Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression
Eligible age
18–70 yrs
Accepts
All genders
Locations
1 state
Healthy volunteers
No
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About this study
Background: Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD. Objective: To test a study drug (HNK) in people with MDD. Eligibility: People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254. Design: Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity. HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule: They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study. They will receive no drugs for 2 to 3 weeks. They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study. One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo. ...
Sponsor: National Institute of Mental Health (NIMH)
You may not qualify if…
- ✕ An individual who meets any of the following criteria will be excluded from participation in this study:
- ✕ 1. Current use of disallowed concomitant medications or transcranial magnetic stimulation (TMS) two weeks prior to the start of Phase II.
- ✕ 2. Treatment with a reversible monoamine oxidase inhibitor (MAOI) four weeks prior to the start of Phase II.
- ✕ 3. Treatment with fluoxetine, aripiprazole, or brexpiprazole five weeks prior to the start of Phase II.
- ✕ 4. Treatment with clozapine or electroconvulsive therapy (ECT) four weeks prior to the start of Phase II.
- ✕ 5. Ongoing treatment with moderate or strong CYP3A4/5 inhibitors or inducers
- ✕ 6. Lifetime history of deep brain stimulation.
- ✕ 7. Previous antidepressant non-response to ketamine or esketamine (full course).
Where it's recruiting
Bethesda
Source: ClinicalTrials.gov · NCT06511908 · last updated 2026-07-10