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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG033032-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
| Medical University of South Carolina | OTHER |
| Johns Hopkins University | OTHER |
| University of Toronto |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methylphenidate | Experimental | Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention |
|
| Placebo | Placebo Comparator | matching placebo and psychosocial intervention |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Digit Span | 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. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Baltimore | Maryland | 21224 | United States | ||
| Medical University of South Carolina |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24021498 | Derived | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Methylphenidate | Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention |
| FG001 | Placebo | matching placebo and psychosocial intervention |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Methylphenidate | Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention |
| BG001 | Placebo | matching placebo and psychosocial intervention |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Error | units on a scale | baseline to 6 weeks |
|
treatment period (i.e., 6 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Methylphenidate | Methylphenidate, target dose 20 mg per day (range 10-20 mg per day) and psychosocial intervention |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| agitation | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anne Casper, MA | Johns Hopkins | 410-955-8183 | ashankli@jhsph.edu |
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| ID | Term |
|---|---|
| D053609 | Lethargy |
| D000544 | Alzheimer Disease |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D008774 | Methylphenidate |
| D000083626 | Psychosocial Intervention |
| ID | Term |
|---|---|
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| OTHER |
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|
|
| 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. |
|
|
| 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:
The educational materials will consist of a copy of the book The 36-Hour Day |
|
| baseline and 6 weeks |
| Mini-Mental State Exam (MMSE) | 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. | baseline and 6 weeks |
| Neuropsychiatric Inventory (NPI): Apathy Subscale | 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. | baseline to week 6 |
| Vital Status | vital status as measured by death | vital status at 6 weeks |
| Electrolytes | Percent of participants with abnormal electrolyte values at 6 weeks as assessed by local laboratory | 6 weeks |
| Electrocardiogram (ECG) | Abnormal electrocardiogram results at 6 weeks | 6 weeks |
| Charleston |
| South Carolina |
| 29406 |
| United States |
| Sunnybrook Health Sciences Centre | Toronto | Ontario | Canada |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Primary | 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. | Posted | Number | percentage of participants who improve | baseline to 6 weeks |
|
|
|
| Secondary | Digit Span | 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. | Posted | Mean | Standard Deviation | units on a scale | baseline and 6 weeks |
|
|
|
| Secondary | Mini-Mental State Exam (MMSE) | 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. | Posted | Mean | Standard Error | units on a scale | baseline and 6 weeks |
|
|
|
| Secondary | Neuropsychiatric Inventory (NPI): Apathy Subscale | 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. | Posted | Mean | Standard Error | units on a scale | baseline to week 6 |
|
|
|
| Secondary | Vital Status | vital status as measured by death | Posted | Number | participants who died | vital status at 6 weeks |
|
|
|
| Secondary | Electrolytes | Percent of participants with abnormal electrolyte values at 6 weeks as assessed by local laboratory | 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. | Posted | Number | percentage of participants | 6 weeks |
|
|
|
| Secondary | Electrocardiogram (ECG) | Abnormal electrocardiogram results at 6 weeks | Posted | Number | participants with abnormal ECG | 6 weeks |
|
|
|
| 1 |
| 29 |
| 29 |
| 29 |
| EG001 | Placebo | matching placebo and psychosocial intervention | 1 | 31 | 29 | 31 |
| drop in hemoglobin | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Anxiety | Nervous system disorders | Systematic Assessment |
|
| weight loss | Metabolism and nutrition disorders | Systematic Assessment | greater than 2% at week 6 |
|
| abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Aggressive behavior or hostility | Psychiatric disorders | Systematic Assessment |
|
| Angina | Cardiac disorders | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Blood pressure changes | Vascular disorders | Systematic Assessment |
|
| Blurry vision or eyesight changes | Eye disorders | Systematic Assessment |
|
| Depressed appetite | Metabolism and nutrition disorders | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | Systematic Assessment |
|
| Distractibility | Social circumstances | Systematic Assessment |
|
| Dizziness | Ear and labyrinth disorders | Systematic Assessment |
|
| Drowsiness | General disorders | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
|
| Dyskinesia | Nervous system disorders | Systematic Assessment |
|
| Hair loss | Endocrine disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Hyperactivity | Nervous system disorders | Systematic Assessment |
|
| Impaired learning | Social circumstances | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Skin rash, redness, or inflammation | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Tics (motor or verbal) | Nervous system disorders | Systematic Assessment |
|
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| D013568 | Pathological Conditions, Signs and Symptoms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D010880 |
| Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
| Chloride |
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| Bicarbonate |
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