RecruitingPhase 1

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

United States150 participantsStarted 2017-05-25

Plain-language 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

Who can participate

Age range

18 Years – 65 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

. 18 to 65 years of age.
. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
. All subjects must have undergone a screening assessment under either protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers" or protocol 17-M-0181 ("Recruitment and Characterization of Research Volunteers for NIMH Intramural Studies").
. Agree to be hospitalized
. At the initial study enrollment, subjects must have fulfilled DSM-IV or DSM-5 criteria for Major Depression, single episode or recurrent. Subjects must be experiencing a current major depressive episode of at least 2 weeks duration.
. At the initial screening and beginning of Phases II and III, subjects must have a baseline score on the MADRS \>= 20 and YMRS of \< 12.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Since this is a Phase 1 trial focused on understanding how ketamine affects the brain through imaging and brain wave measurements rather than testing it as a treatment, would participating actually give me access to ketamine as a therapy, or is the main purpose scientific data collection?
2This trial involves repeated ketamine infusions alongside brain scans using fMRI, EEG, and MEG — given my current depression severity, is my condition stable enough that the demands of this kind of intensive research schedule would be manageable for me?
3One part of this study is specifically looking at whether ketamine's breakdown products cross into the brain — does that mean there are still open questions about the drug's safety profile that my doctor thinks I should understand before considering any ketamine-related study or treatment?
4Since the trial compares ketamine to a placebo, is there a chance I could be assigned to the placebo group and receive no active treatment during the study, and how might that affect my depression in the short term?
5Given that standard antidepressant treatments exist and some ketamine infusion clinics already offer off-label treatment, would my doctor recommend trying an established therapy first rather than enrolling in a research study where the goal is brain imaging rather than my personal treatment outcome?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

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.

Timeframe: Multiple

Ketamine Metabolites Substudy: To determine if ketamine metabolites cross the blood brain barrier and enter the brain during ketamine IV administration.

Timeframe: Multiple

Trial details

NCT IDNCT03065335

SponsorNational Institute of Mental Health (NIMH)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2027-01-01

Contact for this trial

Adilah M Kirton

(301) 549-0315 adilah.meredith-kirton@nih.gov

View on ClinicalTrials.gov More Healthy Volunteer trials

Plain-language summary

Who can participate

Age range

18 Years – 65 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

. 18 to 65 years of age.
. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
. All subjects must have undergone a screening assessment under either protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers" or protocol 17-M-0181 ("Recruitment and Characterization of Research Volunteers for NIMH Intramural Studies").
. Agree to be hospitalized
. At the initial study enrollment, subjects must have fulfilled DSM-IV or DSM-5 criteria for Major Depression, single episode or recurrent. Subjects must be experiencing a current major depressive episode of at least 2 weeks duration.
. At the initial screening and beginning of Phases II and III, subjects must have a baseline score on the MADRS \>= 20 and YMRS of \< 12.

What they're measuring

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.

Timeframe: Multiple

Ketamine Metabolites Substudy: To determine if ketamine metabolites cross the blood brain barrier and enter the brain during ketamine IV administration.

Timeframe: Multiple

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

Plain-language summary

Who can participate

Inclusion criteria

Questions worth asking your doctor

Questions for the trial coordinator

What they're measuring

Trial details

Contact for this trial

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

Plain-language summary

Who can participate

Inclusion criteria

Questions worth asking your doctor

Questions for the trial coordinator

What they're measuring

Trial details

Contact for this trial

Exclusion criteria