Clinical trial NCT04944017: Ketamine for the Treatment of Depression in Parkinson's Disease
Official title: Ketamine for the Treatment of Depression in Parkinson's Disease (KET-PD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Parkinson's Disease
Depression
Keywords: Ketamine Treatment
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Fox (Michael J.) Foundation for Parkinson's Research
First posted: 2021-06-29
Enrollment: 56
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female ages 40-80 years, inclusive
2. Clinical diagnosis of Parkinson's disease, stage 1, 2 or 3 as determined by the Hoehn and Yahr Scale
3. 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.
4. 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.
5. Abstinence from drugs of abuse, other than alcohol, cannabis, nicotine and caffeine for the duration of the study.
6. Stated willingness to comply with all study procedures and availability for the duration of the study.
7. Provision of signed and dated informed consent form.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Presence of Dementia and a Montreal Cognitive Assessment (MoCA) score of less than 18.
2. A primary psychiatric disorder (as determined by the MINI) except for MDD
3. Active suicidal ideation with intent
4. History of substance dependence in the last 2 years
5. Current substance use disorder, except tobacco use disorder
6. Prior clinical psychiatric treatment with ketamine or prior recreational use of ketamine
7. 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
8. 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.
9. 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.
10. Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines.
11. 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:
12. 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)
13. Contraindications to MRI scanning.
14. Presence of a bleeding disorder as determined by the PT/INR (Prothrombin time and international normalized ratio) test

Primary outcomes:
measure: Change in Depression Severity
timeFrame: Baseline, Week 1, Week 2, and Week 3
Secondary outcomes:
measure: Change in Blood pressure: systolic
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in Blood pressure: diastolic
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in Heart rate
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in Respiration
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in O2 saturation
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in ECG
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in CBC with differential
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in complete metabolic panel
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in TFTs
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Change in routine urinalysis
timeFrame: Baseline and up to 19 days after last administration of study intervention
measure: Adverse events
timeFrame: Baseline and up to 32 days after last administration of study intervention
measure: Change in synaptic density
timeFrame: Baseline, Week 3
measure: Change in network function
timeFrame: Baseline, Week 3
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Sophie E. Holmes, PhD
role: PRINCIPAL_INVESTIGATOR
References: