NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits
| Status: | Recruiting |
|---|---|
| Conditions: | Depression, Depression, Major Depression Disorder (MDD) |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 7/27/2018 |
| Start Date: | July 2016 |
| End Date: | June 2019 |
| Contact: | Britt Gott, MS |
| Email: | gottb@wustl.edu |
| Phone: | 314-362-2463 |
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.
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.
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).
We found this trial at
1
site
660 S Euclid Ave
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Charles R Conway, MD
Phone: 314-362-2463
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
Click here to add this to my saved trials
