Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder

Summary

Background:

Most medications that treat depression take weeks or months to work. Researchers want to develop fast-acting treatments. One dose of ketamine has a rapid antidepressant effect. For most people, this lasts a week or less. Repeated doses of ketamine may help maintain this effect.

Objective:

Main Study: To study the effects of ketamine in treating depression.

Ketamine Metabolites Substudy: To study how ketamine effects brain chemistry.

To study how ketamine effects the brain. This is done by looking at metabolites, which are created when a drug is broken down.

Eligibility:

Main Study: People ages 18-65 with major depressive disorder and healthy volunteers

Ketamine Metabolites Substudy: Healthy volunteers ages 18-65

Design:

Main Study:

Participants will be screened in another study, with:

* Medical and psychiatric history
* Psychiatric and physical exam
* Blood, urine, and heart tests

Participants will be inpatients at NIH for 4 phases totaling 14-20 weeks.

Phase I (2-7 weeks):

* Gradually stop current medications
* MRI: Participants lie and perform tasks in a machine that takes pictures of the body.
* Mood and thinking tests
* Blood and urine tests
* Sleep test: Monitors on the skin record brain waves, breathing, heart rate, and movement during sleep.
* Transcranial magnetic stimulation: A coil on the scalp gives an electrical current that affects brain activity.
* Stress tests: Electrodes on the skin measure reactions to loud noises or electric shocks.

Phase I tests are repeated in Phases II and III and in the final visit.

Phase II (4-5 weeks):

* 4 weekly IV infusions of ketamine or a placebo during an MRI or MEG. For the MEG, a cone over the head records brain activity.

Phase III (optional):

* 8 infusions of ketamine over 4 weeks

Phase IV (optional):

* Symptoms monitoring for 4 weeks
* Participants will have a final visit. They will be offered standard treatment at NIH for up to 2 months.

Ketamine Metabolites Substudy:

Participants will be screened in another study, with:

* Medical and psychiatric history
* Psychiatric and physical exam
* Blood, urine, and heart tests

Participants will be inpatients at NIH for 4 days.

Study Procedures:

Mood and thinking tests

Blood and urine tests

1 infusion of ketamine

Spinal tap and spinal catheter: Used to get samples of cerebrospinal fluid (CSF). This is a fluid that moves around and within the brain and spinal cord. Studying CSF will help us learn how ketamine effects brain chemistry

Conditions

• Healthy Volunteer
• Major Depressive Disorder
• Depression

Interventions

DRUG

Ketamine

N-methyl-D-aspartate (NMDA) glutamate receptor (NMDA-R) antagonist

OTHER

Placebo

Placebo comparator

DEVICE

Cobot TS MV robotic arm for TMS

TMS-Cobot TS MV \[Axilum Robotics\] robotic arm for spatial positioning and orientation of the TMS coil

DEVICE

NeurOptics PLRTM-30000 Pupillometer

The Neu-rOptics PLRTM-3000 Pupillometer will use quantitative infrared technology to objectively and accurately measure pupil size and dynamics.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  lead NIH

Principal Investigators

• Carlos A Zarate, M.D. · National Institute of Mental Health (NIMH)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-05-25

Primary Completion

2027-01-01

Completion

2028-01-01

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations