DepressionPhase 2NCT02139540
Nitrous Oxide as Treatment for Major Depression - a Pilot Study
A Phase 2 study testing Nitrous Oxide in people with Depression and Major Depressive Disorder, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Major depressive disorder (MDD) is a global medical problem with significant shortcomings in current therapy. Chief among these is the delay between initiation of pharmacologic therapy and clinical improvement in symptoms. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Major Depressive Disorder
- What is being tested?
- Nitrous Oxide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to Apr 2015
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults 18-65 years of age
- Major depressive disorder without psychosis with as determined by structured interview using the Mini-International Neuropsychiatric Interview (MINI).
- (baseline )
- HDRS-21 score of >18
- Good command of the English language
Who cannot join
- History of:
- Bipolar disorder
- Schizoprenia
- Schizoaffective disorder
- Obsessive-compulsive disorder, panic disorder
- Substance abuse or dependence (except for remote substance abuse or dependence with remission at least 1 year prior to the study and except for nicotine use disorders)
Show all 22Show fewer
- Axis II diagnoses that may interfere with the patient's ability to improve on nitrous oxide
- Acute medical illness that may pose subject at risk during nitrous oxide administration
- Active suicidal intention (inability to contract for safety)
- Active psychotic symptoms
- Patients with significant pulmonary disease and/or requiring supplemental oxygen
- Contraindication against the use of nitrous oxide:
- Pneumothorax
- Bowel obstruction
- Middle ear occlusion
- Elevated intracranial pressure
- Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12
- Pregnant patients
- Breastfeeding women
- Previous administration of NMDA-receptor antagonists (e.g., ketamine) within the last 3 months
- Current electro-convulsive therapy treatment
- Any active suicidal ideation, intention, or planning (clinical assessment of suicidality will be used)
Trial locations and contacts
1 site in 1 country.
About this study
Major depressive disorder (MDD) is a global medical problem with significant shortcomings in current therapy. Chief among these is the delay between initiation of pharmacologic therapy and clinical improvement in symptoms. Recently ketamine, an NDMA-receptor antagonist has been shown to rapidly and effectively reverse the symptoms of MDD. Nitrous oxide, another NMDA-receptor antagonist, may produce the same effect with a cleaner side-effect profile and perhaps without the need for intravenous access and anesthesia personnel. Therefore, we propose conducting a pilot randomized placebo controlled double-blind crossover study in which patients will receive up to 50% nitrous oxide in oxygen or up to 50% oxygen in air for a period of one hour in addition to standard medical therapy. Depression severity will be assessed by a blinded observer pre-treatment, 30 minutes and 2 hours post treatment using the Hamilton depression rating scale.
Read the detailed description
We will study 20 patients with non-treatment resistant major depression and 20 patients with treatment-resistant major depression, defined as failure of at least 2 antidepressants in the current depressive episode and 3 lifetime medication failures.
- Conditions
- Depression, Major Depressive Disorder
- Being tested
- Nitrous Oxide, Placebo
- Keywords
- Treatment
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous OxideDrug
Also called Laughing Gas
Patients will receive either up to 50% nitrous oxide/50% oxygen for 1 hour or "placebo" (50% nitrogen [inert]/50% oxygen) in two separate sessions. Both sessions will be 1 week apart.
PlaceboDrug
Also called 50% nitrogen [inert]/50% oxygen
50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup
| Study group | Role | What they receive |
|---|---|---|
| N2O/Placebo | Other | First session: Nitrous oxide Second session: placebo Receives: Drug: Nitrous Oxide; Drug: Placebo |
| Placebo/N2O | Other | First session: Placebo Second session: Nitrous Oxide Receives: Drug: Nitrous Oxide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hamilton Depression Rating Scale HDRS-21
(21-point Hamilton Depression Rating Scale) Scoring is based on the first 17 items on the 21 point scale. Eight items are scored on a 5-point scale, ranging form 0=not present to 4= severe. Nine are scored from 0-2.
Measured: baseline and 24 hours
Secondary outcomes (1)
Change in Quick Inventory of Depressive Symptomatology - Self Report - QIDS -SR
[Quick Inventory of Depressive Symptomatology - Self Report] An item-by-item severity scale of 0 to 3, with possible total scores ranging from 0 to 84. The items on the scale are added together for a total score. Higher scores mean worse outcome.
Measured: baseline and 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2014 (estimated)
- Study startNov 2012
- Primary completionApr 2015
- Study completionApr 2015
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 DepressionStudies 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Nagele, MD, MSc, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02139540
- Sponsor's protocol ID
- 201204023
- Status last verified
- Jan 2020
- First submitted
- 13 May 2014
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrous Oxide as Treatment for Major Depression - a Pilot Study
- ClinicalTrials.gov ID
- NCT02139540
- Acronym / sponsor ID
- 201204023
- Conditions
- Depression, Major Depressive Disorder
- Keywords
- Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Nov 2012 (actual)
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 15 May 2014 (estimated)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Major depressive disorder (MDD) is a global medical problem with significant shortcomings in current therapy. Chief among these is the delay between initiation of pharmacologic therapy and clinical improvement in symptoms. Recently ketamine, an NDMA-receptor antagonist has been shown to rapidly and effectively reverse the symptoms of MDD. Nitrous oxide, another NMDA-receptor antagonist, may produce the same effect with a cleaner side-effect profile and perhaps without the need for intravenous access and anesthesia personnel. Therefore, we propose conducting a pilot randomized placebo controlled double-blind crossover study in which patients will receive up to 50% nitrous oxide in oxygen or up to 50% oxygen in air for a period of one hour in addition to standard medical therapy. Depression severity will be assessed by a blinded observer pre-treatment, 30 minutes and 2 hours post treatment using the Hamilton depression rating scale.
Detailed description
We will study 20 patients with non-treatment resistant major depression and 20 patients with treatment-resistant major depression, defined as failure of at least 2 antidepressants in the current depressive episode and 3 lifetime medication failures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N2O/Placebo | Other | Drug: Nitrous Oxide, Drug: PlaceboFirst session: Nitrous oxide Second session: placebo |
| Placebo/N2O | Other | Drug: Nitrous Oxide, Drug: PlaceboFirst session: Placebo Second session: Nitrous Oxide |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults 18-65 years of age
- Major depressive disorder without psychosis with as determined by structured interview using the Mini-International Neuropsychiatric Interview (MINI).
- (baseline )
- HDRS-21 score of >18
- Good command of the English language
Key exclusion criteria (22 listed)
- Bipolar disorder
- Schizoprenia
- Schizoaffective disorder
- Obsessive-compulsive disorder, panic disorder
- Substance abuse or dependence (except for remote substance abuse or dependence with remission at least 1 year prior to the study and except for nicotine use disorders)
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 OxideAlso: Laughing GasPatients will receive either up to 50% nitrous oxide/50% oxygen for 1 hour or "placebo" (50% nitrogen [inert]/50% oxygen) in two separate sessions. Both sessions will be 1 week apart. | Drug | N2O/Placebo, Placebo/N2O |
| PlaceboAlso: 50% nitrogen [inert]/50% oxygen50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup | Drug | N2O/Placebo, Placebo/N2O |
Primary outcome
Change in Hamilton Depression Rating Scale HDRS-21
Time frame: baseline and 24 hours
(21-point Hamilton Depression Rating Scale) Scoring is based on the first 17 items on the 21 point scale. Eight items are scored on a 5-point scale, ranging form 0=not present to 4= severe. Nine are scored from 0-2.
1 secondary outcome
Change in Quick Inventory of Depressive Symptomatology - Self Report - QIDS -SR
Time frame: baseline and 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- 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.
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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.
Peter Nagele, MD, MSc 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 in people with Depression and Major Depressive Disorder, 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 22 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 27 Jan 2020. 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. 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 27 Jan 2020). 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 Hamilton Depression Rating Scale HDRS-21 (time frame: baseline and 24 hours). 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 NCT02139540, 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 27 Jan 2020.