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Clinical Trial 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.


Clinical Trial Description

This is a double-masked, active placebo-controlled, single dose randomized trial of intravenous (IV) ketamine versus remimazolam for depression in Veterans (N=80) with Parkinson's disease (PD). The investigators hypothesize that ketamine will have a strong safety and tolerability profile and improve depressive symptoms within 24 hours (Aim 1). Further, its antidepressant effects will be associated with modulation of both impaired neuroplasticity (Aim 2) and elevated inflammatory activity (Aim 3). To test these hypotheses, the investigators will use clinical assessments (of adverse events, tolerability, and depression), non-invasive brain stimulation techniques to quantify changes in LTP-like neuroplasticity, and blood-based cytokine measurement to quantify changes in systemic inflammation. This study will provide clinical efficacy data and elucidate ketamine's mechanisms of action in PD using accessible, neuroscience-informed markers of neuroplasticity and inflammation. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT06231563
Study type Interventional
Source VA Office of Research and Development
Contact Ellen R Bradley, MD
Phone (415) 221-4810
Email ellen.bradley3@va.gov
Status Not yet recruiting
Phase Phase 2
Start date July 1, 2024
Completion date June 30, 2029