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Ketamine for the Treatment of Depression in Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT04944017
Recruitment Status : Not yet recruiting
First Posted : June 29, 2021
Last Update Posted : June 29, 2021
Sponsor:
Collaborator:
Fox (Michael J.) Foundation for Parkinson's Research
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE June 22, 2021
First Posted Date  ICMJE June 29, 2021
Last Update Posted Date June 29, 2021
Estimated Study Start Date  ICMJE August 2021
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2021)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2021)
  • Change in synaptic density [ Time Frame: Baseline, Week 3 ]
    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 [ Time Frame: Baseline, Week 3 ]
    The change in network function will be measured by comparing fMRI functional connectivity between baseline and post-intervention scans.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine for the Treatment of Depression in Parkinson's Disease
Official Title  ICMJE Ketamine for the Treatment of Depression in Parkinson's Disease
Brief Summary

The main purpose of this study is to examine the efficacy, safety and mechanistic underpinnings 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Parkinson's Disease
  • Depression
Intervention  ICMJE
  • Drug: Ketamine Infusion
    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
  • Other: Placebo - Saline Infusion
    Participants will receive 6 infusions of saline administered over 40 minutes while on continuous cardiac monitoring and oximetry
Study Arms  ICMJE
  • Experimental: Ketamine Infusion
    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: Drug: Ketamine Infusion
  • Placebo Comparator: Saline Infusion
    Participants will receive 6 infusions of placebo (saline IV), administered over 40 minutes while on continuous cardiac monitoring and oximetry
    Intervention: Other: Placebo - Saline Infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 22, 2021)
56
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2024
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female ages 40-70 years, inclusive
  2. Clinical diagnosis of Parkinson's disease, stage 1 or 2 as determined by the Hoehn and Yahr Scale
  3. Meet criteria for major depressive disorder (MDD) as determined by the Structured Clinical Interview for DSM-5 (SCID-575), and at least 15 on the MADRS, which has shown maximum discrimination between depressed and non-depressed PD patients.
  4. Physically healthy by medical history, physical, ECG and laboratory examinations.
  5. 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.
  6. Abstinence from drugs of abuse, other than alcohol, cannabis, nicotine and caffeine for the duration of the study.
  7. Stated willingness to comply with all study procedures and availability for the duration of the study.
  8. 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 (Montreal Cognitive Assessment (MoCA) score < 21)
  2. A significant DSM-5 psychiatric disorder except for MDD
  3. Active suicidal ideation with intent
  4. History of substance dependence
  5. Current DSM-5 substance use disorder, except tobacco use disorder
  6. Prior participation in a ketamine study, prior clinical psychiatric treatment with ketamine, or prior recreational use of ketamine
  7. A history of significant medical (e.g. cardiovascular, renal), or neurological (e.g. cerebrovascular, seizure, traumatic brain injury) illness other than PD that is unstable and/or might affect the study objectives
  8. History of 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 in English.

    For participation in the PET/fMRI only:

  11. 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)
  12. Contraindications to MRI scanning.
  13. Presence of a bleeding disorder as determined by the PT/INR (Prothrombin time and international normalized ratio) test
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sophie E. Holmes, PhD sophie.holmes@yale.edu
Contact: Gerard Sanacora, MD 203 974 7560, Gerard.sanacora@yale.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04944017
Other Study ID Numbers  ICMJE 2000030394
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Fox (Michael J.) Foundation for Parkinson's Research
Investigators  ICMJE
Principal Investigator: Sophie E. Holmes, PhD Yale University
PRS Account Yale University
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP