Apathy in Dementia Methylphenidate Trial 2
Condition: Apathy; Alzheimer's Disease
MeSH terms: Alzheimer Disease; Dementia
Intervention: Methylphenidate; Placebo
Intervention description: Two 5mg methylphenidate over-encapsulated drug taken twice a day for 6 months (total of 20 mg methylphenidate per day), and psychosocial intervention; Two over-encapsulated placebo taken twice a day for 6 months and psychosocial intervention
Intervention MeSH terms: Methylphenidate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 200.0
Sex: All
Healthy volunteers: No

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 abnormal
             electroencephalograms

          -  Lack of appetite that results in significant unintentional weight loss as determined
             by the study physician in the last three months

          -  Uncontrolled hyperthyroidism

          -  Any cardiovascular or cerebrovascular abnormality deemed to be clinically significant
             by the study physician, tachycardia (heart rate > 100 beats per minute), or
             uncontrolled hypertension (defined as medication non-compliance or past 3 months with
             a diastolic reading > 105 mm Hg), at the time of screening

          -  Closed angle glaucoma or pheochromocytoma

          -  Women with childbearing potential

          -  Current participation in a clinical trial or study that may add significant burden or
             affect study outcomes

          -  Any condition that, in the opinion of the study physician, makes it medically
             inappropriate or risky for the potential participant to enroll in the trial,
             including, but not limited to, contraindication to treatment with methylphenidate.