Imaging Depression in Parkinson's Disease

Identifying the Neural Basis of Depression in Parkinson's Disease

The goal of this observational study is to identify targetable neural substrates of depression in Parkinson's Disease for the first time in people with Parkinson's between the ages of 40 and 80, who are experiencing symptoms of depression.

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease; Major Depressive Disorder
• Intervention / Treatment: Radiation: 11C-UCB-J; Drug: ketamine hydrochloride

Detailed Description

This study will compare people with Parkinson's Disease and depression to individuals with Parkinson's Disease without Major Depressive Disorder, Major Depressive Disorder with no Parkinson's, and Healthy Controls. Up to 30 participants will be recruited and enrolled for each of these 4 groups. Participants will be asked to complete one PET and one MRI scan along with study assessments. Once screening and consent is completed, participants will be scheduled for PET and MRI scans. The total duration for participants in this study is 7 hours, including the screening visit and then one additional visit for the scans.

There will also be a small subset (opt-in) who will receive a single dose of ketamine to determine the ability of ketamine to target these mechanisms and initiate an associated antidepressant response. If the participant is opting into the ketamine arm, the investigators will ask them to come in for one single-dose of ketamine and complete another PET and MRI scan post-ketamine treatment.

The main questions it aims to answer are: 1) Will the Parkinson's depression group exhibit a distinct pattern of synaptic deficits compared to other groups? 2) Will there be differences in functional connectivity across groups? 3) Are there associations between synaptic density and functional connectivity across groups? 4) Will ketamine increase synaptic density in PD-affected and mood-related circuitry, and will that be associated with an antidepressant response?

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sophie Holmes; Phone Number: 2036854066; Email: sophie.holmes@yale.edu
• Study Contact Backup: Name: Libby DiDomizio; Phone Number: 2039476313; Email: libby.didomizio@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
      • Contact: Sophie Holmes, PhD; Phone Number: 203-685-4066; Email: sophie.holmes@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Study Population

Community and health services

Description

Inclusion Criteria:

1. Age 40-80.
2. For women of reproductive potential, a negative pregnancy test at screening and scanning
3. For PD patients, clinical diagnosis of PD, able to consent and tolerate PET procedures
4. For PD depression patients - at least moderate symptom severity as determined by at least 15 on the MADRS, which has shown maximum discrimination between depressed and non-depressed PD patients.
5. For dPD patients undergoing ketamine, abstinence from drugs of abuse, other than alcohol, cannabis, nicotine and caffeine for the duration of the study. Patients with substance use disorders as defined by the DSM-5 will be excluded.

Exclusion Criteria:

1. Dementia (Montreal Cognitive Assessment (MoCA) score <21)
2. A significant primary DSM-5 psychiatric disorder except for MDD
3. 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.
4. Prior radiation exposure for research purposes within such that participation in this study would place them over FDA limits for annual radiation exposure
5. Medications affecting SV2A availability (e.g. levetiracetam)
6. For dPD patients receiving ketamine, 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.
7. Contraindications to MRI.
8. For patients undergoing arterial sampling for the PET scan: Iodine allergy, bleeding disorder and/or use of blood thinning medication
9. Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Parkinson's Disease with Major Depressive Disorder; This study aims to identify mechanisms unique to patients with both Parkinson's Disease and Major Depressive Disorder.

Radiation: 11C-UCB-J; Radiotracer for imaging; Drug: ketamine hydrochloride; There will be a small subset (opt-in) who will receive a single dose of ketamine to determine the ability of ketamine to target these mechanisms and initiate an associated antidepressant response. If the participant is opting into the ketamine arm, the investigators will ask them to come in for one single-dose of ketamine and complete another PET and MRI scan post-ketamine treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Åsberg Depression Rating Scale (MADRS)	This assessment stratifies severity of depressive episodes in adults. Ratings are based on clinical interview with the patient. Use clinical judgment to determine whether the rating lies on the defined scale steps (0, 2, 4, 6 points) or between them (1, 3, 5 points, denoted as "(Worsening symptoms)").The MADRS scoring instructions indicate that a total score ranging from 0 to 6 indicates that the patient is in the normal range (no depression), a score ranging from 7 to 19 indicates "mild depression," 20 to 34 indicates "moderate depression," a score of 35 and greater indicates "severe depression," and a total score of 60 or greater indicates "very severe depression."	One day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Binding potential (BPND)	Binding potential (BPND) reflects the ratio at equilibrium of specifically bound radioligand to that of non-displaceable radioligand in tissue. BPND maps will be generated using the simplified reference tissue method 2 (SRTM2) and the centrum semiovale (CS) as reference region.	One week

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: May 2, 2024
• First Submitted That Met QC Criteria: May 2, 2024
• First Posted (Actual): May 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Imaging
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurodegenerative Diseases; Mood Disorders; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Depressive Disorder; Depressive Disorder, Major; Parkinson Disease; Organic Chemicals; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Ketamine; 1-((3-(methylpyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one
• Other Study ID Numbers: 2000037090; R01NS125482-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No