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Apathy in Dementia Methylphenidate Trial 2 (ADMET2)

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ClinicalTrials.gov Identifier: NCT02346201
Recruitment Status : Completed
First Posted : January 26, 2015
Last Update Posted : August 11, 2020
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Johns Hopkins Bloomberg School of Public Health

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Apathy Alzheimer's Disease Drug: Methylphenidate Drug: Placebo Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Apathy in Dementia Methylphenidate Trial 2
Study Start Date : January 2016
Actual Primary Completion Date : July 15, 2020
Actual Study Completion Date : July 15, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. Clinical Global Impression of Change (CGIC) [ Time Frame: At month 6 ]
    Odds of having a given rating or better on the Alzheimer's Disease Cooperative Study-CGIC ratings at month 6 as evaluated by a study clinician who records his/her clinical impression of change from baseline on a seven-item scale


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02346201


Locations
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United States, Arizona
Banner Alzheimer's Institute
Phoenix, Arizona, United States, 85006
United States, Arkansas
University of Arkansas
Little Rock, Arkansas, United States, 72114
United States, Connecticut
Yale Alzheimer's Disease Research Unit
New Haven, Connecticut, United States, 06510
United States, Georgia
Emory
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21224
United States, New York
University of Rochester
Rochester, New York, United States, 14620
United States, North Carolina
Wake Forest
Winston-Salem, North Carolina, United States, 27106
United States, Ohio
University Hospitals- Case Medical Center
Cleveland, Ohio, United States, 44106
United States, South Carolina
Roper-St. Francis Healthcare
Charleston, South Carolina, United States, 29401
Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Sponsors and Collaborators
Johns Hopkins Bloomberg School of Public Health
National Institute on Aging (NIA)
Investigators
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Study Chair: Jacobo Mintzer, MD Medical University of South Carolina
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Johns Hopkins Bloomberg School of Public Health
ClinicalTrials.gov Identifier: NCT02346201    
Other Study ID Numbers: ADMET2
R01AG046543 ( U.S. NIH Grant/Contract )
First Posted: January 26, 2015    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
 Methylphenidate
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents