Methylphenidate for Apathy in Alzheimer's Dementia: A Controlled Study

October 19, 2015 updated by: VA Office of Research and Development

The purpose of the study is to determine the efficacy of methylphenidate over placebo in treating apathy in patients with Alzheimer's dementia. Apathy is one of the earliest and most profound disturbances that occur in Alzheimer's dementia (AD).

Hypotheses: 1. Methylphenidate (MPH) will improve apathy significantly more than placebo in AD.

2. Successful treatment of apathy will improve Instrumental Activities of Daily Living (IADLs), and caregiver burden.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Objective: Apathy is one of the earliest and most profound disturbances that occur in Alzheimer's dementia (AD). Based on promising preliminary data from our open-label pilot study we propose a double blind, placebo-controlled randomized clinical trial of methylphenidate for treatment of apathy in AD.

Research Design: Randomized double blind, placebo-controlled study which will evaluate the effect of methylphenidate on apathy and also the impact of improvement of apathy on caregiver burden and functional status.

Hypotheses: 1. Methylphenidate will improve apathy significantly more than placebo in AD.

2. Successful treatment of apathy will improve Instrumental Activities of Daily Living (IADLs), and caregiver burden.

Methodology: 60 patients with apathy in the context of AD will be recruited over the next three years. In our proposed study patients will be recruited from relevant clinics at the Omaha Veterans Affairs Medical Center (VAMC) including clinics in Geriatric Psychiatry, Neurology, Primary Care and Geriatric Medicine. 30 patients each with AD and apathy will be randomly assigned to placebo or MPH. All patients in the methylphenidate arm will be started at 5mg twice daily and titrated to 10mg twice daily at two weeks. Patients will be continued in this arm for 12 weeks followed by a 2-week discontinuation phase. Patients will be assessed on regular intervals using the Apathy Evaluation Scale, Instrumental Activities of Daily Living, Zarit Burden Scale and Mini Mental State Examination.

Findings: None, the study is not complete.

Clinical Relationships: While memory is the key cognitive problem in AD, apathy is the key behavioral problem. Apathy is characterized by indifference, disengagement, passivity, and lack of enthusiasm, interest, empathy and interpersonal involvement. Apathy is the most common, one of the earliest and probably the most persistent of behavioral problems in AD. Apathy is the most disturbing behavior to caregivers and has the greatest impact on functional status and caregiver burden.

Despite this, apathy as a behavioral problem has largely been neglected. Most of the research directed towards behavioral problems in dementia is targeted towards more visible behaviors such as agitation, and psychosis. Remarkably, there are no published randomized, double blind, placebo controlled studies in the treatment of apathy associated with AD.

Impact/Significance: Around 1.4 million veterans suffer from apathy in association with AD. Apathy is a strong predictor for functional decline and caregiver burden. Treatment of apathy is remarkably understudied and is absolutely critical to allow veterans to maximize their functional status, social engagement and quality of life, and thus delaying placement in assisted living or nursing home settings.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68105-1873
        • VA Medical Center, Omaha

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of dementia of the Alzheimer type (DSM-IV Text Revision (TR) criteria)
  2. Mini-mental state examination (MMSE) >18, but <29
  3. Apathy Evaluation Scale (AES) score of more than 40
  4. Ability to provide informed consent by either the patient or caregiver.
  5. If subjects are being treated with antidepressants, they should be on a stable dose of antidepressants for at least two months prior to the enrollment into the study.
  6. If subjects are being treated with cholinesterase inhibitors and memantine, they should be on stable dose of those medications at least four months prior to the enrollment into the study.

Exclusion Criteria:

  1. Patient currently taking methylphenidate or hypersensitivity or prior significant adverse events with methylphenidate.
  2. Patients currently taking Adderall (amphetamine mixed salts) or Dexedrine (dextroamphetamine sulphate) or any other amphetamine product.
  3. Uncontrolled hypertension (BP > 140/90) or tachycardia (100) at screening visit
  4. Patients with frontotemporal dementia
  5. Patients meeting criteria for Major Depressive Disorder on the Mini International Neuropsychiatric Inventory (MINI)
  6. Patients with active psychosis as determined by MINI
  7. Patients currently being treated with antipsychotics
  8. History of uncontrolled seizure disorder
  9. History of malignant hypertension, symptomatic cardiovascular disease, cardiomyopathy, known structural cardiac defect or medically unstable arrhythmias.
  10. History of Tourette's syndrome or presence of motor tics
  11. Patients with glaucoma
  12. Patients taking monoamine oxidase inhibitors (MAOIs)
  13. Patient taking clonidine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Arm 2
Placebo
Other: Placebo
Standard inactive pill.
Experimental: Arm 1
Methylphenidate
Drug: Methylphenidate
Subject will receive 5mg twice a day for two weeks then 10mg twice a day until week 12 of the study.
Other Names:
  • Ritalin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Apathy Evaluation Scale Score at 12 Weeks
Time Frame: At 12 weeks
The Apathy Evaluation Scale (AES) has been specifically developed to assess apathy and discriminate it from depression. This 18 item scale with score ranging from 18 to 72, assesses apathy in behavioral, cognitive and emotional domains over the previous four weeks. Higher scores indicate worsening apathy.
At 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mini-mental State Examination (MMSE) at 12 Weeks
Time Frame: At 12 weeks
Mini-mental State Examination (MMSE) is a commonly used screening measure for cognition with questions pertaining to orientation, registration, recall, visuo-spatial construction, attention span etc. Score on MMSE ranges from 0-30, higher scores indicating improving cognition
At 12 weeks
Clinical Global Impression
Time Frame: At 12 weeks
The Clinical Global Impression scale is an observational scale of global evaluation, which assesses the change in degree of illness in relation to the original assessment. The severity sub-scale reported below ranges from 1-7 wherein higher scores indicate worsening severity of illness.
At 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Prasad R. Padala, VA Medical Center, Omaha

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

July 2, 2007

First Submitted That Met QC Criteria

July 2, 2007

First Posted (Estimate)

July 3, 2007

Study Record Updates

Last Update Posted (Estimate)

November 20, 2015

Last Update Submitted That Met QC Criteria

October 19, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MHBB-011-06F

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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