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RecruitingPhase 1

NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 65 Years
Sex
All sexes
Healthy volunteers
Accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: MRI scans

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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."
  • "All willing and eligible subjects will undergo up to six functional connectivity MRI scans, and two inhalation sessions."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests how nitrous oxide gas affects brain areas linked to feelings and depression. It is for healthy adults without depression and adults whose depression has not improved with treatment. Participants breathe nitrous oxide and a placebo gas for comparison at separate visits and have up to six MRI brain scans.

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 approximately 25 non-depressed healthy participants and 25 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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • You are 18–65 years old.
  • You are right-handed.
  • You understand English well.
  • Healthy group: You have never had depression and score 7 or less on a depression rating test.
  • Depression group: You have major depression and score 17 or more on a depression rating test.
  • Depression group: Medical records show that at least 3–4 antidepressant treatments did not help despite enough medicine and treatment time. At least one was during your current period of depression.

Who can't join

  • You have another mental health condition covered by the study’s rules. Major depression is allowed only in the depression group.
  • You have a brain or nerve disorder, such as dementia, stroke, Parkinson’s disease, a brain tumor, multiple sclerosis, or seizures; or severe heart or lung disease.
  • You take medicine that affects the brain or nervous system, or have a disease that affects how your body handles medicines, as judged by the study doctor. Healthy volunteers also cannot use medicines or herbs for depression or anxiety.
  • You cannot safely have an MRI, such as because of certain metal implants or fear of enclosed spaces.
  • You have had problems with drug or alcohol abuse or dependence in the past 12 months.
  • You are pregnant, breastfeeding, or able to become pregnant but are not using effective birth control.
  • Nitrous oxide is unsafe for you because of a collapsed lung, blocked bowel or middle ear, high pressure inside the skull, or long-term low vitamin B12 or folate treated with these vitamins.
  • You cannot give informed consent, meaning you cannot understand and agree to take part, or the study team has other concerns about your safety or ability to follow study steps.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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).

Study sites (1)

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