Apathy in Dementia Methylphenidate Trial 2 (ADMET2)

June 9, 2023 updated by: Johns Hopkins Bloomberg School of Public Health
Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is a Phase III, placebo-controlled, masked, 6 month, multi-center randomized clinical trial sponsored by National Institutes of Aging involving 200 participants with Alzheimer's disease (AD). ADMET 2 is designed to examine the efficacy and safety of methylphenidate as treatment for clinically significant apathy in AD participants. ADMET 2 will enroll participants from real world settings such as outpatient, nursing home, and assisted living facilities and will examine the effects of methylphenidate on apathy and cognition. ADMET 2 will also conduct careful safety monitoring.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

ADMET 2 will examine in a masked, randomized trial the efficacy of methylphenidate for the treatment of clinically significant apathy in participants with Alzheimer's dementia. Efficacy will be assessed as the change in Neuropsychiatric Inventory Apathy subscale (NPI apathy) from baseline to 6 months and score on the Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (CGIC) scale at 6 months.

ADMET 2 will also examine the safety of methylphenidate for the treatment of clinically significant apathy in participants with Alzheimer's disease by measuring vital signs, electrolyte panels, adverse event reports, and electrocardiograms. Safety will also be measured by examining neuropsychiatric symptoms other than apathy using the Neuropsychiatric Inventory (NPI).

Changes from baseline to 6 months in other neuropsychological assessments as measured using the Dementia Apathy Interview and Rating (DAIR) scale will also be assessed.

Cost-effectiveness will be measured by assessing quality of life and economic assessment and cognitive changes using a cognitive battery that includes the Mini Mental State Exam (MMSE) and other scales.

A biomarker sub-study initiated part-way through the main trial will collect information on blood-based biomarkers, including microRNA, markers of oxidative stress, inflammation, neuronal loss and lipidomics.

Study Type

Interventional

Enrollment (Actual)

200

Phase

  • Phase 3

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

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • Sunnybrook Health Sciences Centre
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner Alzheimer's Institute
    • Arkansas
      • Little Rock, Arkansas, United States, 72114
        • University of Arkansas
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale Alzheimer's Disease Research Unit
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins University
    • New York
      • Rochester, New York, United States, 14620
        • University of Rochester
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27106
        • Wake Forest
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals- Case Medical Center
    • South Carolina
      • Charleston, South Carolina, United States, 29401
        • Roper-St. Francis Healthcare

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  • Possible or probable Alzheimer's disease (National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria), with Mini-Mental State Exam (MMSE) score of 10-28 inclusive

  • Clinically significant apathy for at least four weeks for which either

    • the frequency of apathy as assessed by the Neuropsychiatric Inventory (NPI) is 'Very frequently', or
    • the frequency of apathy as assessed by the NPI is 'Frequently' or 'Often' AND the severity of apathy as assessed by the NPI is 'Moderate' or 'Marked'
  • A medication for apathy is appropriate, in the opinion of the study physician
  • Provision of informed consent for participation in the study by potential participant or surrogate (with participant assent if the potential participant is unable to provide informed consent) and caregiver
  • Availability of primary caregiver, who spends greater than ten hours a week with the potential participant and supervises his/her care, to accompany the potential participant to study visits and to participate in the study
  • Sufficient fluency, of both the potential participant and caregiver, in written and spoken English to participate in study visits, physical exams, and outcome assessments
  • If female, woman must be post-menopausal for at least 2 years or have had a hysterectomy

Exclusion criteria

  • Currently meets criteria for Major Depressive Episode, by Diagnostic Statistical Manual of Mental Disorder - IV (TR) criteria

  • Clinically significant agitation /aggression for which either

    • the frequency of agitation /aggression as assessed by the NPI is 'Very frequently', or
    • the frequency of agitation /aggression as assessed by the NPI is 'Frequently' AND the severity of the agitation as assessed by the NPI is 'Moderate', or 'Marked'

  • Clinically significant delusions for which either

    • the frequency of delusions as assessed by the NPI is 'Very frequently', or
    • the frequency of delusions as assessed by the NPI is 'Frequently' AND the severity of the delusions as assessed by the NPI is 'Moderate', or 'Marked'

  • Clinically significant hallucinations for which either

    • the frequency of hallucinations as assessed by the NPI is 'Very frequently', or
    • the frequency of hallucinations as assessed by the NPI is 'Frequently' AND the severity of the hallucinations as assessed by the NPI is 'Moderate', or 'Marked'
  • Change to AD medications within the month preceding randomization, including starting, stopping, or dosage modifications
  • Change in anti-depressant (except for trazodone used for sleeping difficulties as described below) use within the 30 days preceding randomization or a period of time equal to 5 half-lives of drug, whichever period of time is longer
  • Use of trazodone > 50mg or lorazepam > 0.5mg or for indications other than sleeping difficulties within the 30 days preceding randomization or a period of time equal to 5 half-lives of drug, whichever period of time is longer. Other benzodiazepines are prohibited in the past 30 days or within 5 half-lives, whichever period of time is longer.
  • Failure of treatment with methylphenidate in the past for apathy after convincing evidence of an adequate trial as judged by study physician
  • Currently taking any amphetamine product, an antipsychotic, bupropion, or any medication that would prohibit the safe concurrent use of methylphenidate, including but not limited to monoamine oxidase inhibitors and tricyclic antidepressants within the 30 days preceding randomization or a period of time equal to 5 half-lives of drug, whichever period of time is longer
  • Need for acute psychiatric hospitalization or is suicidal in the opinion of the study physician
  • Significant communicative impairments that would affect participation in clinical trial
  • Central nervous system abnormalities (e.g., cerebral aneurysm), seizures (convulsions, epilepsy), Tourette's syndrome or presence of motor tics, or abnormal electroencephalograms
  • Lack of appetite that results in significant unintentional weight loss as determined by the study physician in the last three months
  • Uncontrolled hyperthyroidism
  • Any cardiovascular or cerebrovascular abnormality deemed to be clinically significant by the study physician, tachycardia (heart rate > 100 beats per minute), or uncontrolled hypertension (defined as medication non-compliance or past 3 months with a diastolic reading > 105 mm Hg), at the time of screening
  • Closed angle glaucoma or pheochromocytoma
  • Women with childbearing potential
  • Current participation in a clinical trial or study that may add significant burden or affect study outcomes
  • Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the potential participant to enroll in the trial, including, but not limited to, contraindication to treatment with methylphenidate.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Methylphenidate
Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention
Drug: Methylphenidate
Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention
Other Names:
  • Ritalin
Placebo Comparator: Placebo
Matching over-encapsulated placebo and psychosocial intervention
Drug: Placebo
Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuropsychiatric Inventory (NPI)
Time Frame: baseline to 6 months

Mean difference in change from baseline to 6 months in the NPI apathy subscale scores as administered by certified personnel to the study caregiver.

SEVERITY is graded 1 to 3 and FREQUENCY is graded 1 to 4. The overall score for the domain is the product of the severity and frequency which ranges from 1 to 12 with higher scores indicating more apathy.
baseline to 6 months
Percentage of Participants With Change in Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (CGIC)
Time Frame: Baseline to month 6
Percentage of individuals improving on Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (CGIC) from baseline to 6 months; the CGIC is a 7-point Likert scale used to rate each patient with the following scores: "marked worsening"(7), "moderate worsening" (6), "minimal worsening"(5), "no change"(4), "minimal improvement"(3), "moderate improvement"(2), "marked improvement"(1). Ratings were based on an interview with the caregiver and an examination of the patient. The CGIC requires the clinician to consider a number of aspects of apathy, such as level of initiative, level of interest, and emotional engagement. Reported data is the percentage of participants with minimal/moderate/marked improvement.
Baseline to month 6

Collaborators and Investigators

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

Sponsor

Johns Hopkins Bloomberg School of Public Health

Collaborators

National Institute on Aging (NIA)

Investigators

  • Study Chair: Jacobo Mintzer, MD, Medical University of South Carolina

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

January 1, 2016

Primary Completion (Actual)

July 15, 2020

Study Completion (Actual)

July 15, 2020

Study Registration Dates

First Submitted

January 20, 2015

First Submitted That Met QC Criteria

January 20, 2015

First Posted (Estimated)

January 26, 2015

Study Record Updates

Last Update Posted (Actual)

June 13, 2023

Last Update Submitted That Met QC Criteria

June 9, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADMET2
  • R01AG046543 (U.S. NIH Grant/Contract)

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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