Apathy in Dementia Methylphenidate Trial (ADMET)

NCT ID: NCT01117181

Last Updated: 2018-06-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2012-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The Apathy in Dementia Methylphenidate Trial (ADMET), funded by the National Institute of Aging, is a Phase II, placebo-controlled, masked, 3-center randomized clinical trial. ADMET will enroll 60 patients with Alzheimer's disease (AD) and significant apathy from outpatient, nursing home, and assisted living facilities along with their primary caregiver. Eligible and willing patients will be randomly assigned to methylphenidate (20 mg per day) or placebo. At baseline and each in-person follow-up visit, all caregivers and patients will be provided with a standardized psychosocial intervention consisting of a counseling session, provision of educational materials, and 24-hour availability for crises. Efficacy and safety outcomes will be measured at baseline and at in-person follow-up visits at 2, 4, and 6 weeks following randomization. Telephone contact will take place at 1, 3, and 5 weeks after randomization.

ADMET has 80% power to detect a difference of at least 3.3 in change in the Apathy Evaluation Scale scores between the two treatment groups. It also has 80% power to detect an absolute difference of 35% or more in the change in the proportion of study participants improving on te Clinical Global Impression of Change, given that 20% to 305 of participants in the placebo group show improvement.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Apathy Alzheimer's Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Methylphenidate

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

Group Type EXPERIMENTAL

Methylphenidate

Intervention Type 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.

Psychosocial intervention

Intervention Type 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

Placebo

matching placebo and psychosocial intervention

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type 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.

Psychosocial intervention

Intervention Type 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Methylphenidate

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.

Intervention Type DRUG

placebo

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.

Intervention Type DRUG

Psychosocial intervention

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

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Ritalin dummy pill

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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 10-26 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
* Treatment with stable doses of selective serotonin reuptake inhibitor antidepressants(SSRIs) is appropriate if stable for 3 months prior to randomization. Other psychotropics(with the exclusion of antipsychotics), if stable for 3 months, may be allowed only with Steering Committee approval on a case by case basis.

Exclusion Criteria

* 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 psychotropic medications in the 2 weeks prior to randomization with the exception of approved treatments for dementia (ChEIs and memantine), selective serotonin reuptake inhibitor antidepressants, and trazodone (if used as an aid to facilitate sleep and not as an antidepressant); other psychotropics (with the exclusion of antipsychotics), if stable for 3 months, may be allowed only with Steering Committee approval on a case by case basis. Note that antipsychotics are expressly prohibited.
* 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
* Central Nervous System (CNS) abnormalities (e.g., cerebral aneurysm) and/or other vascular abnormalities such as vasculitis or pre-existing stroke, motor tics or a family history or diagnosis of Tourette's syndrome, seizures (convulsions, epilepsy), or abnormal EEGs
* Any condition that, in the opinion of the study physician, makes it medically inappropriate or risky for the patient to enroll in the trial
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

University of Toronto

OTHER

Sponsor Role collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Roberta Scherer, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University Bloomberg School of Public Health

Jacobo Mintzer, MD, MBA

Role: STUDY_CHAIR

Medical University of South Carolina

Paul Rosenberg, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Krista Lanctot, PhD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 24021498 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01AG033032-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01AG033032-01

Identifier Type: NIH

Identifier Source: org_study_id

View Link

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Methylphenidate Treatment of Cancer-Related Fatigue
NCT00758407 COMPLETED PHASE2/PHASE3