Study Results
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Basic Information
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RECRUITING
PHASE2
172 participants
INTERVENTIONAL
2021-06-30
2026-12-01
Brief Summary
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Detailed Description
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A randomized controlled crossover feasibility study showed significant reduction in depressive symptoms at 2 and 24 hours after a single 1-hour treatment session of inhaled nitrous oxide compared with placebo. Nitrous oxide is inexpensive and can be safely administered by any trained clinician. If found to be efficacious, it could be used to provide rapid anti-depressant effect whilst the benefit of traditional anti-depressants has its delayed effect. Another potential application could be in acutely suicidal patients.
This trial will enable confirmation and extension of the findings from the feasibility study, and identify the optimal dose and regimen in a broader population of those with MDD. Participants will be randomized to receive a weekly 1-hour inhalational session of either nitrous oxide or placebo (oxygen-air mixture) for 4 weeks, and the nitrous group will be further randomly assigned to a dose of 50% or 25% nitrous oxide. Depression severity and outcomes related to treatment responses will be continuously assessed by a 'blinded-to-randomization' psychiatry (MD) rater at weekly intervals during study patient participation, using validated psychiatric diagnostics (Hamilton Depression Rating Scale-21 \[HDRS-21 or HAM-D\]; Profile of Mood States \[POMS\]; Computerized Adaptive Test-Mental Health \[CAT-MH\]; Sheehan-STS \[S-STS\]; Visual Analog Scale \[VAS\]).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Treatment; Nitrous Oxide 50% or 25%, group
Four-weekly, 60-minute inhalation sessions of 25% or 50% nitrous oxide, randomly assigned.
Nitrous oxide gas for inhalation
60-minute sessions of inhaled 50% nitrous oxide in oxygen (FiO2 0.5) or 25% nitrous oxide in oxygen (FiO2 0.75), administered weekly for 4-weeks.
Administration will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.
Control; Oxygen-air mixture, group
Four-weekly, 60-minute inhalation sessions of an oxygen and air mixture.
Placebo
60-minute sessions of inhaled oxygen-air mixture (FiO2 ≈0.3) to be administered weekly for 4-weeks.
Administration will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.
Interventions
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Nitrous oxide gas for inhalation
60-minute sessions of inhaled 50% nitrous oxide in oxygen (FiO2 0.5) or 25% nitrous oxide in oxygen (FiO2 0.75), administered weekly for 4-weeks.
Administration will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.
Placebo
60-minute sessions of inhaled oxygen-air mixture (FiO2 ≈0.3) to be administered weekly for 4-weeks.
Administration will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. DSM-5 criteria for MDD without psychosis, as determined using a structured clinical interview \[Mini International Neuropsychiatric Interview\], MDD, defined by a pre-treatment score \>16 on the HDRS-21 scale and meeting DSM-5 for MDD
Exclusion Criteria
2. Current obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses
3. Active suicidal intention, as determined by clinical interview assessment tool (Sheehan-STS) and clinical examination
4. Active or recent (\<12 months) substance use disorder; excluding nicotine
5. Administration of NMDA-antagonists (e.g., ketamine) in previous 3 months
6. Ongoing treatment with ECT
7. Presence of acute medical illness that could interfere with study participation, including significant pulmonary disease
8. Pregnancy or breastfeeding
9. Any contraindications to the use of nitrous oxide (e.g., pneumothorax, middle ear occlusion, elevated intracranial pressure, chronic cobalamin or folate deficiency unless treated with folic acid or vitamin B12).
18 Years
ALL
Yes
Sponsors
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The Alfred
OTHER
University of Chicago
OTHER
Responsible Party
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Principal Investigators
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Peter Nagele, MD, MSc
Role: PRINCIPAL_INVESTIGATOR
University of Chicago, Department of Anesthesia and Critical Care
Paul Myles, MD
Role: PRINCIPAL_INVESTIGATOR
The Alfred Hospital, Department of Anesthesiology and Perioperative Medicine
Locations
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University of Chicago Medicine
Chicago, Illinois, United States
The Alfred Hospital
Melbourne, Victoria, Australia
Countries
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Central Contacts
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Facility Contacts
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References
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Other Identifiers
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IRB18-1856
Identifier Type: -
Identifier Source: org_study_id
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