Ignite Creation Date:
2024-05-06 @ 2:48 AM
Last Modification Date:
2024-10-26 @ 11:23 AM
Study NCT ID:
NCT02122562
Status:
RECRUITING
Last Update Posted:
2024-06-06
First Post:
2014-04-23
Brief Title:
Ketamine Alcohol in Treatment-Resistant Depression
Sponsor:
Mark Niciu
Organization:
University of Iowa
Study Overview
Official Title:
Functional Neuroimaging of the Enhanced Antidepressant Efficacy of Ketamine in a Biologically-Enriched Subgroup
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
A single subanesthetic dose infusion of the N-methyl-D-aspartate NMDA receptor antagonist ketamine has rapid and robust antidepressant effects in patients with treatment-refractory major depressive disorder TRD A family history of an alcohol use disorder Family History Positive FHP is one of the strongest identified predictors of an improved antidepressant response to ketamine Like ketamine alcohol is a functional NMDA receptor antagonist FHP is associated with differential response to ketamine eg blunted psychotomimetic side effects One of the primary mechanistic hypotheses for ketamines antidepressant action is the acute intrasynaptic release of glutamate from major output neurons eg cortical pyramidal cells Preliminary clinical studies have demonstrated this acute glutamate surge in response to subanesthetic dose ketamine Based on these findings the investigators hypothesize that ketamines enhanced antidepressant efficacy in FHP TRD subjects is at least in part attributable to increased glutamate release relative to TRD subjects without a family history of alcohol use disorder Family History Negative FHN To test this hypothesis the investigators have designed a now two-site open-label study of 18-55-year-old medically and neurologically healthy currently moderately-to-severely depressed TRD patients In total the investigators plan to recruit 25 FHP and 25 FHN TRD subjects All subjects must not have a current substance use disorder except nicotine or caffeine The experimental portion consists of two phases The preliminary first phase is a medication taper if needed and psychotropic medication-free period The experimental second phase comprises one subanesthetic dose 05mgkg x 40 minute ketamine infusion The ketamine infusion will occur during 7T-magnetic resonance imaging MRI both resting-state functional MRI rs-fMRI and magnetic resonance spectroscopy MRS to detect glutamate in the ventromedial prefrontal cortexventral anterior cingulate cortex vmPFCvACC The primary outcome measure is group mean change in Montgomery-Åsberg Depression Rating Scale MADRS score from pre-ketamine infusion baseline to one-week post-infusion where the investigators observed ketamines greatest antidepressant effect in FHP TRD Additional outcome measures are vmPFCvACC glutamate change in response to ketamine based on family history status In summary this study will provide key mechanistic information on ketamines improved antidepressant efficacy in a biologically-enriched subgroup This will contribute to the systematic development of more efficacious personalized treatments for major depression in an effort to reduce its enormous public health burden
Detailed Description:
Objective
Glutamate-based medications including the glutamate modulator ketamine result in rapid robust and sustained typically up to one week antidepressant effects in randomized controlled trials in treatment-refractory unipolar and bipolar depression Previous work by the investigators group has demonstrated that a family history of alcohol dependence predicts a more robust antidepressant response to ketamine in both treatment-resistant unipolar and bipolar depression
Recently-detoxified alcoholics and affected first-degree relatives display blunted psychotomimetic cognitive and other neuropsychiatric effects when administered a subanesthetic dose of ketamine Based on the prior post hoc results the investigators seek to prospectively demonstrate that a family history of an alcohol use disorder predicts a more robust antidepressant response to ketamine
Study Population
18-55 year old TRD without psychotic features patients in a current major depressive episode of at least moderate severity will be recruited and enrolled in this study All subjects must not have a current substance use disorder except nicotine or caffeine All subjects must be psychotropic medication-free for at least two weeks prior to the ketamine infusion The targeted number of completers is 50 depressed subjects 60 signing consent to account for attrition 25 FHP subjects as defined by either one first degree relative or two second-degree relatives with an alcohol user disorder on the Family Interview for Genetics Studies FIGS and Family Tree Questionnaire FTQ and 25 FHN negative subjects
Design
This study is currently a single site open-label protocol in psychotropic medication-free depressed subjects This protocol consists of two phases Phase I consists of a medication taper if needed and at least two week drug-free period Phase II includes a subanestheticantidepressant dose ketamine infusion during 7T-MRI
Outcome Measures
The primary hypothesisoutcome measure will be mean change in MADRS total score from the pre-ketamine infusion baseline to 7 days post-infusion between the FHP and FHN groups Other exploratory measures include glutamate alterations during intravenous ketamine infusions and rs-fMRI as a function of family history status
Glutamate-based medications including the glutamate modulator ketamine result in rapid robust and sustained typically up to one week antidepressant effects in randomized controlled trials in treatment-refractory unipolar and bipolar depression Previous work by the investigators group has demonstrated that a family history of alcohol dependence predicts a more robust antidepressant response to ketamine in both treatment-resistant unipolar and bipolar depression
Recently-detoxified alcoholics and affected first-degree relatives display blunted psychotomimetic cognitive and other neuropsychiatric effects when administered a subanesthetic dose of ketamine Based on the prior post hoc results the investigators seek to prospectively demonstrate that a family history of an alcohol use disorder predicts a more robust antidepressant response to ketamine
Study Population
18-55 year old TRD without psychotic features patients in a current major depressive episode of at least moderate severity will be recruited and enrolled in this study All subjects must not have a current substance use disorder except nicotine or caffeine All subjects must be psychotropic medication-free for at least two weeks prior to the ketamine infusion The targeted number of completers is 50 depressed subjects 60 signing consent to account for attrition 25 FHP subjects as defined by either one first degree relative or two second-degree relatives with an alcohol user disorder on the Family Interview for Genetics Studies FIGS and Family Tree Questionnaire FTQ and 25 FHN negative subjects
Design
This study is currently a single site open-label protocol in psychotropic medication-free depressed subjects This protocol consists of two phases Phase I consists of a medication taper if needed and at least two week drug-free period Phase II includes a subanestheticantidepressant dose ketamine infusion during 7T-MRI
Outcome Measures
The primary hypothesisoutcome measure will be mean change in MADRS total score from the pre-ketamine infusion baseline to 7 days post-infusion between the FHP and FHN groups Other exploratory measures include glutamate alterations during intravenous ketamine infusions and rs-fMRI as a function of family history status
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 14-M-0085 | OTHER | National Institutes of Health | None |