Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06511908
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-19
Brief Title:
Investigation of the Antidepressant Effects of 2R6R-HNK an Enhancer of Synaptic Glutamate Release in Treatment-Resistant Depression
Sponsor:
None
Organization:
None
Study Overview
Official Title:
An Investigation of the Antidepressant Effects of 2R6R-HNK an Enhancer of Synaptic Glutamate Release in Treatment-Resistant Depression
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 2R6R-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
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 2R6R-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
Detailed Description:
Study Description
This is a randomized double-blind placebo-controlled crossover single-site study
This experimental study will assess the efficacy and safety of two weeks of 025 to 20 mgkg 2R6R-hydroxynorketamine HNK an enhancer of synaptic glutamate release The study may be conducted on an inpatient or outpatient basis
Objectives
Primary Objective
The primary objective is to evaluate the ability of 2R6R-HNK an enhancer of synaptic glutamate release to improve overall depressive symptomatology in participants with major depressive disorder MDD The efficacy of a two-week course of 2R6R-HNK will be compared to two weeks of saline placebo in a crossover study Montgomery-Asberg Depression Rating Scale MADRS score will serve as the main outcome measure
Secondary Objectives
1 To evaluate the antidepressant efficacy of 2R6R-HNK at days 0 230 min 1 2 3 4 7 8 10 11 and 12 compared to placebo in a crossover study as assessed by change from baseline on MADRS total scores
2 To determine whether 2R6R-HNK demonstrates superior antidepressant efficacy compared to placebo in a crossover study as assessed by the proportion of participants in remission defined as MADRS total score 10
3 To determine whether antidepressant response to 2R6R-HNK is superior to response to placebo in a crossover study as assessed by the proportion of participants achieving response defined as a 50 reduction from baseline in MADRS total score
4 To evaluate the antisuicidal ideation effects of 2R6R-HNK at days 0 230 min 1 2 3 4 7 8 10 11 and 12 compared to placebo in a crossover study as assessed by change from baseline on item 10 suicidality of the MADRS the Columbia Suicide Severity Rating Scale C-SSRS and the Scale for Suicide Ideation SSI
5 To investigate the effects of 2R6R-HNK on mood anxiety and anhedonia symptoms at days 0 230 min 1 2 3 4 7 8 10 11 and 12 compared to placebo in a crossover study as assessed by change from baseline on the Beck Depression Inventory Second Edition BDI-II Hamilton Depression Rating Scale HDRS Hamilton Anxiety Rating Scale HAM-A Positive and Negative Affect Schedule PANAS Snaith-Hamilton Pleasure Scale SHAPS and the Temporal Experience of Pleasure Scale TEPS as well as change from baseline on various cognitive tasks Auditory Somatosensory and Visual Evoked Fields Task Monetary Incentive Delay MID task Hariri Hamer task and Probabilistic Reward Task PRT
6 To assess the safety and tolerability of a two-week course of 2R6R-HNK compared to placebo in a crossover study by incidence of adverse events AEs and total scores on the Clinician Administered Dissociative States Scale CADSS Young Mania Rating Scale YMRS Brief Psychiatric Rating Scale BPRS vital signs changes in clinical laboratory evaluations and electrocardiograms ECGs
Endpoints
Endpoints Primary Endpoint
Effect of drug on the MADRS total score at day 12
Secondary Endpoints
Proportion of subjects in remission defined as MADRS total score 10 at days 0 230 min 1 2 3 4 7 8 10 11 and 12
Proportion of subjects with response defined as 50 reduction from baseline in MADRS total score at days 0 230 min 1 2 3 4 7 8 10 11 and 12
Effect of drug on MADRS total scores at days 0 230 min 1 2 3 4 7 8 10 11 and 12
Effect of drug on HDRS BDI-II BPRS CADSS C-SSRS HAM-A PANAS SHAPS SSI TEPS and YMRS total scores and the MADRS item 10 suicidality at days 0 230 min 1 2 3 4 7 8 10 11 and 12
Effect of drug on the Auditory Somatosensory and Visual Evoked Fields Task MID task Hariri Hamer task and PRT
Incidence and nature of adverse events vital signs weight and body mass index BMI changes physical examination changes clinical laboratory evaluations ECG
Surrogate Markers of Drug Effect Target Engagement and Antidepressant Response
Change in magnetoencephalography MEG spectral power gamma power
Change in brain glutamate levels using magnetic resonance spectroscopy MRS
Change in resting and task-based functional connectivity in functional magnetic resonance imaging fMRI
Change in peripheral biomarkers
This is a randomized double-blind placebo-controlled crossover single-site study
This experimental study will assess the efficacy and safety of two weeks of 025 to 20 mgkg 2R6R-hydroxynorketamine HNK an enhancer of synaptic glutamate release The study may be conducted on an inpatient or outpatient basis
Objectives
Primary Objective
The primary objective is to evaluate the ability of 2R6R-HNK an enhancer of synaptic glutamate release to improve overall depressive symptomatology in participants with major depressive disorder MDD The efficacy of a two-week course of 2R6R-HNK will be compared to two weeks of saline placebo in a crossover study Montgomery-Asberg Depression Rating Scale MADRS score will serve as the main outcome measure
Secondary Objectives
1 To evaluate the antidepressant efficacy of 2R6R-HNK at days 0 230 min 1 2 3 4 7 8 10 11 and 12 compared to placebo in a crossover study as assessed by change from baseline on MADRS total scores
2 To determine whether 2R6R-HNK demonstrates superior antidepressant efficacy compared to placebo in a crossover study as assessed by the proportion of participants in remission defined as MADRS total score 10
3 To determine whether antidepressant response to 2R6R-HNK is superior to response to placebo in a crossover study as assessed by the proportion of participants achieving response defined as a 50 reduction from baseline in MADRS total score
4 To evaluate the antisuicidal ideation effects of 2R6R-HNK at days 0 230 min 1 2 3 4 7 8 10 11 and 12 compared to placebo in a crossover study as assessed by change from baseline on item 10 suicidality of the MADRS the Columbia Suicide Severity Rating Scale C-SSRS and the Scale for Suicide Ideation SSI
5 To investigate the effects of 2R6R-HNK on mood anxiety and anhedonia symptoms at days 0 230 min 1 2 3 4 7 8 10 11 and 12 compared to placebo in a crossover study as assessed by change from baseline on the Beck Depression Inventory Second Edition BDI-II Hamilton Depression Rating Scale HDRS Hamilton Anxiety Rating Scale HAM-A Positive and Negative Affect Schedule PANAS Snaith-Hamilton Pleasure Scale SHAPS and the Temporal Experience of Pleasure Scale TEPS as well as change from baseline on various cognitive tasks Auditory Somatosensory and Visual Evoked Fields Task Monetary Incentive Delay MID task Hariri Hamer task and Probabilistic Reward Task PRT
6 To assess the safety and tolerability of a two-week course of 2R6R-HNK compared to placebo in a crossover study by incidence of adverse events AEs and total scores on the Clinician Administered Dissociative States Scale CADSS Young Mania Rating Scale YMRS Brief Psychiatric Rating Scale BPRS vital signs changes in clinical laboratory evaluations and electrocardiograms ECGs
Endpoints
Endpoints Primary Endpoint
Effect of drug on the MADRS total score at day 12
Secondary Endpoints
Proportion of subjects in remission defined as MADRS total score 10 at days 0 230 min 1 2 3 4 7 8 10 11 and 12
Proportion of subjects with response defined as 50 reduction from baseline in MADRS total score at days 0 230 min 1 2 3 4 7 8 10 11 and 12
Effect of drug on MADRS total scores at days 0 230 min 1 2 3 4 7 8 10 11 and 12
Effect of drug on HDRS BDI-II BPRS CADSS C-SSRS HAM-A PANAS SHAPS SSI TEPS and YMRS total scores and the MADRS item 10 suicidality at days 0 230 min 1 2 3 4 7 8 10 11 and 12
Effect of drug on the Auditory Somatosensory and Visual Evoked Fields Task MID task Hariri Hamer task and PRT
Incidence and nature of adverse events vital signs weight and body mass index BMI changes physical examination changes clinical laboratory evaluations ECG
Surrogate Markers of Drug Effect Target Engagement and Antidepressant Response
Change in magnetoencephalography MEG spectral power gamma power
Change in brain glutamate levels using magnetic resonance spectroscopy MRS
Change in resting and task-based functional connectivity in functional magnetic resonance imaging fMRI
Change in peripheral biomarkers
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None