Apathy in Dementia Methylphenidate Trial (ADMET)
Condition: Apathy; Alzheimer's Disease
MeSH terms: Alzheimer Disease; Dementia
Intervention: Methylphenidate; placebo; Psychosocial intervention
Intervention description: 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.; 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.; 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:
Review and adjustment of the patient and caregiver supportive care plans
Emotional support and opportunity to ventilate feelings
Counseling regarding specific caregiving skills
Assistance with problem solving of specific issues that the caregiver brings to the sessions
Answers for questions regarding the educational materials
The educational materials will consist of a copy of the book The 36-Hour Day
Intervention MeSH terms: Methylphenidate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Alzheimer's disease; Apathy; Methylphenidate; Dopaminergic agents; Apathy Evaluation Scale; Dementia

Summary:

      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.
    

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
             10-26 inclusive; MMSE scores above 26 in those who nevertheless meet criteria for AD
             may be allowed with Steering Committee approval on a case by case basis

          -  Clinically significant apathy for at least four weeks for which either 1) the
             frequency of apathy as assessed by the Neuropsychiatric Inventory (NPI) is 'Very
             frequently', or 2) 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 patient or surrogate
             (if the patient is unable to provide informed consent) and caregiver

          -  Availability of primary caregiver, who spends greater than ten hours a week with the
             patient and supervises his/her care, to accompany the patient to study visits and to
             participate in the study

          -  Sufficient fluency, of both the patient and caregiver, in written and spoken English
             to participate in study visits, physical exams, and outcome assessments

          -  No change to AD medications within the month preceding randomization, including
             starting, stopping, or dosage modifications

          -  Treatment with stable doses of selective serotonin reuptake inhibitor
             antidepressants(SSRIs) is appropriate if stable for 3 months prior to randomization.
             Other psychotropics(with the exclusion of antipsychotics), if stable for 3 months, may
             be allowed only with Steering Committee approval on a case by case basis.

        Exclusion criteria:

          -  Meets criteria for Major Depressive Episode, by Diagnostic Statistical Manual of
             Mental Disorder - IV (TR) criteria

          -  Clinically significant agitation /aggression for which either 1) the frequency of
             agitation /aggression as assessed by the NPI is 'Very frequently', or 2) 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 1) the frequency of delusions as
             assessed by the NPI is 'Very frequently', or 2) 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 1) the frequency of
             hallucinations as assessed by the NPI is 'Very frequently', or 2) 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'

          -  Treatment with psychotropic medications in the 2 weeks prior to randomization with the
             exception of approved treatments for dementia (ChEIs and memantine), selective
             serotonin reuptake inhibitor antidepressants, and trazodone (if used as an aid to
             facilitate sleep and not as an antidepressant); other psychotropics (with the
             exclusion of antipsychotics), if stable for 3 months, may be allowed only with
             Steering Committee approval on a case by case basis. Note that antipsychotics are
             expressly prohibited.

          -  Treatment with methylphenidate is contraindicated in the opinion of the study
             physician

          -  Failure of treatment with methylphenidate in the past for apathy after convincing
             evidence of an adequate trial as judged by study physician

          -  Treatment with a medication that would prohibit the safe concurrent use of
             methylphenidate such as monoamine oxidase inhibitors and tricyclic antidepressants

          -  Need for acute psychiatric hospitalization or is suicidal

          -  Uncontrolled hypertension (medication non-compliance or past 3 months with a diastolic
             reading of 105 as verified by compartment pressure of the rectus sheath (CPRS))

          -  Symptomatic coronary artery disease deemed to be significant by study physician at the
             time of screening

          -  Lack of appetite that results in significant unintentional weight loss as determined
             by the study physician in the last three months

          -  Significant communicative impairments

          -  Current participation in a clinical trial or in any study that may add significant
             burden or affect study outcomes

          -  Hyperthyroidism, advanced arteriosclerosis, symptomatic cardiovascular disease,
             serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm
             abnormalities, or a family history of sudden death or death related to heart problems

          -  Glaucoma, pheochromocytoma, or known or suspected hypersensitivity to methylphenidate
             or its excipients

          -  Central Nervous System (CNS) abnormalities (e.g., cerebral aneurysm) and/or other
             vascular abnormalities such as vasculitis or pre-existing stroke, motor tics or a
             family history or diagnosis of Tourette's syndrome, seizures (convulsions, epilepsy),
             or abnormal EEGs

          -  Any condition that, in the opinion of the study physician, makes it medically
             inappropriate or risky for the patient to enroll in the trial