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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00495820
First received: July 2, 2007
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

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 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.


Condition Intervention Phase
Alzheimer's Disease
Apathy
Dementia
Methylphenidate
Drug: Methylphenidate
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Methylphenidate for Apathy in Alzheimer's Dementia: A Controlled Study

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Hypothesis 1: Apathy Evaluation Scale Score at 12 weeks Hypothesis 2: Instrumental Activities of Daily Living, Zarit Burden Scale at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hypothesis 1: Neuropsychiatric Inventory, Clinical Global Impression Hypothesis 2: The Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D), Cornell Scale for Depression in Dementia [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: August 2007
Study Completion Date: June 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Methylphenidate
Drug: Methylphenidate
Subject will receive 5mg BID for two weeks then 10mg BID until week 12 of the study.
Other Name: Ritalin
Placebo Comparator: Arm 2
Placebo
Other: Placebo
Standard inactive pill.

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 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.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of dementia of the Alzheimer type (DSM-IV TR criteria)
  2. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00495820

Locations
United States, Nebraska
VA Medical Center, Omaha
Omaha, Nebraska, United States, 68105-1873
Sponsors and Collaborators
Investigators
Principal Investigator: Prasad R. Padala VA Medical Center, Omaha
  More Information

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00495820     History of Changes
Other Study ID Numbers: MHBB-011-06F
Study First Received: July 2, 2007
Last Updated: November 26, 2013
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Alzheimer's Disease
Apathy
Dementia
Methylphenidate

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Methylphenidate
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014