. This may lead to new approaches to prevent and treat fall risk in this population, which will lead to improve the autonomy and quality of life of seniors in early stage of dementia, and a decreased burden for the Ontario health care system.

Conditions

Falls; Gait; Balance; Mild Cognitive Impairment (MCI)

Keywords

Mild Cognitive Impairment (MCI); Falls; donepezil; gait variability

Outcome Measures

Primary Outcomes (1)

• Improvements in gait performance (Combined outcome: increase in gait velocity-cm/second- and/or reduction in gait variability assessed as standard deviation (SD) and coefficient of variation (CoV).

  6 months

Secondary Outcomes (1)

• Improvement in: 1. Balance confidence 2. Balance sway 3. Attention 4. Executive function 5. Reduction of number of Falls.

  6 months

Study Arms (2)

Donepezil

EXPERIMENTAL

participants with MCI receiving donepezil

Drug: Donepezil

Placebo

PLACEBO COMPARATOR

Participants with MCI receiving placebo

Drug: Donepezil

Interventions

Donepezil DRUG

Participants with MCI will be randomized to either the experimental (donepezil) or placebo arm of the study. Experimental Arm: Participants with MCI will receive 5 mg/day of donepezil p.o. for 4 weeks, and thereafter 10 mg/day of donepezil p.o. for a period of 5 months, yielding a total period of intervention of 6 months from baseline. Placebo Arm: Participants with MCI will receive a matched placebo p.o. for 4 weeks, and thereafter will receive a new matched placebo p.o. for the next 5 months, yielding a total period of intervention of 6 months from baseline.

Also known as: donepezil (Aricept)

Donepezil; Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65-100
• Male or Female
• Having Mild Cognitive Impairment (diagnosed using criteria validated by Petersen et. al)
• Acceptable Body Mass Index (BMI) range: 18-30
• Acceptable blood pressure (Systolic: 110-160, Diastolic: 50-110)
• Able to walk independently 10 meters without any gait aid
• Able to travel to Aging Brain and Memory Clinic for the assessments

You may not qualify if:

• Unable to understand English
• Low body weight (less than 99lb/45kg)
• Possible diagnosis of Alzheimer's Disease
• Use of herbal preparations such as St. John's Wort and ginko biloba
• History of drug or alcohol abuse/dependence
• History of psychiatric illness within the last two years, including depression
• Parkinsonism or any neurological disorder with residual motor deficit (e.g.: stroke, epilepsy)
• Musculoskeletal disorder detected by clinical examination which affects gait performance
• Active osteoarthritis affecting the lower limbs (American College of Rheumatology criteria)
• Use of psychotropic medication, which can affect motor performance
• Use of an anticholinergic agent (benztropines), other acetylcholinesterase inhibitors or cholinergic agents (bethanechol)
• Depression (score above 8/15 on the Geriatric Depression Scale - GDS)
• Comorbidities which may contradict use of ChEIs
• History of chronic bradycardia or sick sinus syndrome
• Severe COPD and/or asthma

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

St. Joseph's Health Care London, Parkwood Hospital

London, Ontario, N6C 5J1, Canada

Location

Related Publications (5)

• Montero-Odasso M, Wells J, Borrie M. Can cognitive enhancers reduce the risk of falls in people with dementia? An open-label study with controls. J Am Geriatr Soc. 2009 Feb;57(2):359-60. doi: 10.1111/j.1532-5415.2009.02085.x. No abstract available.

  PMID: 19207156 BACKGROUND

• Montero-Odasso M. The value of gait velocity test for high-function populations. J Am Geriatr Soc. 2006 Dec;54(12):1949-50; author reply 1950. doi: 10.1111/j.1532-5415.2006.00952.x. No abstract available.

  PMID: 17198509 BACKGROUND

• Montero-Odasso M, Schapira M, Soriano ER, Varela M, Kaplan R, Camera LA, Mayorga LM. Gait velocity as a single predictor of adverse events in healthy seniors aged 75 years and older. J Gerontol A Biol Sci Med Sci. 2005 Oct;60(10):1304-9. doi: 10.1093/gerona/60.10.1304.

  PMID: 16282564 BACKGROUND

• Montero-Odasso M, Speechley M, Chertkow H, Sarquis-Adamson Y, Wells J, Borrie M, Vanderhaeghe L, Zou GY, Fraser S, Bherer L, Muir-Hunter SW. Donepezil for gait and falls in mild cognitive impairment: a randomized controlled trial. Eur J Neurol. 2019 Apr;26(4):651-659. doi: 10.1111/ene.13872. Epub 2018 Dec 26.

  PMID: 30565793 BACKGROUND

• Montero-Odasso M, Wells JL, Borrie MJ, Speechley M. Can cognitive enhancers reduce the risk of falls in older people with mild cognitive impairment? A protocol for a randomised controlled double blind trial. BMC Neurol. 2009 Aug 12;9:42. doi: 10.1186/1471-2377-9-42.

  PMID: 19674471 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• Manuel Montero Odasso, MD, PhD

  The University of Western Ontario, Dept. of Medicine, Div. of Geriatric Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Geriatrician/Clinician Scientist

Study Record Dates

• First Submitted: July 7, 2009
• First Posted: July 8, 2009
• Study Start: September 1, 2009
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: January 7, 2019

Record last verified: 2019-01

Locations

CA (1)