Phase 3
N=200
Apathy in Dementia Methylphenidate Trial 2
Apathy · Alzheimer's Disease
Bottom Line
View on ClinicalTrials.gov: NCT02346201 ↗Enrolled (actual)
200
Serious AEs
11.0%
Results posted
Jun 2023
Primary outcome: Primary: Neuropsychiatric Inventory (NPI) — -4.5; -3.1 score on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Methylphenidate (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Johns Hopkins Bloomberg School of Public Health
- Primary completion
- Jul 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Neuropsychiatric Inventory (NPI) |
-4.5; -3.1 | — |
| PRIMARY Percentage of Participants With Change in Modified Alzheimer's Disease Cooperative Study- Clinical Global Impression of Change (CGIC) |
39; 32 | — |
Summary
Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is a Phase III, placebo-controlled, masked, 6 month, multi-center randomized clinical trial sponsored by National Institutes of Aging involving 200 participants with Alzheimer's disease (AD). ADMET 2 is designed to examine the efficacy and safety of methylphenidate as treatment for clinically significant apathy in AD participants. ADMET 2 will enroll participants from real world settings such as outpatient, nursing home, and assisted living facilities and will examine the effects of methylphenidate on apathy and cognition. ADMET 2 will also conduct careful safety monitoring.
Eligibility Criteria
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 10-28 inclusive
- Clinically significant apathy for at least four weeks for which either
- the frequency of apathy as assessed by the Neuropsychiatric Inventory (NPI) is 'Very frequently', or
- 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 potential participant or surrogate (with participant assent if the potential participant is unable to provide informed consent) and caregiver
- Availability of primary caregiver, who spends greater than ten hours a week with the potential participant and supervises his/her care, to accompany the potential participant to study visits and to participate in the study
- Sufficient fluency, of both the potential participant and caregiver, in written and spoken English to participate in study visits, physical exams, and outcome assessments
- If female, woman must be post-menopausal for at least 2 years or have had a hysterectomy
Exclusion criteria
- Currently meets criteria for Major Depressive Episode, by Diagnostic Statistical Manual of Mental Disorder - IV (TR) criteria
- Clinically significant agitation /aggression for which either
- the frequency of agitation /aggression as assessed by the NPI is 'Very frequently', or
- 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
- the frequency of delusions as assessed by the NPI is 'Very frequently', or
- 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
- the frequency of hallucinations as assessed by the NPI is 'Very frequently', or
- 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'
- Change to AD medications within the month preceding randomization, including starting, stopping, or dosage modifications
- Change in anti-depressant (except for trazodone used for sleeping difficulties as described below) use within the 30 days preceding randomization or a period of time equal to 5 half-lives of drug, whichever period of time is longer
- Use of trazodone > 50mg or lorazepam > 0.5mg or for indications other than sleeping difficulties within the 30 days preceding randomization or a period of time equal to 5 half-lives of drug, whichever period of time is longer. Other benzodiazepines are prohibited in the past 30 days or within 5 half-lives, whichever period of time is longer.
- Failure of treatment with methylphenidate in the past for apathy after convincing evidence of an adequate trial as judged by study physician
- Currently taking any amphetamine product, an antipsychotic, bupropion, or any medication that would prohibit the safe concurrent use of methylphenidate, including but not limited to monoamine oxidase inhibitors and tricyclic antidepressants within the 30 days preceding randomization or a period of time equal to 5 half-lives of drug, whichever period of time is longer
- Need for acute psychiatric hospitalization or is suicidal in the opinion of the study physician
- Significant communicative impairments that would affect participation in clinical trial
- Central nervous system abnormalities (e.g., cerebral aneurysm), seizures (convulsions, epilepsy), Tourette's syndrome or presence of motor tics, or abnorma
Data sourced from ClinicalTrials.gov (NCT02346201). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.