Ketamine for the Treatment of Depression in Parkinson's Disease

NCT04944017 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 2000030394DO NOT RELEASE
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease; Depression

Keywords

Ketamine Treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Week 1, Week 2, and Week 3

Secondary Outcomes (13)

• Change in Blood pressure: systolic

  Baseline and up to 19 days after last administration of study intervention

• Change in Blood pressure: diastolic

  Baseline and up to 19 days after last administration of study intervention

• Change in Heart rate

  Baseline and up to 19 days after last administration of study intervention

• Change in Respiration

  Baseline and up to 19 days after last administration of study intervention

• Change in O2 saturation

  Baseline and up to 19 days after last administration of study intervention

Study Arms (2)

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

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

Other: Placebo - Saline Infusion

Interventions

Ketamine Infusion DRUG

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

Ketamine Infusion

Placebo - Saline Infusion OTHER

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

Saline Infusion

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Yale University: lead
• Fox (Michael J.) Foundation for Parkinson's Research: collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Depression

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Behavioral Symptoms; Behavior

Study Officials

• Sophie E. Holmes, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Study Record Dates

• First Submitted: June 22, 2021
• First Posted: June 29, 2021
• Study Start: November 23, 2021
• Primary Completion: September 24, 2025
• Study Completion: September 24, 2025
• Last Updated: December 8, 2025

Record last verified: 2025-11

Locations

US (1)