Methylphenidate for Apathy in Veterans With Parkinson's Disease

NCT05669170 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CX002673-01
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Apathy is one of the most common behavioral symptoms of Parkinson's disease. Patients with apathy show diminution in motivation and goal-directed behaviors, which is a fundamental aspect of human functioning, affecting dependency and quality of life. Although apathy is thought to be potentially treatable currently there are no effective treatments for apathy. Given the higher incidence of medical and psychiatric comorbidities, the Veterans Affairs health system represents a unique population for which medication response may be different from the general population. This study aims to evaluate if a medication that has already been proven to be useful in Alzheimer's disease patients with apathy, could be helpful in Parkinson's disease as well as decreasing its debilitating consequences and reducing patients' dependency on caregivers, providing well-deserved relief to patients and their loved ones.

Conditions

Parkinson Disease; Apathy

Keywords

methylphenidate; apathy; Parkinson disease

Outcome Measures

Primary Outcomes (2)

• Apathy Evaluation Scale (AES)

  This measure is an 18-item scale initially developed as a method for measuring apathy resulting from brain-related pathology.

  6 weeks

• Clinical Global Impression of Change (CGIC)

  The CGIC is a systematic method, developed for the Alzheimer's disease (AD) setting to assess clinically significant change in a clinical trial as viewed by an independent, skilled, and experienced clinician and has been used as an outcome in Parkinson disease trials

  6 weeks

Secondary Outcomes (9)

• Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog)

  6 weeks

• Continuous Performance Test (CPT)

  6 weeks

• Trail Making Test (TMT)

  6 weeks

• Neuropsychiatric Inventory (NPI)

  6 weeks

• Starkstein Apathy Scale (SAS)

  6 weeks

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Methylphenidate 20 mg

Behavioral: Psychosocial intervention; Drug: Methylphenidate

Placebo

PLACEBO COMPARATOR

Placebo

Behavioral: Psychosocial intervention

Interventions

Psychosocial intervention BEHAVIORAL

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.

Placebo; Treatment

Methylphenidate DRUG

norepinephrine and dopamine reuptake inhibitor

Treatment

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Ralph H. Johnson VA Medical Center: lead

Related Publications (5)

• 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.

  PMID: 34570180 BACKGROUND

• 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.

  PMID: 24021498 BACKGROUND

• 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.

  PMID: 30366958 BACKGROUND

• 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.

  PMID: 10486397 BACKGROUND

• 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.

  PMID: 25895932 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Lethargy

Interventions

Psychosocial Intervention; Methylphenidate

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: December 30, 2022
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 30, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share