Depression study: Arm
Official title Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression
ClinicalTrials.gov ID: NCT03973268
What this study is testing
What is Arm 1, 2, 3 drug Interventions?
An investigational ketamine treatment being studied for major depression. Ketamine is designed to block NMDA receptors in the brain.
Also referred to as Ketamine.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The study aims to determine whether ketamine’s rapid mood‑boosting effect is linked to AMPA receptors in the brain.
- Who it's for
- Adults 18‑70 years old with major depressive disorder who do not have psychotic features.
- What's involved
- Participants will stay at the NIH Clinical Center for 5 weeks. They will undergo blood tests, physical exams, brain imaging (MRI, MEG), and optional sleep and TMS studies. On day 0 they receive either the study drug or placebo orally and ketamine via IV while MEG is recorded. On day 1 they take the drug or placebo again. Days 3‑7 repeat many of the earlier tests. Days 8‑9 are optional and include open‑label ketamine and further tests.
- Time commitment
- The study lasts 5 weeks, with daily visits for medication and tests, plus additional optional visits on days 8 and 9.
- Phase 1: an early, usually small safety study
- Time commitment: about 4 weeks
- You might receive a placebo (an inactive treatment) instead of the study drug, decided by chance. You may not know which one you got.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 70
You may be able to join if
- Phases I-II
- 18 to 70 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 people must have undergone a screening assessment under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and...
- people must fulfill DSM-IV or -5criteria for Major Depression (Major Depressive Disorder) without psychotic features, based on clinical assessment...
You likely can't join if
- Phases I-II
- Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-5.
- people with a history of substance abuse or dependence diagnosis (DSM-IV) or substance use disorder (DSM-5 equivalent) (except for caffeine or...
- Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease, coronary...
- Pregnant or nursing individuals or those who are physically able to become pregnant.
- people with one or more seizures without a clear and resolved etiology or current use of medication known to lower seizure threshold.
See the full eligibility criteria
- Phases I-II
- 18 to 70 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 people must have undergone a screening assessment under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers".
- people must fulfill DSM-IV or -5criteria for Major Depression (Major Depressive Disorder) without psychotic features, based on clinical assessment and informed by a structured diagnostic interview (SCID-P).
- people must have an initial score on the MADRS \>= 22 and a YMRS score of \<12 within one week of study entry and upon entry into Phase II.
- Lack of response to two adequate antidepressant trials, with [at least] one in the current major depressive episode, operationally defined using the Antidepressant Treatment History Form (ATHF)
- Current major depressive episode lasting at least four weeks
- Agree to be hospitalized Open-Label Ketamine Treatment
- Participants must have met all for and completed Study Phase II
- Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase III.
- Phases I-II
- Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-5.
- people with a history of substance abuse or dependence diagnosis (DSM-IV) or substance use disorder (DSM-5 equivalent) (except for caffeine or nicotine dependence) within the preceding 3 months.
- Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease, coronary artery disease, atherosclerotic ischemic stroke, and atrial fibrillation)...
- Pregnant or nursing individuals or those who are physically able to become pregnant. Participants who are physically able to become pregnant or cause a pregnancy must use at least one form of effective birth control or...
- people with one or more seizures without a clear and resolved etiology or current use of medication known to lower seizure threshold.
- Presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.
- Clinically significant abnormal laboratory tests.
- (For imaging procedures) people with hearing loss that has been clinically evaluated and diagnosed and may be worsened through participation in imaging procedures
- Positive HIV test
- Weight \> 119 kg
- Treatment with any concomitant psychiatric medication prior to entering Phase II. [Medications must be tapered during Phase I.]
- Treatment with any non-psychiatric medication/s.
- Any use of opioid medication in the past 3 months
- Treatment with a reversible monoamine oxidase inhibitor (MAOI) prior to entering Phase II. [Medications must be tapered during Phase I.]
- Treatment with fluoxetine or aripiprazole at the time of screening.
- Unwilling to stop undergoing structured, individualized psychotherapy. (Such therapy, including CBT, will not be permitted during Phases I and II of the study.)
- Presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clip).
- Participants who are uncomfortable in small closed spaces (have claustrophobia).
- Are unable to lie comfortably supine for up to 90 minutes and would feel uncomfortable in the MRI and MEG machines.
- people who, in the investigator s judgment, pose a current serious suicidal or homicidal risk.
- people who have a history of aggressive behavior towards others Open-Label Ketamine Treatment
- Intolerable or serious adverse reaction to ketamine during Phase II
- Participants with a positive urine for an illicit substance no more than 24 hours prior to ketamine treatment.
- Pregnant or nursing individuals or those who plan to become pregnant.
The study team makes the final eligibility decision.
Where it is enrolling
- Bethesda, Maryland, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The study runs about 4 weeks per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years to 70 years. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Bethesda, Maryland, United States. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.