Treatment of Apathy in Alzheimer's Disease With Modafinil

This study examined the effects of modafinil on apathetic symptomatology, performance of activities of daily living (ADLs) and caregiver burden in individuals with Alzheimer's disease (AD).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease; Apathy
• Intervention / Treatment: Drug: Placebo; Drug: Modafinil

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 95 years (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of mild to moderate stage Probable Alzheimer's disease
• on a stable dose of a cholinesterase inhibitor medication for at least 30 days
• clinically elevated levels of apathy as measured by the Frontal Systems Behavior Scale

Exclusion Criteria:

• diagnosis of Major Depression
• focal brain lesion on neuroimaging
• history of significant substance abuse
• history of significant head trauma with loss if consciousness >10 minutes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Cholinesterase inhibitor only	Drug: Placebo; 100 mg in the morning for the first week and 200 mg in the morning for the remaining seven weeks
Experimental: Cholinesterase Plus Modafinil	Drug: Modafinil; 100 mg in the morning for the first week and 200 mg in the morning for the remaining seven weeks; Other Names: Provigil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apathy	The Frontal Systems Behavior Scale. Raw scores are converted to T-Scores using published norms. T-Scores have a mean of 50 and a standard deviation of 10. T-scores less than or equal to 64 are within average range. T-scores equal to or greater than 65 are indicative of a clinically significant problem. Higher scores indicate greater problem severity.	at baseline
Apathy	The Frontal Systems Behavior Scale.Raw scores are converted to T-Scores using published norms. T-Scores have a mean of 50 and a standard deviation of 10. T-scores less than or equal to 64 are within the average range. T-scores equal to or greater than 65 are indicative of a clinically significant problem. Higher scores indicate greater problem severity.	after 8 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lawton Brody Activities of Daily Living Questionnaire	Caregiver reported performance of personal and instrumental activities of daily living (ADLs. There are 6 personal ADLs (i.e. dressing, grooming, eating, etc) and 8 instrumental ADLs (i.e. managing finances, transportation, food preparation) which are assessed. Each item is awarded 2 points for fully independent, 1 point for minimal or moderate support required, and 0 points for full support. Maximum score for independence with all personal and instrumental ADL's is 28.	at baseline
The Direct Assessment of Functional Status Scale	A direct, examiner observed assessment of basic and instrumental activities of daily living. Participants are awarded points for correct performance of activities. Raw score is used for statistical comparison.	at baseline
Zarit Burden Inventory	Measure of Caregiver Burden. Caregiver rates each item assessing burden on a 0 to 4 point scale with higher numbers reflecting more frequent occurence of the behavior or feeling being assessed.	at baseline
Lawton Brody Activities of Daily Living Questionnaire	Caregiver reported performance of personal and instrumental activities of daily living (ADLs. There are 6 personal ADLs (i.e. dressing, grooming, eating, etc) and 8 instrumental ADLs (i.e. managing finances, transportation, food preparation) which are assessed. Each item is awarded 2 points for fully independent, 1 point for minimal or moderate support required, and 0 points for full support. Maximum score for independence with all personal and instrumental ADL's is 28.	after 8 weeks of treatment
The Direct Assessment of Functional Status Scale	A direct, examiner observed assessment of basic and instrumental activities of daily living. Participants are awarded points for correct performance of activities. Raw score is used for statistical comparison.	after 8 weeks of treatment
Zarit Burden Inventory	Measure of Caregiver Burden. Caregiver rates each item assessing burden on a 0 to 4 point scale with higher numbers reflecting more frequent occurence of the behavior or feeling being assessed.	after 8 weeks of treatment

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: National Institute of Mental Health (NIMH); Cephalon
• Investigators: Principal Investigator: Laura L Frakey, Ph.D., Memorial Hospital of Rhode Island

Publications and helpful links

General Publications

• Frakey LL, Salloway S, Buelow M, Malloy P. A randomized, double-blind, placebo-controlled trial of modafinil for the treatment of apathy in individuals with mild-to-moderate Alzheimer's disease. J Clin Psychiatry. 2012 Jun;73(6):796-801. doi: 10.4088/JCP.10m06708. Epub 2012 May 15.

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: July 28, 2010
• First Submitted That Met QC Criteria: July 28, 2010
• First Posted (Estimate): July 29, 2010

Study Record Updates

• Last Update Posted (Estimate): March 4, 2011
• Last Update Submitted That Met QC Criteria: February 9, 2011
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Alzheimer's disease; caregiver burden; apathy; activities of daily living performance
• 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; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: 1F32MH075583-01 (U.S. NIH Grant/Contract)