Ketamine for Veterans With Parkinson's Disease

NCT06231563 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: MHBC-004-23S23-40158CX002606
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Parkinson's disease (PD) is a devastating illness that has a growing impact on Veterans. One of the most disabling symptoms is depression, which is common in PD and linked to poor quality of life and higher risk of suicide. Unfortunately, there is a lack of effective treatments for depression in PD. Ketamine, which has rapid and potent antidepressant effects, is a potential option but has not been tested in Veterans with PD. Studies in rodents show that ketamine may not only improve depression in PD, it may target two of the underlying drivers of the disease: (1) reduced neuroplasticity, or the brain's ability to adapt and remodel itself; and (2) elevated inflammation. The investigators are conducting a randomized, placebo-controlled study to examine if a dose of intravenous (IV) ketamine improves depression in Veterans with PD. The investigators will also examine ketamine's effects on neuroplasticity and inflammation, which will help us understand how ketamine works in PD and if it can be a useful treatment for Veterans with the disease. This study will lay groundwork for a larger clinical trial across multiple VA sites.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Ketamine; Depression; Inflammatory markers; Neuroplasticity; Clinical Trial Protocol

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Changes in depression as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) between baseline and 24 hours post-infusion. Overall score ranges from 0 to 60, where higher scores indicate more severe depression

  baseline and 24 hours post-infusion.

Secondary Outcomes (13)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Baseline to 24 hours post-infusion, Day 3, Day 5, Day 7

• Hamilton Depression Rating Scale-7 (HAMD-7)

  Baseline to 24 hours post-infusion, Day 3, Day 5, Day 7

• Patient- Reported Outcomes Measurement Information System (PROMIS®)

  Baseline to Day 7

• Quality of Life in Neurological Disorders (Neuro-QoLTM)

  Baseline to Day 7

• Incidence, severity, and frequency of Adverse Events (AEs) including Treatment- Emergent AEs (TEAEs) and Serious AEs (SAEs)

  Baseline to Day 7

Study Arms (2)

Ketamine

EXPERIMENTAL

intravenous ketamine infusion 0.5 mg/kg

Drug: Ketamine

Remimazolam

PLACEBO COMPARATOR

intravenous remimazolam infusion 0.03 mg/kg

Drug: Remimazolam

Interventions

Ketamine DRUG

intravenous ketamine infusion 0.5 mg/kg

Ketamine

Remimazolam DRUG

intravenous remimazolam infusion 0.03 mg/kg

Remimazolam

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and provide written informed consent.
• Is a United States Veteran.
• Between 40-80 years old at the time of informed consent
• Have neurologist-diagnosed idiopathic Parkinson's disease (PD) for at least six months prior to enrollment
• History of inadequate response to at least one trial of antidepressant medication
• On a stable regimen of all medications for at least 2 months prior to enrollment and have no planned medication changes during the period of active participation.
• Commit to attend all in-person and remote study visits and participate in all data collection procedures.
• Have a score \>/=20 on the Montgomery-Asberg Depression Rating Scale (MADRS), consistent with moderate or greater depressive symptom severity, at Baseline.
• If already engaged in psychotherapy or other non-pharmacologic treatments for depression, agree to maintain consistent engagement throughout the period of active study participation.
• If not engaged in psychotherapy or other non-pharmacologic treatments for depression, agree to avoid starting a new course of treatment for the period of active study participation.
• Agree to abstain from cannabis for a minimum of 72 hours prior to assessments on Day - 1 and to remain abstinent through assessments on Day 0
• If a regular user of tobacco or nicotine, agree to maintain a consistent pattern of use throughout the period of active study participation; if an infrequent/occasional user, agree to abstain throughout the period of active study participation
• For people who can become pregnant or trying to conceive: agree to use highly effective contraception from entry into the trial through Day 7 assessments

You may not qualify if:

• Lifetime history of schizophrenia or schizoaffective disorder or bipolar disorder or current psychosis with loss of insight
• Dementia or cognitive impairment as determined by a MoCA (telephone version) score \<18 at screening.
• Pregnancy, breastfeeding, or plans to become pregnant during the period of trial participation.
• Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) treatment within 30 days prior to enrollment or plans to begin either therapy during the participation period
• High risk of self-harm/suicide that warrants immediate treatment as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening
• Current severity of depression symptoms warranting immediate treatment (i.e., resulting in inability to provide for basic needs/safety) at screening
• Concomitant medications that may interfere with ketamine treatment or increase risk of adverse events (e.g., benzodiazepines, sedative-hypnotics, lamotrigine, MAOIs) if it is not medically appropriate or feasible for the participant to abstain from use for at least 5 half-lives prior to assessments on Day -1 and remain abstinent through assessments on Day 0
• Concomitant medications that may impact motor cortex plasticity (e.g., memantine, dextromethorphan) if it is not medically appropriate or feasible for the participant to abstain from use for at least 5 half-lives prior to assessments on Day -1 and remain abstinent through assessments on Day 0
• Concomitant medications that may increase risk of adverse events with TMS (i.e,. those that can lower the seizure threshold) if it is not medically appropriate or feasible for the participant to abstain from use for at least 5 half-lives prior to assessments on Day -1 and remain abstinent through assessments on Day 0
• Autoimmune disorders (e.g., multiple sclerosis, lupus, rheumatoid arthritis) or neoplastic disorders
• Use of cytokine antagonists or other medications that may modulate inflammation unless regimen has been stable for at least 2 months and there is no plan to alter the regimen during trial participation
• Another medical condition or diagnosis, physical exam finding, or laboratory abnormality that precludes participation in study procedures due to safety concerns.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, 94121-1563, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Depression

Interventions

Ketamine; remimazolam

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Ellen R Bradley, MD

  San Francisco VA Medical Center, San Francisco, CA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ellen R Bradley, MD

CONTACT

(415) 221-4810; ellen.bradley3@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-masked, active placebo-controlled, single dose randomized trial of intravenous (IV) ketamine for depression in people with Parkinson's disease (PD).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Veterans with Parkinson's disease (N=80) will be randomized to complete a single IV ketamine infusion or active placebo infusion (remimazolam).

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 30, 2024
• Study Start: March 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)