Parkinson's DiseasePhase 2KET-PDNCT04944017
Ketamine for the Treatment of Depression in Parkinson's Disease
A Phase 2 study testing Ketamine Infusion in people with Parkinson's Disease and Depression, run by Yale University at 1 site in United States.
Trial summary
The main purpose of this study is to examine the efficacy and safety of a repeated dosing ketamine infusion paradigm compared to placebo in individuals with PD. A subset of participants in each arm will undergo baseline and post-treatment PET and fMRI scans, to examine whether changes in synaptic density and… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Parkinson's Disease, Depression
- What is being tested?
- Ketamine Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Nov 2021to 24 Sep 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Male or female ages 40-80 years, inclusive
- Clinical diagnosis of Parkinson's disease, stage 1, 2 or 3 as determined by the Hoehn and Yahr Scale
- Meet criteria for major depressive disorder (MDD) as determined by the Mini-International Neuropsychiatric Interview (MINI), and at least 15 on the MADRS, which has shown maximum discrimination between depressed and non-depressed PD patients.
- For women of reproductive potential, use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation, as well as a negative pregnancy test at screening.
- Abstinence from drugs of abuse, other than alcohol, cannabis, nicotine and caffeine for the duration of the study.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Provision of signed and dated informed consent form.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Presence of Dementia and a Montreal Cognitive Assessment (MoCA) score of less than 18.
- A primary psychiatric disorder (as determined by the MINI) except for MDD
- Active suicidal ideation with intent
- History of substance dependence in the last 2 years
- Current substance use disorder, except tobacco use disorder
Show all 16Show fewer
- Prior clinical psychiatric treatment with ketamine or prior recreational use of ketamine
- A history of or current significant medical (e.g. cardiovascular, renal), or neurological (e.g. cerebrovascular, seizure, traumatic brain injury) illness other than PD that is unstable and significantly increase their risk and/or might affect the study objectives, as determined by study physicians
- Uncontrolled hypertension, defined as average blood pressure greater than or equal to 140 mmHg or an average diastolic blood pressure greater than or equal to 90 mmHg among those patients who have hypertension.
- Orthostatic hypotension (OH) that presents with symptoms sustained longer than a few minutes (e.g., light-headedness, blurred vision, dizziness, weakness, fatigue) or with syncope. OH is defined by a decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within 3 minutes of standing compared with blood pressure from the sitting position.
- Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines.
- Any condition or finding that in the judgement of the PI significantly increases risk or significantly reduces the likelihood of benefit from participation in the study.
- For participation in the PET/fMRI only:
- Prior radiation exposure for research purposes within such that participation in this study would place them over FDA limits for annual radiation exposure (5 rem per yr)
- Contraindications to MRI scanning.
- Presence of a bleeding disorder as determined by the PT/INR (Prothrombin time and international normalized ratio) test
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06510
About this study
Official title: Ketamine for the Treatment of Depression in Parkinson's Disease (KET-PD)
The main purpose of this study is to examine the efficacy and safety of a repeated dosing ketamine infusion paradigm compared to placebo in individuals with PD.
A subset of participants in each arm will undergo baseline and post-treatment PET and fMRI scans, to examine whether changes in synaptic density and reorganization of functional networks underlie ketamine's putative antidepressant effects in PD.
Read the detailed description
This study will assess the efficacy of ketamine for the treatment of depression in Parkinson's disease (PD), in a parallel, double-blind, placebo controlled randomized clinical trial (RCT). Imaging will be used to examine the mechanistic effects of ketamine treatment. Specifically, the investigators will use positron emission tomography (PET) to measure synaptic density and functional magnetic resonance imaging (fMRI) to measure functional connectivity. The investigators hypothesize that a course of ketamine treatment will result in a significant reduction in depression severity compared to placebo. Mechanistically, ketamine will result in a reorganization of functional networks and an increase in synaptic density.
- Conditions
- Parkinson's Disease, Depression
- Being tested
- Ketamine Infusion, Placebo - Saline Infusion
- Keywords
- Ketamine Treatment
- 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.
Ketamine InfusionDrug
Participants will receive 6 infusions of ketamine (0.5 mg/kg IV, up to 60 mg total) , administered over 40 minutes while on continuous cardiac monitoring and oximetry
Placebo - Saline InfusionOther
Participants will receive 6 infusions of saline administered over 40 minutes while on continuous cardiac monitoring and oximetry
| Study group | Role | What they receive |
|---|---|---|
| Ketamine Infusion | Experimental | Participants will receive 6 infusions of ketamine (0.5 mg/kg IV, up to 60 mg total) , administered over 40 minutes while on continuous cardiac monitoring and oximetry Receives: Drug: Ketamine Infusion |
| Saline Infusion | Placebo comparator | Participants will receive 6 infusions of placebo (saline IV), administered over 40 minutes while on continuous cardiac monitoring and oximetry Receives: Other: Placebo - Saline Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Depression Severity
The primary outcome of depression severity post-treatment will be compared between groups using a linear mixed model with group (ketamine, placebo) included as a between-subjects factor and time (baseline, weeks 1, 2, 3) included as a within-subjects factor. The scale used to measure depression severity is called The Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. The overall score ranges from 0 to 60, higher MADRS score indicates more severe depression.
Measured: Baseline, Week 1, Week 2, and Week 3
Secondary outcomes (13)
Change in Blood pressure: systolic
Changes in systolic and diastolic blood pressure determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in Blood pressure: diastolic
Changes in systolic and diastolic blood pressure determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in Heart rate
Changes in heart rate determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in Respiration
Changes in respiration determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in O2 saturation
Changes in O2 saturation determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in ECG
Changes in ECG indicating a cardiac event such as an arrhythmia or ischemia determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in CBC with differential
Changes in CBD with differential determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in complete metabolic panel
Changes in complete metabolic panel determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in TFTs
Changes in TFTs determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Change in routine urinalysis
Changes in routine urinalysis determined as clinically significant by the Investigator
Measured: Baseline and up to 19 days after last administration of study intervention
Adverse events
Assessed by CTCAE v5.0 and the abbreviated version of the SAFTEE-GI and -SI to assess all body systems
Measured: Baseline and up to 32 days after last administration of study intervention
Change in synaptic density
The change in synaptic (SV2A) density (measured using [11C]UCB-J PET) between baseline and post-intervention scans will be measured across regions of interest
Measured: Baseline, Week 3
Change in network function
The change in network function will be measured by comparing fMRI functional connectivity between baseline and post-intervention scans
Measured: Baseline, Week 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2021
- Study start23 Nov 2021
- Primary completion24 Sep 2025
- Study completion24 Sep 2025
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 Yale UniversityThe 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Principal investigator, Sophie Holmes, Yale University
- Investigators
- Sophie E. Holmes, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04944017
- Sponsor's protocol ID
- 2000030394
- Other IDs
- DO NOT RELEASE
- Acronym
- KET-PD
- Status last verified
- Nov 2025
- First submitted
- 22 Jun 2021
- Last updated
- 8 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine for the Treatment of Depression in Parkinson's Disease (KET-PD)
- ClinicalTrials.gov ID
- NCT04944017
- Acronym / sponsor ID
- KET-PD / 2000030394
- Conditions
- Parkinson's Disease, Depression
- Keywords
- Ketamine Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Study start
- 23 Nov 2021 (actual)
- Primary completion
- 24 Sep 2025 (actual)
- Study completion
- 24 Sep 2025 (actual)
- First posted
- 29 Jun 2021 (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.
The main purpose of this study is to examine the efficacy and safety of a repeated dosing ketamine infusion paradigm compared to placebo in individuals with PD.
A subset of participants in each arm will undergo baseline and post-treatment PET and fMRI scans, to examine whether changes in synaptic density and reorganization of functional networks underlie ketamine's putative antidepressant effects in PD.
Detailed description
This study will assess the efficacy of ketamine for the treatment of depression in Parkinson's disease (PD), in a parallel, double-blind, placebo controlled randomized clinical trial (RCT). Imaging will be used to examine the mechanistic effects of ketamine treatment. Specifically, the investigators will use positron emission tomography (PET) to measure synaptic density and functional magnetic resonance imaging (fMRI) to measure functional connectivity. The investigators hypothesize that a course of ketamine treatment will result in a significant reduction in depression severity compared to placebo. Mechanistically, ketamine will result in a reorganization of functional networks and an increase in synaptic density.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine Infusion | Experimental | Drug: Ketamine InfusionParticipants will receive 6 infusions of ketamine (0.5 mg/kg IV, up to 60 mg total) , administered over 40 minutes while on continuous cardiac monitoring and oximetry |
| Saline Infusion | Placebo comparator | Other: Placebo - Saline InfusionParticipants will receive 6 infusions of placebo (saline IV), administered over 40 minutes while on continuous cardiac monitoring and oximetry |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female ages 40-80 years, inclusive
- Clinical diagnosis of Parkinson's disease, stage 1, 2 or 3 as determined by the Hoehn and Yahr Scale
- Meet criteria for major depressive disorder (MDD) as determined by the Mini-International Neuropsychiatric Interview (MINI), and at least 15 on the MADRS, which has shown maximum discrimination between depressed and non-depressed PD patients.
- For women of reproductive potential, use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation, as well as a negative pregnancy test at screening.
- Abstinence from drugs of abuse, other than alcohol, cannabis, nicotine and caffeine for the duration of the study.
Key exclusion criteria (16 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Presence of Dementia and a Montreal Cognitive Assessment (MoCA) score of less than 18.
- A primary psychiatric disorder (as determined by the MINI) except for MDD
- Active suicidal ideation with intent
- History of substance dependence in the last 2 years
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 |
|---|---|---|
| Ketamine InfusionParticipants will receive 6 infusions of ketamine (0.5 mg/kg IV, up to 60 mg total) , administered over 40 minutes while on continuous cardiac monitoring and oximetry | Drug | Ketamine Infusion |
| Placebo - Saline InfusionParticipants will receive 6 infusions of saline administered over 40 minutes while on continuous cardiac monitoring and oximetry | Other | Saline Infusion |
Primary outcome
Change in Depression Severity
Time frame: Baseline, Week 1, Week 2, and Week 3
The primary outcome of depression severity post-treatment will be compared between groups using a linear mixed model with group (ketamine, placebo) included as a between-subjects factor and time (baseline, weeks 1, 2, 3) included as a within-subjects factor. The scale used to measure depression severity is called The Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. The overall score ranges from 0 to 60, higher MADRS score indicates more severe depression.
13 secondary outcomes
Change in Blood pressure: systolic
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in Blood pressure: diastolic
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in Heart rate
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in Respiration
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in O2 saturation
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in ECG
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in CBC with differential
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in complete metabolic panel
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in TFTs
Time frame: Baseline and up to 19 days after last administration of study intervention
Change in routine urinalysis
Time frame: Baseline and up to 19 days after last administration of study intervention
Adverse events
Time frame: Baseline and up to 32 days after last administration of study intervention
Change in synaptic density
Time frame: Baseline, Week 3
Change in network function
Time frame: Baseline, Week 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2025.
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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. This study is not recruiting at the moment.
Sophie E. Holmes, PhD principal investigator
Yale University
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 Infusion in people with Parkinson's Disease and Depression, run by Yale University 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 7 inclusion and 16 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: finished, as of the sponsor's last update on 8 Dec 2025. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Depression Severity (time frame: Baseline, Week 1, Week 2, and Week 3). 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 8 Dec 2025.