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

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Institute of Mental Health (NIMH)
Study ID
NCT03065335
Phase
PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Accepted

Interventions

  • Ketamine — DRUG
    N-methyl-D-aspartate (NMDA) glutamate receptor (NMDA-R) antagonist
  • Placebo — OTHER
    Placebo comparator
  • Cobot TS MV robotic arm for TMS — DEVICE
    TMS-Cobot TS MV \[Axilum Robotics\] robotic arm for spatial positioning and orientation of the TMS coil
  • NeurOptics PLRTM-30000 Pupillometer — DEVICE
    The Neu-rOptics PLRTM-3000 Pupillometer will use quantitative infrared technology to objectively and accurately measure pupil size and dynamics.

Study Details

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 ...

Key Dates

Start date
May 25, 2017
Status verified
Oct 2025
Primary completion
Jan 1, 2027
Completion
Jan 1, 2028

Study Design

Enrollment
150 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Experimental: Metabolites Substudy
    Open-label, single dose of 0.5 mg/kg IV ketamine
  • Experimental: Phase I
    Medication taper, drug-free period, and baseline assessments
  • Experimental: Phase II, Arm 1
    Double-blind, single dose of 0.5 mg/kg IV ketamine
  • Experimental: Phase II, Arm 1b
    Double-blind, single dose of 0.5 mg/kg IV ketamine, concurrently with fMRI+EEG or MEG
  • Placebo Comparator: Phase II, Arm 2
    Double-blind, single dose of 0.5 mg/kg IV saline
  • Placebo Comparator: Phase II, Arm 2b
    Double-blind, single dose of 0.5 mg/kg IV saline, concurrently with fMRI+EEG or MEG.
  • Experimental: Phase III
    Double-blind, repeated dose of 0.5 mg/kg or 0.1 mg/kg IV ketamine
  • No Intervention: Phase IV
    Follow-up evaluations

Primary Outcome Measure

To demonstrate more robust neuropharmacodynamic effects measured by neuropharmacodynamic imaging (fMRI+EEG and MEG) of ketamine 0.5 mg/kg as compared to placebo administered over 40 minutes. [ Time Frame: Multiple ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
NIH Clinical Center Office of Patient Recruitment (OPR)
[email protected]
800-411-1222

Find similar trials in Bethesda, MD

By condition
Depression
By specialty
PsychiatryMental healthBehavioral health
By research site
National Institutes of Health Clinical Center· Bethesda, MD

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