Trial Outcomes & Findings for Apathy in Dementia Methylphenidate Trial 2 (NCT NCT02346201)

Last Updated: 2023-06-13

Results Overview

Mean difference in change from baseline to 6 months in the NPI apathy subscale scores as administered by certified personnel to the study caregiver. SEVERITY is graded 1 to 3 and FREQUENCY is graded 1 to 4. The overall score for the domain is the product of the severity and frequency which ranges from 1 to 12 with higher scores indicating more apathy.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

200 participants

Primary outcome timeframe

baseline to 6 months

Results posted on

2023-06-13

Participant Flow

Participant milestones

Participant milestones
Measure	Methylphenidate Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention Methylphenidate: Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention	Placebo Matching over-encapsulated placebo and psychosocial intervention Placebo: Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention
Overall Study STARTED	99	101
Overall Study COMPLETED	89	92
Overall Study NOT COMPLETED	10	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Methylphenidate Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention Methylphenidate: Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention	Placebo Matching over-encapsulated placebo and psychosocial intervention Placebo: Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention
Overall Study Adverse Event	3	2
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	6	3
Overall Study Unavailable for future follow-up	0	1
Overall Study Physician Decision	0	1
Overall Study Missed final visit	0	2

Baseline Characteristics

Apathy in Dementia Methylphenidate Trial 2

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methylphenidate n=98 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention Methylphenidate: Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention	Placebo n=101 Participants Matching over-encapsulated placebo and psychosocial intervention Placebo: Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention	Total n=199 Participants Total of all reporting groups
Age, Continuous	77 years n=5 Participants	76 years n=7 Participants	76 years n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	35 Participants n=7 Participants	68 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	66 Participants n=7 Participants	131 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	98 Participants n=5 Participants	100 Participants n=7 Participants	198 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	90 Participants n=5 Participants	91 Participants n=7 Participants	181 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaskan Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Unknown or not reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline to 6 months

Population: The number of participants with data at 6 months

Outcome measures

Outcome measures
Measure	Methylphenidate n=89 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention Methylphenidate: Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention	Placebo n=91 Participants Matching over-encapsulated placebo and psychosocial intervention Placebo: Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention
Neuropsychiatric Inventory (NPI)	-4.5 score on a scale Standard Deviation 4.1	-3.1 score on a scale Standard Deviation 3.6

PRIMARY outcome

Timeframe: Baseline to month 6

Population: The number of participants with data at 6 months

Percentage of individuals improving on Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (CGIC) from baseline to 6 months; 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. Reported data is the percentage of participants with minimal/moderate/marked improvement.

Outcome measures

Outcome measures
Measure	Methylphenidate n=89 Participants Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention Methylphenidate: Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention	Placebo n=91 Participants Matching over-encapsulated placebo and psychosocial intervention Placebo: Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention
Percentage of Participants With Change in Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (CGIC)	39 percentage of participants	32 percentage of participants

Adverse Events

Methylphenidate

Serious events: 13 serious events

Other events: 97 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Jennifer Jones, Research Coordinator

Johns Hopkins School of Public Health

Phone: 44377086812

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Methylphenidate n=99 participants at risk Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention Methylphenidate: Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention	Placebo n=101 participants at risk Matching over-encapsulated placebo and psychosocial intervention Placebo: Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention
Psychiatric disorders Hospitalization/ER visit for confusion/weakness	3.0% 3/99 • Number of events 3 • 6 months (enrollment until study completion)	0.99% 1/101 • Number of events 1 • 6 months (enrollment until study completion)
Surgical and medical procedures Hospitalization/ER visit for planned surgery	3.0% 3/99 • Number of events 3 • 6 months (enrollment until study completion)	0.00% 0/101 • 6 months (enrollment until study completion)
Infections and infestations Hospitalization/ER visit for UTI/other infection	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	3.0% 3/101 • Number of events 3 • 6 months (enrollment until study completion)
Respiratory, thoracic and mediastinal disorders Hospitalization/ER visit for Pneumonia	2.0% 2/99 • Number of events 2 • 6 months (enrollment until study completion)	0.99% 1/101 • Number of events 1 • 6 months (enrollment until study completion)
Cardiac disorders Hospitalization/ER visit for congestive heart failure or exacerbation	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	0.99% 1/101 • Number of events 2 • 6 months (enrollment until study completion)
General disorders Hospitalization/ER visit for weakness/fever	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	0.00% 0/101 • 6 months (enrollment until study completion)
Cardiac disorders Hospitalization/ER visit for atrial fibrillation	0.00% 0/99 • 6 months (enrollment until study completion)	0.99% 1/101 • Number of events 1 • 6 months (enrollment until study completion)
Musculoskeletal and connective tissue disorders Hospitalization/ER visit for upper arm and chest pain	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	0.00% 0/101 • 6 months (enrollment until study completion)
Cardiac disorders Hospitalization/ER visit for Bradycardia/nausea	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	0.00% 0/101 • 6 months (enrollment until study completion)
Vascular disorders Hospitalization/ER visit for peripheral blood clots	0.00% 0/99 • 6 months (enrollment until study completion)	0.99% 1/101 • Number of events 1 • 6 months (enrollment until study completion)
Musculoskeletal and connective tissue disorders Hospitalization/ER visit for facial drooping	0.00% 0/99 • 6 months (enrollment until study completion)	0.99% 1/101 • Number of events 1 • 6 months (enrollment until study completion)
Nervous system disorders Hospitalization/ER visit for multiple seizures	0.00% 0/99 • 6 months (enrollment until study completion)	0.99% 1/101 • Number of events 1 • 6 months (enrollment until study completion)
Gastrointestinal disorders Hospitalization/ER visit for abdominal pain and constipation	0.00% 0/99 • 6 months (enrollment until study completion)	0.99% 1/101 • Number of events 1 • 6 months (enrollment until study completion)
Gastrointestinal disorders Hospitalization/ER visit for cholecystitis	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	0.00% 0/101 • 6 months (enrollment until study completion)
Gastrointestinal disorders Hospitalization/ER visit for diarrhea	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	0.00% 0/101 • 6 months (enrollment until study completion)
General disorders Hospitalization/ER visit for gait impairment and transient visual loss	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	0.00% 0/101 • 6 months (enrollment until study completion)
Nervous system disorders Hospitalization/ER visit for syncope	1.0% 1/99 • Number of events 1 • 6 months (enrollment until study completion)	0.00% 0/101 • 6 months (enrollment until study completion)

Measure	Methylphenidate n=99 participants at risk Methylphenidate, target dose 20 mg per day (range 10-20 mg per day), in 5 mg over-capsulated tablets, and psychosocial intervention Methylphenidate: Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention	Placebo n=101 participants at risk Matching over-encapsulated placebo and psychosocial intervention Placebo: Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention
Gastrointestinal disorders Abdominal pain	17.2% 17/99 • 6 months (enrollment until study completion)	11.9% 12/101 • 6 months (enrollment until study completion)
Psychiatric disorders aggressive behavior or hostility	26.3% 26/99 • 6 months (enrollment until study completion)	26.7% 27/101 • 6 months (enrollment until study completion)
Nervous system disorders Agitation	45.5% 45/99 • 6 months (enrollment until study completion)	52.5% 53/101 • 6 months (enrollment until study completion)
Blood and lymphatic system disorders Anemia	7.1% 7/99 • 6 months (enrollment until study completion)	3.0% 3/101 • 6 months (enrollment until study completion)
Cardiac disorders angina	5.1% 5/99 • 6 months (enrollment until study completion)	5.0% 5/101 • 6 months (enrollment until study completion)
Metabolism and nutrition disorders anorexia	20.2% 20/99 • 6 months (enrollment until study completion)	15.8% 16/101 • 6 months (enrollment until study completion)
Nervous system disorders anxiety, nervousness, or tension	41.4% 41/99 • 6 months (enrollment until study completion)	51.5% 52/101 • 6 months (enrollment until study completion)
Musculoskeletal and connective tissue disorders arthralgia	40.4% 40/99 • 6 months (enrollment until study completion)	41.6% 42/101 • 6 months (enrollment until study completion)
Vascular disorders blood pressure changes	15.2% 15/99 • 6 months (enrollment until study completion)	8.9% 9/101 • 6 months (enrollment until study completion)
Eye disorders blurry vision or eyesight changes	14.1% 14/99 • 6 months (enrollment until study completion)	13.9% 14/101 • 6 months (enrollment until study completion)
Metabolism and nutrition disorders decreased appetite	32.3% 32/99 • 6 months (enrollment until study completion)	30.7% 31/101 • 6 months (enrollment until study completion)
Psychiatric disorders depressed mood	35.4% 35/99 • 6 months (enrollment until study completion)	39.6% 40/101 • 6 months (enrollment until study completion)
Social circumstances distractibility	42.4% 42/99 • 6 months (enrollment until study completion)	34.7% 35/101 • 6 months (enrollment until study completion)
Ear and labyrinth disorders dizziness	24.2% 24/99 • 6 months (enrollment until study completion)	19.8% 20/101 • 6 months (enrollment until study completion)
General disorders drowsiness	43.4% 43/99 • 6 months (enrollment until study completion)	43.6% 44/101 • 6 months (enrollment until study completion)
Gastrointestinal disorders dry mouth	22.2% 22/99 • 6 months (enrollment until study completion)	18.8% 19/101 • 6 months (enrollment until study completion)
Nervous system disorders dyskinesia	10.1% 10/99 • 6 months (enrollment until study completion)	7.9% 8/101 • 6 months (enrollment until study completion)
General disorders fever	7.1% 7/99 • 6 months (enrollment until study completion)	5.0% 5/101 • 6 months (enrollment until study completion)
Endocrine disorders hair loss	6.1% 6/99 • 6 months (enrollment until study completion)	6.9% 7/101 • 6 months (enrollment until study completion)
General disorders headache	20.2% 20/99 • 6 months (enrollment until study completion)	19.8% 20/101 • 6 months (enrollment until study completion)
Nervous system disorders hyperactivity	10.1% 10/99 • 6 months (enrollment until study completion)	6.9% 7/101 • 6 months (enrollment until study completion)
Social circumstances impaired learning	32.3% 32/99 • 6 months (enrollment until study completion)	29.7% 30/101 • 6 months (enrollment until study completion)
Social circumstances impulsivity	12.1% 12/99 • 6 months (enrollment until study completion)	20.8% 21/101 • 6 months (enrollment until study completion)
General disorders insomnia	27.3% 27/99 • 6 months (enrollment until study completion)	27.7% 28/101 • 6 months (enrollment until study completion)
General disorders libido changes	6.1% 6/99 • 6 months (enrollment until study completion)	7.9% 8/101 • 6 months (enrollment until study completion)
Gastrointestinal disorders nausea	11.1% 11/99 • 6 months (enrollment until study completion)	14.9% 15/101 • 6 months (enrollment until study completion)
Nervous system disorders numbness of fingers, toes, nose, ears, lips	13.1% 13/99 • 6 months (enrollment until study completion)	22.8% 23/101 • 6 months (enrollment until study completion)
Musculoskeletal and connective tissue disorders muscle stiffness or aching, muscle tenderness	38.4% 38/99 • 6 months (enrollment until study completion)	39.6% 40/101 • 6 months (enrollment until study completion)
Cardiac disorders palpitations	8.1% 8/99 • 6 months (enrollment until study completion)	5.0% 5/101 • 6 months (enrollment until study completion)
Skin and subcutaneous tissue disorders skin rash, redness, or inflammation	19.2% 19/99 • 6 months (enrollment until study completion)	20.8% 21/101 • 6 months (enrollment until study completion)
Cardiac disorders tachycardia (increased heart rate)	3.0% 3/99 • 6 months (enrollment until study completion)	5.9% 6/101 • 6 months (enrollment until study completion)
Renal and urinary disorders urine color changes	8.1% 8/99 • 6 months (enrollment until study completion)	6.9% 7/101 • 6 months (enrollment until study completion)
Renal and urinary disorders urine output, decreased	7.1% 7/99 • 6 months (enrollment until study completion)	6.9% 7/101 • 6 months (enrollment until study completion)
Metabolism and nutrition disorders unintentional weight loss	14.1% 14/99 • 6 months (enrollment until study completion)	7.9% 8/101 • 6 months (enrollment until study completion)
Respiratory, thoracic and mediastinal disorders cough/congestion/bronchitis	12.1% 12/99 • 6 months (enrollment until study completion)	10.9% 11/101 • 6 months (enrollment until study completion)
Gastrointestinal disorders diarrhea	10.1% 10/99 • 6 months (enrollment until study completion)	7.9% 8/101 • 6 months (enrollment until study completion)
Injury, poisoning and procedural complications falls with/without bruising	10.1% 10/99 • 6 months (enrollment until study completion)	5.9% 6/101 • 6 months (enrollment until study completion)
Vascular disorders feeling cold	0.00% 0/99 • 6 months (enrollment until study completion)	5.9% 6/101 • 6 months (enrollment until study completion)
General disorders fluid retention/swollen feet	5.1% 5/99 • 6 months (enrollment until study completion)	3.0% 3/101 • 6 months (enrollment until study completion)
Nervous system disorders irritability	4.0% 4/99 • 6 months (enrollment until study completion)	7.9% 8/101 • 6 months (enrollment until study completion)
General disorders night sweats	0.00% 0/99 • 6 months (enrollment until study completion)	5.0% 5/101 • 6 months (enrollment until study completion)
Skin and subcutaneous tissue disorders pruritis	5.1% 5/99 • 6 months (enrollment until study completion)	2.0% 2/101 • 6 months (enrollment until study completion)
Metabolism and nutrition disorders Lost more than 7% of baseline body weight	10.1% 10/99 • 6 months (enrollment until study completion)	5.9% 6/101 • 6 months (enrollment until study completion)