Ketamine Alcohol (in Treatment-Resistant Depression)

Part of paid clinical trials in Iowa City, Iowa.

Sponsor
Mark Niciu
Study ID
NCT02122562
Phase
PHASE2
Status
Recruiting
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Conditions

  • Alcoholism
  • Magnetic Resonance Imaging
  • Major Depression

Eligibility Criteria

Sex
ALL
Age
18 Years - 55 Years
Healthy Volunteers
Not accepted

Interventions

  • Ketamine — DRUG
    Treatment

Study Details

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, e.g. blunted psychotomimetic side effects. One of the primary mechanistic hypotheses for ketamine's antidepressant action is the acute intrasynaptic release of glutamate from major output neurons, e.g. 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 ketamine's 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 (0.5mg/kg 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 cortex/ventral anterior cingulate cortex (vmPFC/vACC). 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 ketamine's greatest antidepressant effect in FHP TRD. Additional outcome measures are vmPFC/vACC glutamate change in response to ketamine based on family history status. In summary, this study will provide key mechanistic information on ketamine's 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.

Key Dates

Start date
Apr 23, 2014
Status verified
Apr 2026
Primary completion
Sep 30, 2028
Completion
Sep 30, 2028

Study Design

Enrollment
60 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Ketamine
    Ketamine 0.5 mg/mL IV (infused over 40 minutes)

Primary Outcome Measure

Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Pre-ketamine (baseline) to one week post-ketamine infusion ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of Iowa Health CareIowa CityIowa52242
Osura R Amarajeewa, M.B.B.S.
[email protected]
319-353-8536
Mark J Niciu, M.D. Ph.D.
[email protected]
319-356-1549

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University of Iowa Health Care· Iowa City, IA

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