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Ketamine for the Treatment of Depression in Parkinson's Disease (KET-PD)

Primary Purpose

Parkinson's Disease, Depression

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ketamine Infusion

Placebo - Saline Infusion

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Ketamine Treatment

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female ages 40-75 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.

Exclusion Criteria:

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

Presence of Dementia (Montreal Cognitive Assessment (MoCA) score < 21)
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
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

Sites / Locations

Yale New Haven HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketamine Infusion

Saline Infusion

Arm Description

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

Participants will receive 6 infusions of placebo (saline IV), administered over 40 minutes while on continuous cardiac monitoring and oximetry

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in Blood pressure: systolic

Changes in systolic and diastolic blood pressure determined as clinically significant by the Investigator

Change in Blood pressure: diastolic

Changes in systolic and diastolic blood pressure determined as clinically significant by the Investigator

Change in Heart rate

Changes in heart rate determined as clinically significant by the Investigator

Change in Respiration

Changes in respiration determined as clinically significant by the Investigator

Change in O2 saturation

Changes in O2 saturation determined as clinically significant by the Investigator

Change in ECG

Changes in ECG indicating a cardiac event such as an arrhythmia or ischemia determined as clinically significant by the Investigator

Change in CBC with differential

Changes in CBD with differential determined as clinically significant by the Investigator

Change in complete metabolic panel

Changes in complete metabolic panel determined as clinically significant by the Investigator

Change in TFTs

Changes in TFTs determined as clinically significant by the Investigator

Change in routine urinalysis

Changes in routine urinalysis determined as clinically significant by the Investigator

Adverse events

Assessed by CTCAE v5.0 and the abbreviated version of the SAFTEE-GI and -SI to assess all body systems

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

Change in network function

The change in network function will be measured by comparing fMRI functional connectivity between baseline and post-intervention scans

Full Information

NCT ID

NCT04944017

First Posted

June 22, 2021

Last Updated

March 8, 2023

Sponsor

Yale University

Collaborators

Fox (Michael J.) Foundation for Parkinson's Research

1. Study Identification

Unique Protocol Identification Number

NCT04944017

Brief Title

Ketamine for the Treatment of Depression in Parkinson's Disease

Acronym

KET-PD

Official Title

Ketamine for the Treatment of Depression in Parkinson's Disease (KET-PD)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 23, 2021 (Actual)

Primary Completion Date

August 2024 (Anticipated)

Study Completion Date

August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Yale University

Collaborators

Fox (Michael J.) Foundation for Parkinson's Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson's Disease, Depression

Keywords

Ketamine Treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ketamine Infusion

Arm Type

Experimental

Arm Description

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

Arm Title

Saline Infusion

Arm Type

Placebo Comparator

Arm Description

Participants will receive 6 infusions of placebo (saline IV), administered over 40 minutes while on continuous cardiac monitoring and oximetry

Intervention Type

Drug

Intervention Name(s)

Ketamine Infusion

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo - Saline Infusion

Intervention Description

Participants will receive 6 infusions of saline administered over 40 minutes while on continuous cardiac monitoring and oximetry

Primary Outcome Measure Information:

Title

Change in Depression Severity

Description

Time Frame

Baseline, Week 1, Week 2, and Week 3

Secondary Outcome Measure Information:

Title

Change in Blood pressure: systolic

Description

Changes in systolic and diastolic blood pressure determined as clinically significant by the Investigator

Time Frame