Methylphenidate for Apathy in Veterans With Parkinson's Disease
NCT ID: NCT05669170
Last Updated: 2022-12-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE2
60 participants
INTERVENTIONAL
2024-01-31
2028-06-30
Brief Summary
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Detailed Description
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Despite the high prevalence of apathy in PD and its serious consequences, there are no proven treatments for this condition. Dopaminergic enhancement appears as a potential mechanism as there is evidence that degeneration of the frontostriatal circuits involving the prefrontal cortex is one of the main mechanisms for the presence of apathy in PD as well as other neurodegenerative disorders, such as Alzheimer's disease (AD). This degeneration is associated with deficits in dopaminergic and noradrenergic input fibers to the prefrontal cortex.
Methylphenidate, a dopamine and noradrenaline reuptake inhibitor, has been shown to be safe and effective in PD in the treatment of motor and cognitive symptoms, and several small trials and case series reported improvement in motivation and mood. Recently, methylphenidate was shown to be safe and improve apathy in AD in a series of well-controlled studies conducted by members of our team. This represents a relevant result as similar pathophysiology for apathy has been suggested in both AD and PD.
Given the common biological pathways in the onset of apathy in both disorders, we propose that, as is the case in AD, methylphenidate will be a safe and effective treatment for apathy in PD.
The goal of the proposed study of Methylphenidate for Apathy in Veterans with Parkinson's Disease (MAV-PD) is to expand upon this encouraging preliminary work by evaluating methylphenidate for the treatment of apathy in PD Veteran patients. It is our strong belief that a trial designed specifically in Veteran population should be conducted, as reliance on data from civilian populations who differ in their level of medical and psychiatric comorbidity, which influence drug response, may not be applicable to Veterans with PD.
This study will employ a single-site, parallel, randomized, double-blind, placebo-controlled design conducted on 60 Veterans with apathy and PD. MAV-PD is designed specifically for PD patients with apathy, and as such it employs a concise battery of neuropsychological tests that have been chosen for this patient group.
This project is of great importance because it will explore the efficacy and safety of a promising dopamine agonist for treating apathy in PD, where there are no proven treatment options. Should methylphenidate be found effective, it will likely become the first-line therapy for apathy in PD.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Treatment
Methylphenidate 20 mg
Psychosocial intervention
The counseling session, in which a trained study clinician will counsel the primary caregiver, will take place at each study visit and after the randomization visit. It will last approximately 20-30 minutes. Each counseling session will consist of the following elements:
* Review and adjustment of the patient and caregiver supportive care plans
* Emotional support and the opportunity to ventilate feelings
* Counseling regarding specific caregiving skills
* Assistance with problem-solving of specific issues that the caregiver brings to the sessions
* Answers to questions regarding the educational materials The educational materials will consist of a copy of the book "The 36-Hour Day" by Nancy L. Mace and Peter V. Rabins. The caregiver also will be provided with 24-hour phone access to the study nurse or physician for assistance with crises that may arise after hours.
Methylphenidate
norepinephrine and dopamine reuptake inhibitor
Placebo
Placebo
Psychosocial intervention
The counseling session, in which a trained study clinician will counsel the primary caregiver, will take place at each study visit and after the randomization visit. It will last approximately 20-30 minutes. Each counseling session will consist of the following elements:
* Review and adjustment of the patient and caregiver supportive care plans
* Emotional support and the opportunity to ventilate feelings
* Counseling regarding specific caregiving skills
* Assistance with problem-solving of specific issues that the caregiver brings to the sessions
* Answers to questions regarding the educational materials The educational materials will consist of a copy of the book "The 36-Hour Day" by Nancy L. Mace and Peter V. Rabins. The caregiver also will be provided with 24-hour phone access to the study nurse or physician for assistance with crises that may arise after hours.
Interventions
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Psychosocial intervention
The counseling session, in which a trained study clinician will counsel the primary caregiver, will take place at each study visit and after the randomization visit. It will last approximately 20-30 minutes. Each counseling session will consist of the following elements:
* Review and adjustment of the patient and caregiver supportive care plans
* Emotional support and the opportunity to ventilate feelings
* Counseling regarding specific caregiving skills
* Assistance with problem-solving of specific issues that the caregiver brings to the sessions
* Answers to questions regarding the educational materials The educational materials will consist of a copy of the book "The 36-Hour Day" by Nancy L. Mace and Peter V. Rabins. The caregiver also will be provided with 24-hour phone access to the study nurse or physician for assistance with crises that may arise after hours.
Methylphenidate
norepinephrine and dopamine reuptake inhibitor
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
40 Years
ALL
No
Sponsors
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Ralph H. Johnson VA Medical Center
FED
Responsible Party
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Olga Brawman-mintzer
Staff Physician
References
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Mintzer J, Lanctot KL, Scherer RW, Rosenberg PB, Herrmann N, van Dyck CH, Padala PR, Brawman-Mintzer O, Porsteinsson AP, Lerner AJ, Craft S, Levey AI, Burke W, Perin J, Shade D; ADMET 2 Research Group. Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial. JAMA Neurol. 2021 Nov 1;78(11):1324-1332. doi: 10.1001/jamaneurol.2021.3356.
Rosenberg PB, Lanctot KL, Drye LT, Herrmann N, Scherer RW, Bachman DL, Mintzer JE, ADMET Investigators. Safety and efficacy of methylphenidate for apathy in Alzheimer's disease: a randomized, placebo-controlled trial. J Clin Psychiatry. 2013 Aug;74(8):810-6. doi: 10.4088/JCP.12m08099.
Le Heron C, Holroyd CB, Salamone J, Husain M. Brain mechanisms underlying apathy. J Neurol Neurosurg Psychiatry. 2019 Mar;90(3):302-312. doi: 10.1136/jnnp-2018-318265. Epub 2018 Oct 26.
Aarsland D, Larsen JP, Lim NG, Janvin C, Karlsen K, Tandberg E, Cummings JL. Range of neuropsychiatric disturbances in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999 Oct;67(4):492-6. doi: 10.1136/jnnp.67.4.492.
Pagonabarraga J, Kulisevsky J, Strafella AP, Krack P. Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment. Lancet Neurol. 2015 May;14(5):518-31. doi: 10.1016/S1474-4422(15)00019-8. Epub 2015 Apr 12.
Other Identifiers
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CX002673-01
Identifier Type: -
Identifier Source: org_study_id