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Alzheimer's DiseasePhase 4NCT00495820

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

A Phase 4 study testing Methylphenidate in people with Alzheimer's Disease and Apathy, run by VA Office of Research and Development at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 55 years and older
Conditions the study is for
Alzheimer's Disease, Apathy, Dementia
What is being tested?
Methylphenidate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteUnited States
Study dates
Aug 2007to Jun 2010
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of dementia of the Alzheimer type (DSM-IV Text Revision (TR) criteria)
  • Mini-mental state examination (MMSE) >18, but <29
  • Apathy Evaluation Scale (AES) score of more than 40
  • Ability to provide informed consent by either the patient or caregiver.
  • 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.
  • 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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • VA Medical Center, Omaha

    Omaha, Nebraska, 68105-1873

Other trials in United States

About this study

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.

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

  1. 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.

Being tested
Methylphenidate, Placebo
Keywords
Alzheimer's Disease, Apathy, Dementia, Methylphenidate
Medical subject headings
Alzheimer Disease, Lethargy, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethylphenidateDrug

    Also called Ritalin

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

  • PlaceboOther

    Standard inactive pill.

Study groups in NCT00495820
Study groupRoleWhat they receive
Arm 1ExperimentalMethylphenidate
Receives: Drug: Methylphenidate
Arm 2Placebo comparatorPlacebo
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At 12 weeks

Secondary outcomes (2)

  1. 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

    Measured: At 12 weeks

  2. 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.

    Measured: At 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionMar 2010
  4. Study completionJun 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00495820
Sponsor's protocol ID
MHBB-011-06F
Status last verified
Oct 2015
First submitted
2 Jul 2007
Last updated
20 Nov 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20220576

  • 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.

    PubMed 28945120

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Methylphenidate in people with Alzheimer's Disease and Apathy, run by VA Office of Research and Development at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Apathy Evaluation Scale Score at 12 Weeks (time frame: At 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00495820, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2015.

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