Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression
NCT Number: NCT06511908
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Suicide|Depressive Disorder, Treatment-Resistant|Ketamine|Molecular Mechanisms of Pharmacological Action|Neurotransmitter Agents|Excitatory Amino Acid Agents|Physiological Effects of Drugs|Depressive Disorder, Major|Depressive Disorder|Depression|Mental Disorders|Mood Disorders|Behavioral Symptoms
Interventions: DRUG: (2R,6R)-hydroxynorketamine (0.25 to 2.0 mg/kg)|DRUG: Placebo
Sponsor: National Institute of Mental Health (NIMH)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 50
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-09-10
Completion Date: 2027-07-01
Locations: National Institutes of Health Clinical Center, Bethesda, Maryland, 20892, United States

Summary:
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.

...

Primary Outcome Measures: Change from baseline on Montgomery-Asberg Depression Rating Scale total scores, Clinical rating scale of depression, Baseline, Day 12
Secondary Outcome Measures: Change from baseline on Montgomery-Asberg Depression Rating Scale total scores, Clinical rating scale of depression, Baseline, 230 min post-drug, and Days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per Test Session.|Proportion of participants in remission (defined as Montgomery-Asberg Depression Rating Scale total score =10), Clinical rating scale of depression, Baseline, 230 min post-drug, and Days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per Test Session.|Proportion of participants achieving response (defined as a >/=50% reduction from baseline in Montgomery-Asberg Depression Rating Scale total score), Clinical rating scale of depression, Baseline, 230 min post-drug, and Days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per Test Session.|Change from baseline on item 10 (suicidality) of the Montgomery-Asberg Depression Rating Scale and total score on the Columbia Suicide Severity Rating Scale and the Scale for Suicide Ideation., Clinical rating scales of depression and suicidality, Baseline, 230 min post-drug, and Days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per Test Session.|Change from baseline on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Affect Schedule, Snaith-Hamilton Pleasure Scale, Temporal Experience of Pleasure Scale, and cognitive tasks., Clinical rating scales of mood, anxiety, and anhedonia, Baseline, 230 min post-drug, and Days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per Test Session.|Incidence of AEs and total scores using the Clinician Administered Dissociative States Scale, Young Mania Rating Scale, Brief Psychiatric Rating Scale, vital signs, changes in clinical laboratory evaluations, and electrocardiograms., Measures and evaluations assess various aspects of clinical condition, adverse events, and mood and anxiety symptomology, Baseline, 230 min post-drug, and Days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per Test Session.