Depressive Disorder, MajorPhase 2NARSADNCT03283670
Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies
A Phase 2 study testing Nitrous Oxide 25% and Nitrous Oxide 50% in people with Depressive Disorder, Major and Depressive Disorder, Treatment-Resistant, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of the study aims to determine whether different concentrations of nitrous oxide (N2O) have different antidepressant effects for adults with treatment-resistant major depression. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant
- What is being tested?
- Nitrous Oxide 25% and Nitrous Oxide 50%
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Nov 2016to 18 Feb 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults 18-75 years of age;
- Current diagnosis of unipolar major depressive disorder (MDD) without psychosis as confirmed by structured clinical interview for DSM-IV disorders;
- A score of >= 9 on the Montgomery-Åsberg Depression Rating Scale (MADRS);
- Documented (i.e., chart review) lifetime failure to respond to >=3 adequate dose/duration antidepressant treatment trials, ≥1 medication failure in the current depressive episode;
- Good command of the English language.
Who cannot join
- Meets criteria for any DSM-IV diagnosis for schizophrenia, bipolar, schizoaffective, obsessive-compulsive, personality, or panic disorders;
- Any recent (within past 12 months) history of substance dependence or abuse (except tobacco), determined by reported history or urine drug screen;
- Ability to become pregnant and not using effective contraception;
- Contraindication against the use of nitrous oxide:
- Pneumothorax
- Bowel obstruction
Show all 13Show fewer
- Middle ear occlusion
- Elevated intracranial pressure
- Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12
- Pregnant patients
- Breastfeeding women
- Inability to provide informed consent;
- Any other factor that in the investigators' judgment may affect patient safety or compliance
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
The purpose of the study aims to determine whether different concentrations of nitrous oxide (N2O) have different antidepressant effects for adults with treatment-resistant major depression.
Read the detailed description
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.
All patients will receive 3 randomized, one hour nitrous oxide inhalations to placebo (0% N2O), low dose (25% N2O), and high dose (50% N2O). Inhalation sessions will be at least 4 weeks apart. Mood will be assessed at baseline, 2 and 24 hours, and 1, 2, and 4 weeks post-inhalation for each dose.
- Being tested
- Nitrous Oxide 25%, Nitrous Oxide 50%, Placebo Gas
- Keywords
- Depression, treatment-resistant
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous Oxide 25%Drug
Also called One hour inhalation of 25% 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 a concentration of 25% nitrous oxide/50% oxygen/25% nitrogen.
Nitrous Oxide 50%Drug
Also called One hour inhalation of 50% 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 a concentration of 50% nitrous oxide/50% oxygen.
Placebo GasDrug
Also called One hour inhalation of placebo gas
Placebo gas given at 50% nitrogen [inert]/50% oxygen.
| Study group | Role | What they receive |
|---|---|---|
| 1. 25% nitrous oxide, 25% nitrogen, 25% oxygen | Experimental | Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned. Receives: Drug: Nitrous Oxide 25% |
| 2. 50% nitrous oxide, 50% oxygen | Experimental | Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned. Receives: Drug: Nitrous Oxide 50% |
| 3. Placebo gas: 50% nitrogen(inert), 50% oxygen | Placebo comparator | Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned. Receives: Drug: Placebo Gas |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Depression Symptoms Measured by the Hamilton Depression Rating Scale- 21 Items
Change in depression symptoms measured by the Hamilton Depression Rating Scale- 21 items. The HAMD-21 is designed to rate the severity of depression in patients. Although it contains 21 areas, calculate the patient's score as the total score on the first 17 answers. Scale: 0=absent, 4=worst level possible) the scores on the individual items are summed. Changes will be based on measurements obtained at baseline, approximately 2 hours after inhalation, and approximately 24 hours after inhalation. Changes are based on subtracti on of baseline score.
Measured: 2 and 24 hours after inhalation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2017
- Study start22 Nov 2016
- Primary completion18 Feb 2020
- Study completion18 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each participant receives the 3 inhalation types in randomized, one hour sessions separated by at least 4 weeks
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Brain & Behavior Research Foundation
- Responsible party
- Principal investigator, Ben Palanca, Washington University School of Medicine
- Investigators
- Ben Palanca, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03283670
- Sponsor's protocol ID
- 201608024
- Acronym
- NARSAD
- Status last verified
- Mar 2022
- First submitted
- 9 Nov 2016
- Last updated
- 4 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: There is no plan to share IPD.
Publications
de Leon VC, Kumar A, Nagele P, Palanca BJ, Gott B, Janski A, Zorumski CF, Conway CR. Nitrous Oxide Reduced Suicidal Ideation in Treatment-Resistant Major Depression in Exploratory Analysis. J Clin Psychiatry. 2023 Aug 16;84(5):22br14725. doi: 10.4088/JCP.22br14725. No abstract available.
PubMed 37585253
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies
- ClinicalTrials.gov ID
- NCT03283670
- Acronym / sponsor ID
- NARSAD / 201608024
- Keywords
- Depression, treatment-resistant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Brain & Behavior Research Foundation
- Study start
- 22 Nov 2016 (actual)
- Primary completion
- 18 Feb 2020 (actual)
- Study completion
- 18 Feb 2020 (actual)
- First posted
- 14 Sep 2017 (actual)
- Results
- Posted 4 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study aims to determine whether different concentrations of nitrous oxide (N2O) have different antidepressant effects for adults with treatment-resistant major depression.
Detailed description
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.
All patients will receive 3 randomized, one hour nitrous oxide inhalations to placebo (0% N2O), low dose (25% N2O), and high dose (50% N2O). Inhalation sessions will be at least 4 weeks apart. Mood will be assessed at baseline, 2 and 24 hours, and 1, 2, and 4 weeks post-inhalation for each dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- Model description
- Each participant receives the 3 inhalation types in randomized, one hour sessions separated by at least 4 weeks
| Arm | Type | Receives |
|---|---|---|
| 1. 25% nitrous oxide, 25% nitrogen, 25% oxygen | Experimental | Drug: Nitrous Oxide 25%Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned. |
| 2. 50% nitrous oxide, 50% oxygen | Experimental | Drug: Nitrous Oxide 50%Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned. |
| 3. Placebo gas: 50% nitrogen(inert), 50% oxygen | Placebo comparator | Drug: Placebo GasParticipants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults 18-75 years of age;
- Current diagnosis of unipolar major depressive disorder (MDD) without psychosis as confirmed by structured clinical interview for DSM-IV disorders;
- A score of >= 9 on the Montgomery-Åsberg Depression Rating Scale (MADRS);
- Documented (i.e., chart review) lifetime failure to respond to >=3 adequate dose/duration antidepressant treatment trials, ≥1 medication failure in the current depressive episode;
- Good command of the English language.
Key exclusion criteria (13 listed)
- Meets criteria for any DSM-IV diagnosis for schizophrenia, bipolar, schizoaffective, obsessive-compulsive, personality, or panic disorders;
- Any recent (within past 12 months) history of substance dependence or abuse (except tobacco), determined by reported history or urine drug screen;
- Ability to become pregnant and not using effective contraception;
- Contraindication against the use of nitrous oxide:
- Inability to provide informed consent;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitrous Oxide 25%Also: One hour inhalation of 25% nitrous oxideNitrous 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 a concentration of 25% nitrous oxide/50% oxygen/25% nitrogen. | Drug | 1. 25% nitrous oxide, 25% nitrogen, 25% oxygen |
| Nitrous Oxide 50%Also: One hour inhalation of 50% nitrous oxideNitrous 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 a concentration of 50% nitrous oxide/50% oxygen. | Drug | 2. 50% nitrous oxide, 50% oxygen |
| Placebo GasAlso: One hour inhalation of placebo gasPlacebo gas given at 50% nitrogen [inert]/50% oxygen. | Drug | 3. Placebo gas: 50% nitrogen(inert), 50% oxygen |
Primary outcome
Change in Depression Symptoms Measured by the Hamilton Depression Rating Scale- 21 Items
Time frame: 2 and 24 hours after inhalation
Change in depression symptoms measured by the Hamilton Depression Rating Scale- 21 items. The HAMD-21 is designed to rate the severity of depression in patients. Although it contains 21 areas, calculate the patient's score as the total score on the first 17 answers. Scale: 0=absent, 4=worst level possible) the scores on the individual items are summed. Changes will be based on measurements obtained at baseline, approximately 2 hours after inhalation, and approximately 24 hours after inhalation. Changes are based on subtracti on of baseline score.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37585253de Leon VC, Kumar A, Nagele P, Palanca BJ, Gott B, Janski A, Zorumski CF, Conway CR. Nitrous Oxide Reduced Suicidal Ideation in Treatment-Resistant Major Depression in Exploratory Analysis. J Clin Psychiatry. 2023 Aug 16;84(5):22br14725. doi: 10.4088/JCP.22br14725. No abstract available.
- Individual participant dataSharing planned: No. There is no plan to share IPD.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ben Palanca, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitrous Oxide 25% and Nitrous Oxide 50% in people with Depressive Disorder, Major and Depressive Disorder, Treatment-Resistant, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Depression Symptoms Measured by the Hamilton Depression Rating Scale- 21 Items (time frame: 2 and 24 hours after inhalation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03283670, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2022.