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

Dementia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00495820
• Other study ID #: MHBB-011-06F
• Status: Completed
• Phase: Phase 4
• First received: July 2, 2007
• Last updated: October 19, 2015
• Start date: August 2007
• Est. completion date: June 2010

Study information

• Verified date: October 2015
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Apathy
• Dementia

Intervention

Drug:
• Methylphenidate
Subject will receive 5mg twice a day for two weeks then 10mg twice a day until week 12 of the study.

Other:
• Placebo
Standard inactive pill.

Locations

Country	Name	City	State
United States	VA Medical Center, Omaha	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (1)

Padala PR, Burke WJ, Shostrom VK, Bhatia SC, Wengel SP, Potter JF, Petty F. Methylphenidate for apathy and functional status in dementia of the Alzheimer type. Am J Geriatr Psychiatry. 2010 Apr;18(4):371-4. doi: 10.1097/JGP.0b013e3181cabcf6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apathy Evaluation Scale Score 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	No
Secondary	Mini-mental State Examination (MMSE) 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	No
Secondary	Clinical Global Impression	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	No