Trial Outcomes & Findings for Apathy in Dementia Methylphenidate Trial (ADMET) (NCT NCT01117181)

NCT ID: NCT01117181

Last Updated: 2018-06-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 60 participants
• Primary outcome timeframe: baseline to 6 weeks
• Results posted on: 2018-06-12

Participant Flow

Clinical center recruited from established outpatient clinics, from living facilities, by local physicians, and from targeted advertisements in local media. The recruitment period started June 2010 and ended October 2011.

Participant milestones

Measure	Methylphenidate Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention	Placebo matching placebo and psychosocial intervention
Overall Study STARTED	29	31
Overall Study COMPLETED	28	29
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Methylphenidate Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention	Placebo matching placebo and psychosocial intervention
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Apathy in Dementia Methylphenidate Trial (ADMET)

Baseline characteristics by cohort

Measure	Methylphenidate n=29 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention	Placebo n=31 Participants matching placebo and psychosocial intervention	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Age, Continuous	78 years STANDARD_DEVIATION 8 • n=5 Participants	75 years STANDARD_DEVIATION 9 • n=7 Participants	76 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	20 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	21 participants n=7 Participants	41 participants n=5 Participants
Region of Enrollment Canada	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Methylphenidate n=29 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), and psychosocial intervention	Placebo n=31 Participants Placebo and psychosocial intervention
Apathy Evaluation Scale (AES)	-1.9 units on a scale Standard Error 1.5	0.6 units on a scale Standard Error 1.4

PRIMARY outcome

Timeframe: baseline 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.

Outcome measures

Measure	Methylphenidate n=29 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), and psychosocial intervention	Placebo n=31 Participants Placebo and psychosocial intervention
Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change	21 percentage of participants who improve	3 percentage of participants who improve

SECONDARY outcome

Timeframe: baseline 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.

Outcome measures

Measure	Methylphenidate n=26 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), and psychosocial intervention	Placebo n=29 Participants Placebo and psychosocial intervention
Digit Span	0.46 units on a scale Standard Deviation 1.55	-0.07 units on a scale Standard Deviation 1.25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Methylphenidate n=29 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), and psychosocial intervention	Placebo n=31 Participants Placebo and psychosocial intervention
Mini-Mental State Exam (MMSE)	1.3 units on a scale Standard Error 0.6	-0.3 units on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: baseline 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.

Outcome measures

Measure	Methylphenidate n=29 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), and psychosocial intervention	Placebo n=31 Participants Placebo and psychosocial intervention
Neuropsychiatric Inventory (NPI): Apathy Subscale	-4.4 units on a scale Standard Error 0.6	-2.6 units on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: vital status at 6 weeks

vital status as measured by death

Outcome measures

Measure	Methylphenidate n=29 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), and psychosocial intervention	Placebo n=31 Participants Placebo and psychosocial intervention
Vital Status	0 participants who died	0 participants who died

SECONDARY outcome

Timeframe: 6 weeks

Population: One patient in the active group completed all visit 6 assessments except for the blood collection for the electrolyte sample. This patient refused this procedure.

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

Outcome measures

Measure	Methylphenidate n=27 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), and psychosocial intervention	Placebo n=29 Participants Placebo and psychosocial intervention
Electrolytes Sodium	3.70 percentage of participants	0 percentage of participants
Electrolytes Potassium	14.81 percentage of participants	10.34 percentage of participants
Electrolytes Chloride	7.41 percentage of participants	10.34 percentage of participants
Electrolytes Bicarbonate	7.41 percentage of participants	10.34 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks

Abnormal electrocardiogram results at 6 weeks

Outcome measures

Measure	Methylphenidate n=29 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), and psychosocial intervention	Placebo n=31 Participants Placebo and psychosocial intervention
Electrocardiogram (ECG)	20 participants with abnormal ECG	15 participants with abnormal ECG

Adverse Events

Methylphenidate

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Methylphenidate n=29 participants at risk Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention	Placebo n=31 participants at risk matching placebo and psychosocial intervention
Gastrointestinal disorders abdominal pain	3.4% 1/29 • Number of events 1 • treatment period (i.e., 6 weeks)	0.00% 0/31 • treatment period (i.e., 6 weeks)
Blood and lymphatic system disorders drop in hemoglobin	0.00% 0/29 • treatment period (i.e., 6 weeks)	3.2% 1/31 • Number of events 1 • treatment period (i.e., 6 weeks)

Other adverse events

Measure	Methylphenidate n=29 participants at risk Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention	Placebo n=31 participants at risk matching placebo and psychosocial intervention
Nervous system disorders agitation	58.6% 17/29 • treatment period (i.e., 6 weeks)	44.8% 13/29 • treatment period (i.e., 6 weeks)
Nervous system disorders Anxiety	58.6% 17/29 • treatment period (i.e., 6 weeks)	34.5% 10/29 • treatment period (i.e., 6 weeks)
Metabolism and nutrition disorders weight loss	34.5% 10/29 • treatment period (i.e., 6 weeks)	13.8% 4/29 • treatment period (i.e., 6 weeks)
Gastrointestinal disorders abdominal pain	20.7% 6/29 • treatment period (i.e., 6 weeks)	13.8% 4/29 • treatment period (i.e., 6 weeks)
Psychiatric disorders Aggressive behavior or hostility	31.0% 9/29 • treatment period (i.e., 6 weeks)	17.2% 5/29 • treatment period (i.e., 6 weeks)
Cardiac disorders Angina	6.9% 2/29 • treatment period (i.e., 6 weeks)	3.4% 1/29 • treatment period (i.e., 6 weeks)
Metabolism and nutrition disorders Anorexia	20.7% 6/29 • treatment period (i.e., 6 weeks)	17.2% 5/29 • treatment period (i.e., 6 weeks)
Musculoskeletal and connective tissue disorders Arthralgia	20.7% 6/29 • treatment period (i.e., 6 weeks)	48.3% 14/29 • treatment period (i.e., 6 weeks)
Vascular disorders Blood pressure changes	13.8% 4/29 • treatment period (i.e., 6 weeks)	10.3% 3/29 • treatment period (i.e., 6 weeks)
Eye disorders Blurry vision or eyesight changes	0.00% 0/29 • treatment period (i.e., 6 weeks)	10.3% 3/29 • treatment period (i.e., 6 weeks)
Metabolism and nutrition disorders Depressed appetite	27.6% 8/29 • treatment period (i.e., 6 weeks)	24.1% 7/29 • treatment period (i.e., 6 weeks)
Psychiatric disorders Depressed mood	41.4% 12/29 • treatment period (i.e., 6 weeks)	41.4% 12/29 • treatment period (i.e., 6 weeks)
Social circumstances Distractibility	37.9% 11/29 • treatment period (i.e., 6 weeks)	27.6% 8/29 • treatment period (i.e., 6 weeks)
Ear and labyrinth disorders Dizziness	37.9% 11/29 • treatment period (i.e., 6 weeks)	24.1% 7/29 • treatment period (i.e., 6 weeks)
General disorders Drowsiness	34.5% 10/29 • treatment period (i.e., 6 weeks)	44.8% 13/29 • treatment period (i.e., 6 weeks)
Gastrointestinal disorders Dry mouth	24.1% 7/29 • treatment period (i.e., 6 weeks)	20.7% 6/29 • treatment period (i.e., 6 weeks)
Nervous system disorders Dyskinesia	3.4% 1/29 • treatment period (i.e., 6 weeks)	13.8% 4/29 • treatment period (i.e., 6 weeks)
Endocrine disorders Hair loss	6.9% 2/29 • treatment period (i.e., 6 weeks)	3.4% 1/29 • treatment period (i.e., 6 weeks)
General disorders Headache	17.2% 5/29 • treatment period (i.e., 6 weeks)	13.8% 4/29 • treatment period (i.e., 6 weeks)
Nervous system disorders Hyperactivity	17.2% 5/29 • treatment period (i.e., 6 weeks)	3.4% 1/29 • treatment period (i.e., 6 weeks)
Social circumstances Impaired learning	13.8% 4/29 • treatment period (i.e., 6 weeks)	24.1% 7/29 • treatment period (i.e., 6 weeks)
Gastrointestinal disorders Nausea	10.3% 3/29 • treatment period (i.e., 6 weeks)	24.1% 7/29 • treatment period (i.e., 6 weeks)
Skin and subcutaneous tissue disorders Skin rash, redness, or inflammation	20.7% 6/29 • treatment period (i.e., 6 weeks)	20.7% 6/29 • treatment period (i.e., 6 weeks)
Nervous system disorders Tics (motor or verbal)	0.00% 0/29 • treatment period (i.e., 6 weeks)	13.8% 4/29 • treatment period (i.e., 6 weeks)

Additional Information

Anne Casper, MA

Johns Hopkins

Phone: 410-955-8183

Email: ashankli@jhsph.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place