Methylphenidate for Apathy in Veterans With Parkinson's Disease

Launched by RALPH H. JOHNSON VA MEDICAL CENTER · Dec 28, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating whether a medication called methylphenidate can help reduce apathy in veterans with Parkinson's disease. Apathy is a common problem in Parkinson's that makes people feel less motivated and less able to pursue their goals, which can significantly affect their quality of life. While there are currently no effective treatments for this specific issue, previous studies have shown that methylphenidate may help people with Alzheimer's disease who experience similar symptoms. The goal of this study is to see if it can also benefit veterans with Parkinson's, potentially easing their feelings of apathy and reducing the burden on caregivers.

To participate in the trial, participants must be veterans aged 40 or older who have been diagnosed with Parkinson's disease and have experienced significant apathy for at least four weeks. They should have a certain level of cognitive ability and must have a primary caregiver who can support them throughout the study. Participants will not be able to change their Parkinson's medications before joining the trial, and specific health conditions will disqualify some individuals. If eligible, participants can expect to receive the medication and be monitored closely by healthcare professionals to assess its effects on their apathy and overall well-being.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • • Clinically established or probable Parkinson disease according to the Movement Disorders Society Clinical Diagnostic Criteria for Parkinson's Disease
• • Age 40 or older at the time of screening
• • Montreal Cognitive Assessment (MoCA) score between 17-30.
• • Clinical Dementia Rating scale (CDR) lower than 1 and CDR sum of boxes lower than 4.5. The CDR is a numeric scale used to quantify the severity of symptoms of dementia. Using a structured interview protocol, qualified raters assess the subject's cognitive and functional performance in six areas: memory, orientation, judgement, and problem solving, community affairs, home and hobbies, and personal care. Scores are combined to obtain a composite score ranging from 0 through 3. A score between 0 and 1 indicates none or mild symptoms. The individual scores can also be added up, which gives the sum of boxes score.
• • 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'
• • Provision of informed consent for participation in the study by the patient. The ability to provide consent will be determined by the Assessment of Capacity for Everyday Decision-Making (ACED). The total score must be 9 (out of 10) or higher to meet the criteria for the study.
• • 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
• • No change to PD medications within the month preceding randomization, including starting, stopping, or dosage modifications
• • Treatment with stable doses of levodopa and cholinesterase inhibitors (ChEIs) is allowable if stable for 3 months before randomization. Other psychotropics (with the exclusion of antipsychotics), if stable for 3 months, may be allowed only with PIs' approval on a case-by-case basis
• Exclusion Criteria:
• • • Meets criteria Major Depressive Episode according to the Diagnostic Statistical Manual of Mental Disorder 5
• • History of psychotic symptoms due to another illness (i.e., schizophrenia, psychosis in mood disorders, etc.) in the past 2 years
• • 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'
• • Clinically significant impulse control disorders as assessed by the QUIP
• • Substance use disorder in the past year as assessed by the Drug Abuse Screening Test (DAST-10).
• • Treatment with psychotropic medications in the 2 weeks prior to randomization with the exception of approved treatments for cognitive impairment (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 PI approval on a case-by-case basis. Note that antipsychotics are expressly prohibited
• • Treatment with methylphenidate is contraindicated in the opinion of the PIs
• • Failure of treatment with methylphenidate in the past for apathy
• • 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
• • Active suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).60 If any of the responses to the questionnaires are yes, the subject will be evaluated by a psychiatrist to assess the risk of suicidality.
• • Uncontrolled hypertension (medication non-compliance or past 3 months with a diastolic reading of 105 mmHg)
• • Symptomatic coronary artery disease deemed to be significant by the PIs at the time of screening
• • Unintentional weight loss as determined by the PIs in the last three months
• • Significant communicative impairments that prohibit meaningful participation in the study assessments
• • Current participation in a clinical trial
• • 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
• • CNS abnormalities (e.g., cerebral aneurysm) and/or other vascular abnormalities such as vasculitis or pre-existing stroke, motor tics or family history or diagnosis of Tourette's syndrome, seizures (convulsions, epilepsy), or abnormal EEGs
• • Any condition that, in the opinion of the PIs, makes it medically inappropriate or risky for the patient to enroll in the trial
• • Women who are currently pregnant (methylphenidate is category D). Screening will include pregnancy test