Apathy in Dementia Methylphenidate Trial 2

NCT02346201 | Completed Phase 3 Results DMC

• 2 other identifiers: ADMET2R01AG046543
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 10

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.

Conditions

Apathy; Alzheimer's Disease

Outcome Measures

Primary Outcomes (2)

• Neuropsychiatric Inventory (NPI)

  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)

  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

Study Arms (2)

Methylphenidate

ACTIVE COMPARATOR

Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention

Drug: Methylphenidate

Placebo

PLACEBO COMPARATOR

Matching over-encapsulated placebo and psychosocial intervention

Drug: Placebo

Interventions

Methylphenidate DRUG

Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention

Also known as: Ritalin

Methylphenidate

Placebo DRUG

Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• National Institute on Aging (NIA): collaborator

Study Sites (10)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

University of Arkansas

Little Rock, Arkansas, 72114, United States

Location

Yale Alzheimer's Disease Research Unit

New Haven, Connecticut, 06510, United States

Location

Emory

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

University of Rochester

Rochester, New York, 14620, United States

Location

Wake Forest

Winston-Salem, North Carolina, 27106, United States

Location

University Hospitals- Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Roper-St. Francis Healthcare

Charleston, South Carolina, 29401, United States

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Related Publications (4)

• Sankhe K, Ruthirakuhan M, Andreazza AC, Brawman-Mintzer O, Craft S, Herrmann N, Ismail Z, Lerner AJ, Levey AI, Mintzer J, Padala PR, Perin J, Porsteinsson AP, Rosenberg PB, Shade D, Tumati S, van Dyck CH, Lanctot KL. Peripheral biomarkers associated with apathy and predicting response to methylphenidate: Secondary analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET2) study. Int Psychogeriatr. 2026 Jan 10:100181. doi: 10.1016/j.inpsyc.2025.100181. Online ahead of print.

  PMID: 41521126 DERIVED

• Lanctot KL, Chen C, Mah E, Kiss A, Li A, Shade D, Scherer RW, Vieira D, Coulibaly H, Rosenberg PB, Lerner AJ, Padala PR, Brawman-Mintzer O, van Dyck CH, Porsteinsson AP, Craft S, Levey A, Burke WJ, Mintzer J, Herrmann N. Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2). Int Psychogeriatr. 2023 Nov;35(11):664-672. doi: 10.1017/S1041610223000327. Epub 2023 Apr 17.

  PMID: 37066690 DERIVED

• Mintzer J, Lanctot KL, Scherer RW, Rosenberg PB, Herrmann N, van Dyck CH, Padala PR, Brawman-Mintzer O, Porsteinsson AP, Lerner AJ, Craft S, Levey AI, Burke W, Perin J, Shade D; ADMET 2 Research Group. Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial. JAMA Neurol. 2021 Nov 1;78(11):1324-1332. doi: 10.1001/jamaneurol.2021.3356.

  PMID: 34570180 DERIVED

• Scherer RW, Drye L, Mintzer J, Lanctot K, Rosenberg P, Herrmann N, Padala P, Brawman-Mintzer O, Burke W, Craft S, Lerner AJ, Levey A, Porsteinsson A, van Dyck CH; ADMET 2 Research Group. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a randomized controlled trial. Trials. 2018 Jan 18;19(1):46. doi: 10.1186/s13063-017-2406-5.

  PMID: 29347996 DERIVED

MeSH Terms

Conditions

Lethargy; Alzheimer Disease

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jennifer Jones, Research Coordinator
• Organization: Johns Hopkins School of Public Health

jejones@jhu.edu

44377086812

Study Officials

• Jacobo Mintzer, MD

  Medical University of South Carolina

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2015
• First Posted: January 26, 2015
• Study Start: January 1, 2016
• Primary Completion: July 15, 2020
• Study Completion: July 15, 2020
• Last Updated: June 13, 2023
• Results First Posted: June 13, 2023

Record last verified: 2023-06

Locations

US (9); CA (1)