Apathy in Dementia Methylphenidate Trial (ADMET)

NCT01117181 | Completed Phase 2 Results DMC

• 1 other identifier: R01AG033032-01
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 3

Brief Summary

The Apathy in Dementia Methylphenidate Trial (ADMET) is a masked, placebo-controlled trial that will examine the efficacy and safety of methylphenidate for the treatment of clinically significant apathy in patients with Alzheimer's dementia.

Conditions

Apathy; Alzheimer's Disease

Keywords

Alzheimer's disease; Apathy; Methylphenidate; Dopaminergic agents; Apathy Evaluation Scale; Dementia

Outcome Measures

Primary Outcomes (2)

• Apathy Evaluation Scale (AES)

  Change in score of Apathy Evaluation Scale from baseline to 6 weeks; the minimum score is 18; the maximum score is 72. Higher scores indicate more severe apathy.

  baseline to 6 weeks

• Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change

  Proportion of individuals improving on Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (CGIC) from baseline to 6 weeks; 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.

  baseline to 6 weeks

Secondary Outcomes (6)

• Digit Span

  baseline and 6 weeks

• Mini-Mental State Exam (MMSE)

  baseline and 6 weeks

• Neuropsychiatric Inventory (NPI): Apathy Subscale

  baseline to week 6

• Vital Status

  vital status at 6 weeks

• Electrolytes

  6 weeks

Study Arms (2)

Methylphenidate

EXPERIMENTAL

Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention

Drug: Methylphenidate; Other: Psychosocial intervention

Placebo

PLACEBO COMPARATOR

matching placebo and psychosocial intervention

Drug: placebo; Other: Psychosocial intervention

Interventions

Methylphenidate DRUG

The target dose is 20 mg per day provided as two 10 mg doses administered orally. Patients will start by taking 10 mg daily (two 5 mg over-encapsulated tablets) for three days, at which time the dose will be increased to 20 mg per day (four 5 mg over-encapsulated tablets). In the event of significant side-effects, the dose will be reduced to a minimum of 10 mg per day. The study drug will be administered for 6 weeks.

Also known as: Ritalin

Methylphenidate

placebo DRUG

Patients will start with two capsules of placebo for three days, at which time the dose will be increased to four capsules. The dose may be reduced to a minimum of two capsules per day if there appears to be significant side-effects. Placebo will be administered for 6 weeks.

Also known as: dummy pill

Placebo

Psychosocial intervention OTHER

The psychosocial intervention will consist of three components: a counseling session, the provision of education materials, and 24-hour availability for crises. The counseling session, in which a trained study clinician will counsel the primary caregiver, lasts approximately 20-30 minutes, and consists of the following elements: * Review and adjustment of the patient and caregiver supportive care plans * Emotional support and opportunity to ventilate feelings * Counseling regarding specific caregiving skills * Assistance with problem solving of specific issues that the caregiver brings to the sessions * Answers for questions regarding the educational materials The educational materials will consist of a copy of the book The 36-Hour Day

Methylphenidate; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: 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 10-26 inclusive; MMSE scores above 26 in those who nevertheless meet criteria for AD may be allowed with Steering Committee approval on a case by case basis
• Clinically significant apathy for at least four weeks for which either 1) the frequency of apathy as assessed by the Neuropsychiatric Inventory (NPI) is 'Very frequently', or 2) 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 patient or surrogate (if the patient is unable to provide informed consent) and caregiver
• Availability of primary caregiver, who spends greater than ten hours a week with the patient and supervises his/her care, to accompany the patient to study visits and to participate in the study
• Sufficient fluency, of both the patient and caregiver, in written and spoken English to participate in study visits, physical exams, and outcome assessments
• No change to AD medications within the month preceding randomization, including starting, stopping, or dosage modifications

You may not qualify if:

• Meets criteria for Major Depressive Episode, by Diagnostic Statistical Manual of Mental Disorder - IV (TR) criteria
• Clinically significant agitation /aggression for which either 1) the frequency of agitation /aggression as assessed by the NPI is 'Very frequently', or 2) 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 1) the frequency of delusions as assessed by the NPI is 'Very frequently', or 2) 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 1) the frequency of hallucinations as assessed by the NPI is 'Very frequently', or 2) 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'
• Treatment with methylphenidate is contraindicated in the opinion of the study physician
• Failure of treatment with methylphenidate in the past for apathy after convincing evidence of an adequate trial as judged by study physician
• Treatment with a medication that would prohibit the safe concurrent use of methylphenidate such as monoamine oxidase inhibitors and tricyclic antidepressants
• Need for acute psychiatric hospitalization or is suicidal
• Uncontrolled hypertension (medication non-compliance or past 3 months with a diastolic reading of 105 as verified by compartment pressure of the rectus sheath (CPRS))
• Symptomatic coronary artery disease deemed to be significant by study physician at the time of screening
• Lack of appetite that results in significant unintentional weight loss as determined by the study physician in the last three months
• Significant communicative impairments
• Current participation in a clinical trial or in any study that may add significant burden or affect study outcomes
• Hyperthyroidism, advanced arteriosclerosis, symptomatic cardiovascular disease, serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or a family history of sudden death or death related to heart problems
• Glaucoma, pheochromocytoma, or known or suspected hypersensitivity to methylphenidate or its excipients

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• National Institute on Aging (NIA): collaborator
• Medical University of South Carolina: collaborator
• Johns Hopkins University: collaborator
• University of Toronto: collaborator

Study Sites (3)

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29406, United States

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Related Publications (1)

• Rosenberg PB, Lanctot KL, Drye LT, Herrmann N, Scherer RW, Bachman DL, Mintzer JE, ADMET Investigators. Safety and efficacy of methylphenidate for apathy in Alzheimer's disease: a randomized, placebo-controlled trial. J Clin Psychiatry. 2013 Aug;74(8):810-6. doi: 10.4088/JCP.12m08099.

  PMID: 24021498 DERIVED

MeSH Terms

Conditions

Lethargy; Alzheimer Disease; Dementia

Interventions

Methylphenidate; Psychosocial Intervention

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; 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; Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Anne Casper, MA
• Organization: Johns Hopkins

ashankli@jhsph.edu

410-955-8183

Study Officials

• Roberta Scherer, PhD

  Johns Hopkins University Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

• Jacobo Mintzer, MD, MBA

  Medical University of South Carolina

  STUDY CHAIR

• Paul Rosenberg, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Krista Lanctot, PhD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: May 4, 2010
• First Posted: May 5, 2010
• Study Start: June 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: June 12, 2018
• Results First Posted: May 10, 2013

Record last verified: 2018-06

Locations

CA (1); US (2)