Parkinson's DiseasePhase 2KPDNCT06231563
Ketamine for Veterans With Parkinson's Disease
A Phase 2 study testing Ketamine and Remimazolam in people with Parkinson's Disease, run by VA Office of Research and Development at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Ketamine and Remimazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2026to 30 Sep 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
- Moderate or severe substance use disorder during the 6 months prior to enrollment or a breathalyzer test showing an alcohol level > 0% at screening or a positive urine toxicology panel at screening. Note that a positive result for cannabis is an exception; see Inclusion Criteria
- 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
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- Current severity of depression symptoms warranting immediate treatment (i.e., resulting in inability to provide for basic needs/safety) at screening
- Meeting standard safety exclusion criteria for TMS (seizure disorder, ferrous metal or implanted devices above the chest, history of severe traumatic brain injury, tinnitus)
- Meeting standard safety exclusion criteria for ketamine treatment (previous hypersensitivity reaction to ketamine, hepatitis or liver failure, cystitis, or underlying cardiovascular conditions in which increased blood pressure would pose a risk of complications)
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121-1563
Anusha Badathala, MD, 415-688-1923, anusha.badathala@ncire.org
Rebecca Yu, (415) 221-4810 ext. 3687, rebecca.yu@va.gov
About this study
Official title: Examining Ketamine Effects on Depression, Neuroplasticity, and Inflammation in Veterans With Parkinson's Disease
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.
Read the detailed 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.
- Conditions
- Parkinson's Disease
- Being tested
- Ketamine, Remimazolam
- Keywords
- Parkinson's disease, Ketamine, Depression, Inflammatory markers, Neuroplasticity, Clinical Trial Protocol
- Medical subject headings
- Parkinson Disease, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
intravenous ketamine infusion 0.5 mg/kg
RemimazolamDrug
intravenous remimazolam infusion 0.03 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | intravenous ketamine infusion 0.5 mg/kg Receives: Drug: Ketamine |
| Remimazolam | Placebo comparator | intravenous remimazolam infusion 0.03 mg/kg Receives: Drug: Remimazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline and 24 hours post-infusion.
Secondary outcomes (13)
Montgomery-Asberg Depression Rating Scale (MADRS)
Changes in depression severity as measured by Montgomery-Asberg Depression Rating Scale scores. Overall score ranges from 0 to 60, where higher scores indicate more severe depression
Measured: Baseline to 24 hours post-infusion, Day 3, Day 5, Day 7
Hamilton Depression Rating Scale-7 (HAMD-7)
Changes in core depressive symptoms as measured by the Hamilton Depression Rating Scale-7. Overall score ranges from 0 to 56, where higher scores indicate more severe depression
Measured: Baseline to 24 hours post-infusion, Day 3, Day 5, Day 7
Patient- Reported Outcomes Measurement Information System (PROMIS®)
Changes in functional impairment related to PD as measured by the Patient- Reported Outcomes Measurement Information System (PROMIS®), where higher scores indicate more impairment
Measured: Baseline to Day 7
Quality of Life in Neurological Disorders (Neuro-QoLTM)
Changes in quality of life measured by select measures on the Quality of Life in Neurological Disorders (Neuro-QoLTM), where higher scores indicate more impairment
Measured: Baseline to Day 7
Incidence, severity, and frequency of Adverse Events (AEs) including Treatment- Emergent AEs (TEAEs) and Serious AEs (SAEs)
Incidence, severity, and frequency of Adverse Events (AEs) including Treatment- Emergent AEs (TEAEs) and Serious AEs (SAEs)
Measured: Baseline to Day 7
Ketamine Side Effect Tool (KSET)
Incidence, severity and frequency of AEs using a study-specific adaptation of the Ketamine Side Effect Tool (KSET)
Measured: Baseline to Day 7
Enhanced Scale for the Assessment of Positive Symptoms for Parkinson's Disease (eSAPS- PD)
Changes in clinician-rated psychotic symptoms assessed using the Enhanced Scale for the Assessment of Positive Symptoms for Parkinson's Disease (eSAPS- PD). Scores range from 25 to 125, where higher scores indicate more impairment
Measured: Baseline to Day 7
Frequency, Intensity, Burden of Side Effects Rating Scale (FIBSER)
Tolerability as assessed by the Frequency, Intensity, Burden of Side Effects Rating Scale (FIBSER). Scores range from 0-6, where higher scores indicate more impairment
Measured: Day 7
Hamilton Anxiety Rating Scale (HAM-A)
Changes in anxiety as measured by the Hamilton Anxiety Rating Scale (HAM-A); Overall score ranges from 0 to 56, where higher scores indicate more severe anxiety
Measured: Baseline to 24 hours post-infusion, Day3, Day 7
Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
Changes in PD symptom severity measured by the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
Measured: Baseline to 4 hours post-infusion, 24 hours post-infusion, Day 3, Day 5, Day 7
transcranial magnetic stimulation (TMS)
Changes in brain structure as measured by transcranial magnetic stimulation (TMS)
Measured: Baseline to 4 hours post-infusion
Changes in inflammatory index as measured by blood-based analysis
Changes in inflammatory index as measured by blood-based analysis
Measured: Baseline to 4 hours post-infusion
transcranial magnetic stimulation (TMS)
Changes in brain function as measured by transcranial magnetic stimulation (TMS)
Measured: Baseline to 4 hours post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2024
- Study start1 Mar 2026
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Veterans with Parkinson's disease (N=80) will be randomized to complete a single IV ketamine infusion or active placebo infusion (remimazolam).
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Ellen R Bradley, MD, Principal investigator, San Francisco VA Medical Center, San Francisco, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06231563
- Sponsor's protocol ID
- MHBC-004-23S
- Other IDs
- 23-40158, CX002606
- Acronym
- KPD
- Status last verified
- Apr 2026
- First submitted
- 9 Jan 2024
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Examining Ketamine Effects on Depression, Neuroplasticity, and Inflammation in Veterans With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT06231563
- Acronym / sponsor ID
- KPD / MHBC-004-23S
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, Ketamine, Depression, Inflammatory markers, Neuroplasticity, Clinical Trial Protocol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Mar 2026 (actual)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Sep 2029 (estimated)
- First posted
- 30 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Veterans with Parkinson's disease (N=80) will be randomized to complete a single IV ketamine infusion or active placebo infusion (remimazolam).
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: Ketamineintravenous ketamine infusion 0.5 mg/kg |
| Remimazolam | Placebo comparator | Drug: Remimazolamintravenous remimazolam infusion 0.03 mg/kg |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
- Moderate or severe substance use disorder during the 6 months prior to enrollment or a breathalyzer test showing an alcohol level > 0% at screening or a positive urine toxicology panel at screening. Note that a positive result for cannabis is an exception; see Inclusion Criteria
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamineintravenous ketamine infusion 0.5 mg/kg | Drug | Ketamine |
| Remimazolamintravenous remimazolam infusion 0.03 mg/kg | Drug | Remimazolam |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: baseline and 24 hours post-infusion.
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
13 secondary outcomes
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Baseline to 24 hours post-infusion, Day 3, Day 5, Day 7
Hamilton Depression Rating Scale-7 (HAMD-7)
Time frame: Baseline to 24 hours post-infusion, Day 3, Day 5, Day 7
Patient- Reported Outcomes Measurement Information System (PROMIS®)
Time frame: Baseline to Day 7
Quality of Life in Neurological Disorders (Neuro-QoLTM)
Time frame: Baseline to Day 7
Incidence, severity, and frequency of Adverse Events (AEs) including Treatment- Emergent AEs (TEAEs) and Serious AEs (SAEs)
Time frame: Baseline to Day 7
Ketamine Side Effect Tool (KSET)
Time frame: Baseline to Day 7
Enhanced Scale for the Assessment of Positive Symptoms for Parkinson's Disease (eSAPS- PD)
Time frame: Baseline to Day 7
Frequency, Intensity, Burden of Side Effects Rating Scale (FIBSER)
Time frame: Day 7
Hamilton Anxiety Rating Scale (HAM-A)
Time frame: Baseline to 24 hours post-infusion, Day3, Day 7
Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
Time frame: Baseline to 4 hours post-infusion, 24 hours post-infusion, Day 3, Day 5, Day 7
transcranial magnetic stimulation (TMS)
Time frame: Baseline to 4 hours post-infusion
Changes in inflammatory index as measured by blood-based analysis
Time frame: Baseline to 4 hours post-infusion
transcranial magnetic stimulation (TMS)
Time frame: Baseline to 4 hours post-infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ellen R Bradley, MD principal investigator
San Francisco VA Medical Center, San Francisco, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine and Remimazolam in people with Parkinson's Disease, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ellen R Bradley, MD ((415) 221-4810 ext. 22071, ellen.bradley3@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: baseline and 24 hours post-infusion.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.