Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression

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.

...

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)

Arm 1 and 2 Experimental Intervention

DRUG

Placebo

Arm 1 and 2 Control Intervention

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  lead NIH

Principal Investigators

• Carlos A Zarate, M.D. · National Institute of Mental Health (NIMH)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-11-06

Primary Completion

2027-07-01

Completion

2027-07-01

FDA Drug

Yes

Countries

• United States

Study Locations