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

NCT ID: NCT00495820

Last Updated: 2015-11-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-08-31

Study Completion Date

2010-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Alzheimer's Disease Apathy Dementia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Arm 1

Methylphenidate

Group Type EXPERIMENTAL

Methylphenidate

Intervention Type DRUG

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

Arm 2

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Standard inactive pill.

Interventions

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Methylphenidate

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

Intervention Type DRUG

Placebo

Standard inactive pill.

Intervention Type OTHER

Other Intervention Names

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Ritalin

Eligibility Criteria

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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
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Prasad R. Padala

Role: PRINCIPAL_INVESTIGATOR

VA Medical Center, Omaha

Locations

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VA Medical Center, Omaha

Omaha, Nebraska, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 20220576 (View on PubMed)

Padala PR, Padala KP, Lensing SY, Ramirez D, Monga V, Bopp MM, Roberson PK, Dennis RA, Petty F, Sullivan DH, Burke WJ. Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer's Disease: A Double-Blind, Randomized, Placebo-Controlled Trial. Am J Psychiatry. 2018 Feb 1;175(2):159-168. doi: 10.1176/appi.ajp.2017.17030316. Epub 2017 Sep 15.

Reference Type DERIVED
PMID: 28945120 (View on PubMed)

Other Identifiers

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MHBB-011-06F

Identifier Type: -

Identifier Source: org_study_id