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Apathy in Dementia Methylphenidate Trial (ADMET)

Phase 2
Completed
Conditions
Apathy
Alzheimer's Disease
Interventions
Drug: placebo
Other: Psychosocial intervention
Registration Number
NCT01117181
Lead Sponsor
Johns Hopkins Bloomberg School of Public Health
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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MethylphenidatePsychosocial interventionMethylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention
Placeboplacebomatching placebo and psychosocial intervention
PlaceboPsychosocial interventionmatching placebo and psychosocial intervention
MethylphenidateMethylphenidateMethylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention
Primary Outcome Measures
NameTimeMethod
Apathy Evaluation Scale (AES)baseline to 6 weeks

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.

Alzheimer's Disease Cooperative Study- Clinical Global Impression of Changebaseline to 6 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Digit Spanbaseline and 6 weeks

Change in Digit Span from baseline to 6 weeks. The Wechsler Adult Intelligence Scale - Revised Digit Span is used to assess auditory attention and working memory. Both forward and backward span is assessed. Both tests consist of six number sequences that the psychometrist reads aloud one at a time. After each sequence is read, the participant must repeat the digits back in the same (forward) or reverse (backward) order. Scores range from 0 to 16, with higher numbers indicate better functioning.

Mini-Mental State Exam (MMSE)baseline and 6 weeks

Change in Mini-Mental State Exam score from baseline to 6 weeks; this cognitive test estimates of dementia severity. Domains included orientation, memory, working memory, naming, following verbal and written commands, spontaneously writing a sentence, and copying two overlapping pentagons. The minimum MMSE score is 0; the maximum MMSE score is 30. Lower MMSE scores indicate more severe cognitive impairment.

Neuropsychiatric Inventory (NPI): Apathy Subscalebaseline to week 6

Change from baseline to 6 weeks in neuropsychiatric symptoms in apathy subscore. Frequency (ranges from 1=occasionally, less than once/week to 4 = very frequently, once or more/day or continuously) and severity (1=mild, 2=moderate, 3=severe) scales are scored based on responses from an informed caregiver involved in the patient's life. To obtain the NPI score, the severity score is multiplied by the frequency score. Range is 0 to 12. Larger numbers indicate more severe behavioral disturbance.

Vital Statusvital status at 6 weeks

vital status as measured by death

Electrolytes6 weeks

Percent of participants with abnormal electrolyte values at 6 weeks as assessed by local laboratory

Electrocardiogram (ECG)6 weeks

Abnormal electrocardiogram results at 6 weeks

Trial Locations

Locations (3)

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

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