Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in P… (NCT03973268) | Clinical Trial Compass
RecruitingPhase 1
Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression
United States70 participantsStarted 2020-01-21
Plain-language summary
Background:
Most drugs that treat mood disorders take a long time to work. Ketamine works within hours. A dose can last for a week or more. Certain receptors in the brain might help ketamine work. A drug that blocks these receptors might affect how it works.
Objective:
To see if the antidepressant response of ketamine is linked to AMPA receptors.
Eligibility:
Adults ages 18-70 with major depression disorder without psychotic features
Design:
Participants will be screened under protocol 01-M-0254. They will have blood tests and a physical exam.
Participants will stay at the NIH Clinical Center for 5 weeks.
Phase 1 lasts 4 weeks. For 2 weeks, participants will taper off their psychiatric medicine. Then they will have the following tests:
* Blood draws
* Psychological tests
* MRI: Participants will lie in a machine that takes pictures of their brain.
* MEG: Participants will lie down and do tasks. A cone lowered on their head will record brain activity.
* Optional sleep tests: Electrodes on the scalp and body and belts around the body will monitor participants while they sleep.
* Optional TMS: Participants will do tasks while a wire coil is held on their scalp. An electrical current will pass through the coil that affects brain activity.
For phase 2, on day 0 participants will take the study drug or a placebo orally. While having a MEG, they will get ketamine infused into a vein in one arm while blood is drawn from a vein in the other arm. On day 1, participants will again take the study drug or a placebo orally. On days 3-7, they will repeat many of the phase 1 tests. Days 8 and 9 are optional and include an open label ketamine treatment and many of the phase 1 tests.
Who can participate
Age range
18 Years – 70 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 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 subjects must have undergone a screening assessment under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers".
. Subjects 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).
. Subjects must have an initial score on the MADRS greater than or equal to 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); a failed adequate trial of ECT \[or TMS\] would count as an adequate antidepressant trial.
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.
1This trial is testing a specific theory about how ketamine works by combining it with a drug called perampanel — can you explain what that means for me, and whether being part of a mechanism-focused Phase 1 study means the main goal is understanding how the drug works rather than guaranteeing I'll feel better?
2Since this is a Phase 1 trial, what is actually known so far about the safety of combining ketamine infusions with perampanel, and are there risks I should be aware of that might be different from ketamine alone?
3The study uses a placebo-controlled design where some participants get ketamine plus perampanel and others get ketamine plus a placebo — can you walk me through what that means for my chances of receiving the full experimental treatment, and how that might affect my depression during the trial period?
4Given that my depression has already been treatment-resistant, would enrolling in this research study be a reasonable next step, or are there other standard treatments I haven't yet tried that might be worth considering first?
5The trial measures depression improvement using a rating scale called the MADRS — how does this measurement compare to how you and I would actually track whether my symptoms are getting better in real life, and what happens to my care if I don't show improvement during the study?
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
1
Acute Antidepressant Efficacy: Change from baseline Montgomery Asberg Depression Rating Scale (MADRS) score post ketamine infusion
Timeframe: Baseline, Day 1
2
Continued Antidepressant Efficacy: Change from baseline MADRS score post treatment with ketamine with perampanel versus placebo.
. Current major depressive episode lasting at least four weeks
. Agree to be hospitalized
Exclusion criteria
. Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-5.
. Subjects 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. In addition, subjects who currently are using drugs (except for caffeine or nicotine) must not have used illicit substances or known drugs of abuse in the 2 weeks prior to screening and must have a negative alcohol and drug urine test (except for prescribed benzodiazepines or stimulants) at screening.
. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease, coronary artery disease, atherosclerotic ischemic stroke, and atrial fibrillation), endocrinologic, neurologic, immunologic, or hematologic disease.
. 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 remain completely abstinent from sexual intercourse during the entire period of study participation (or until the last clinical labs and ratings). Participants able to become pregnant must have negative urine pregnancy tests no more than 24 hours prior to receiving the study drugs and undergoing imaging procedures.
. Subjects with one or more seizures without a clear and resolved etiology or current use of medication known to lower seizure threshold. History of seizure (regardless of age or etiology), history of epilepsy in self or first-degree relatives, stroke, brain surgery, head injury, or known structural brain lesion will be excluded from the TMS procedures.
. Presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.
. (For imaging procedures) Subjects with hearing loss that has been clinically evaluated and diagnosed and may be worsened through participation in imaging procedures