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Trial record 8 of 2450 for:    NMDA

NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits

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ClinicalTrials.gov Identifier: NCT02994433
Recruitment Status : Recruiting
First Posted : December 15, 2016
Last Update Posted : July 25, 2018
Sponsor:
Information provided by (Responsible Party):
Charles Conway, Washington University School of Medicine

Brief Summary:

Most clinical major depression responds to standard treatments (medication and psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond to these treatments and are referred to as treatment-resistant major depression (TRMD). New treatments for TRMD are needed, and one promising line of research are drugs known as N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, our group demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD. This application proposes to take the next important step in understanding how nitrous oxide exerts its effects in the human brain by using state-of-the-art brain neuroimaging (functional connectivity magnetic resonance imaging) in a group of non-depressed, healthy volunteers and comparing the results to a group of TRMD patients.

This study involves exposing 20 non-depressed healthy participants and 20 TRMD participants to nitrous oxide and a placebo gas, to compare their brain images before and after each of the inhalation sessions. Sessions will be separated by at least one month to prevent treatment effects from carrying over into the following session. All willing and eligible subjects will undergo up to six functional connectivity MRI scans, and two inhalation sessions. Functional imaging in the brain will allow us to trace the interconnections between various parts of the brain, including those involved with emotion and depression.

Other procedures will involve screening materials to ensure safety of the participants before beginning the study (i.e. no MRI scan contraindications) and that subjects meet eligibility criteria to being in the targeted age range, depression/non-depressed state, neurological disorder history, and no medication exclusions.


Condition or disease Intervention/treatment Phase
Depressive Disorder, Major Depressive Disorder, Treatment-Resistant Drug: Nitrous Oxide Drug: Placebo gas Device: MRI Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits
Study Start Date : July 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nitrous Oxide
One hour inhalation of nitrous oxide
Drug: Nitrous Oxide
Nitrous oxide, an odorless, colorless gas typically used as an induction agent for general anesthesia or for dental sedation, is a known N-methyl-D-aspartate (NMDA) antagonist. It will be given at 50% nitrous oxide/50% oxygen in this study.
Other Name: laughing gas

Device: MRI
MRIs done on all participants, this is a tool we are using to measure outcomes. No treatment is from an MRI.

Placebo Comparator: Placebo Gas
One hour inhalation of placebo gas
Drug: Placebo gas
Placebo gas given at 50% nitrogen [inert]/50% oxygen.

Device: MRI
MRIs done on all participants, this is a tool we are using to measure outcomes. No treatment is from an MRI.




Primary Outcome Measures :
  1. Comparison of functional connectivity between default mode network of treatment-resistant depressed and non-depressed participants [ Time Frame: 2 hours after inhalation ]
    Functional connectivity is measured between groups after inhaling nitrous oxide/placebo using an individual seed-voxel z map and pared t-test group analysis to identify effects on inter-regional connectivity.

  2. Comparison of functional connectivity between affective network of treatment-resistant depressed and non-depressed participants [ Time Frame: 2 hours after inhalation ]
    Functional connectivity is measured between groups after inhaling nitrous oxide/placebo using an individual seed-voxel z map and pared t-test group analysis to identify effects on inter-regional connectivity.

  3. Comparison of functional connectivity between cognitive control network of treatment-resistant depressed and non-depressed participants [ Time Frame: 2 hours after inhalation ]
    Functional connectivity is measured between groups after inhaling nitrous oxide/placebo using an individual seed-voxel z map and pared t-test group analysis to identify effects on inter-regional connectivity.

  4. Comparison of functional connectivity between dorsal nexus of treatment-resistant depressed and non-depressed participants [ Time Frame: 2 hours after inhalation ]
    Functional connectivity is measured between groups after inhaling nitrous oxide/placebo using an individual seed-voxel z map and pared t-test group analysis to identify effects on inter-regional connectivity.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adults 18-65 years of age
  • Right-handed
  • Controls: Not meet The Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depressive disorder (MDD) by scoring ≤7 on the Hamilton Depression Rating Scale (HDRS), 17-item; Treatment-Resistant Major Depression (TRMD) patients: Must meet a ≥17 score on the HDRS.
  • Controls: Must not have any history of depression as determined by reported history and medical record review; TRMD: Documented (chart review) failure to respond to ≥3-4 adequate dose/duration antidepressant treatments; ≥1 in the current depressive episode.
  • Good command of the English language

Exclusion Criteria:

  • Meets criteria for any DSM-IV Axis I diagnosis as documented in medical records and as determined by structured clinical interview (except MDD for the TRMD group)
  • Known primary neurological disorders or medical disorders including dementia, stroke, encephalopathy Parkinson's Disease, brain tumors, multiple sclerosis, seizure disorder, severe cardiac or pulmonary disease
  • Any central nervous system active medication as determined by study investigator
  • Any known disease affecting drug metabolism and excretion (e.g. renal or liver disease) as determined by study investigator
  • Left-handedness
  • Not eligible for MRI scans (e.g. history of claustrophobia/implanted metal as per MRI Screening Tool)
  • Current use of psychotropic medications, antidepressants, or prescription or non-prescription drugs/herbals intended to treat depression or anxiety (control group only)
  • Any recent (within past 12 months) history of substance dependence or abuse, determined by reported history or urine drug screen
  • Ability to become pregnant and not using effective contraception
  • Contraindication against the use of nitrous oxide:

    1. Pneumothorax
    2. Bowel obstruction
    3. Middle ear occlusion
    4. Elevated intracranial pressure
    5. Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12
    6. Pregnant patients
    7. Breastfeeding women
  • Inability to provide informed consent
  • Any other factor that in the investigators' judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02994433


Contacts
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Contact: Britt Gott, MS 314-362-2463 gottb@wustl.edu
Contact: Linda Barnes 314-747-7348 barnesl@psychiatry.wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Britt Gott, MS    314-362-2463    gottb@wustl.edu   
Principal Investigator: Charles R Conway, MD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Charles R Conway, MD Washington University School of Medicine

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Responsible Party: Charles Conway, Professor of Psychiatry, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02994433     History of Changes
Other Study ID Numbers: 201606120
First Posted: December 15, 2016    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
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Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Nitrous Oxide
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents