Major Depressive DisorderEarly Phase 1NCT03748446
Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder
A Early Phase 1 study testing Xenon and Nitrogen gas in people with Major Depressive Disorder and Bipolar Depression, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The investigators will test the hypothesis that inhaled xenon will produce a rapid improvement in depressive symptoms in patients suffering from treatment-resistant depression. Specifically, the investigators will conduct a parallel randomized, double-blind crossover study that will compare the effects of xenon-oxygen… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Bipolar Depression
- What is being tested?
- Xenon and Nitrogen gas
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2019to 6 Nov 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- Patient who meets DSM-V Criteria for MDD or Bipolar Depression (according to DSM-V), as the primary focus of treatment.
- Able to understand the risks and benefits of participating in this clinical trial and give informed consent, per judgment of the investigator.
- Age greater than or equal to 18 years but less than or equal to 65 years.
- Montgomery Asberg Depression Rating Scale ≥20.
- On an adequate antidepressant regimen (MDD) or on a mood stabilizing regimen (BP) that is stable for at least four weeks prior to enrollment.
- Has reliable adult transportation from and to home.
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- Has a treating psychiatrist who is in agreement with the patient's participation in the study, and aware of the safety plan in the protocol.
- No medical contraindications to receiving a xenon- or a nitrogen-oxygen mixture.
- No serious or active pulmonary disease.
Who cannot join
- MDD or BP disorder with psychosis, schizophrenia, OCD, or a primary anxiety disorder.
- Currently taking a benzodiazepine (including PRN).
- Unwilling or unable to comply with study procedures.
- Active substance abuse in the past 60 days, diagnosis of substance dependence in the past 12 months, currently active smokers of any substance, including prescription marijuana.
- Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception.
- Any unstable medical illness (cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder).
Show all 11Show fewer
- Any history of brain injury and any active state involving entrapped air/gas within a body cavity with the potential to expand causing organ distension/compression (e.g., bowel obstruction, pneumothorax, or pneumocephalus).
- History of hypersensitivity to xenon; history of multiple adverse drug reactions.
- Have taken any investigational psychotropic drug within the last 6 months.
- Inability to agree to comply with the visit schedule or study procedures.
- Not appropriate for participation in a research trial per judgment of the investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dauten Family Center for Bipolar Treatment Innovation
Boston, Massachusetts, 02114
About this study
The investigators will test the hypothesis that inhaled xenon will produce a rapid improvement in depressive symptoms in patients suffering from treatment-resistant depression. Specifically, the investigators will conduct a parallel randomized, double-blind crossover study that will compare the effects of xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) to the effects of nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group). A total of 20 severely depressed patients, 10 with major depressive disorder (MDD) and 10 with Bipolar Depression (BP), will be exposed in random order to N-TAU and X-TAU in a double-blind protocol.
Read the detailed description
Major depressive disorder (MDD) occurs in up to 17% of the population, is associated with profound dysfunction and, according to the WHO Global Burden of Disease Study, is estimated to become the second leading cause of disability worldwide by 2020. While antidepressants have proven efficacy, they usually take weeks to work and then only about a third of patients reach remission.
Beyond the traditional monoaminergic approaches, recent advances in understanding the pathophysiology of MDD have focused on the dysregulation of glutamate and associated neuronal glutaminergic associated excitotoxicity. Xenon is a potent antiglutaminergic agent that has been used as an anesthetic with minimal side effects, has neuroprotective effects consistent with antidepressants, and has the potential to be a novel antidepressant drug.
Although mania or hypomania are the defining characteristics of bipolar disorder, throughout the course of the illness depressive symptoms are more common than manic symptoms. People with bipolar disorder spend a substantial proportion of time with syndromal or subsyndromal depressive symptoms. The risk of suicide is greatly elevated during depressive episodes. Approximately 17% of people with bipolar I disorder and 24% with bipolar II disorder attempt suicide during the course of their illness. Annually around 0.4% of people with bipolar disorder will die by suicide, which is vastly greater than the international population average of 0.017%.
Pharmacological treatments are commonly used during episodes of mania and bipolar depression. Over time these episodes, particularly depression, tend to become more frequent and as repeated episodes are associated with increased functional impairment, effective treatment is a priority. The treatment of bipolar depression is quite challenging. Treatments used during acute episodes include antidepressants, some antipsychotic drugs such as quetiapine, the anticonvulsant drug lamotrigine and lithium. Response to these agents both acutely and during maintenance treatment is often partial. There are concerns about the potential for switching into mania and more frequent cycling mood with antidepressant treatment.
Only a handful of treatments are approved for bipolar depression and have been shown to be superior to placebo (lurasidone, valproate, quetiapine, the combination of fluoxetine and olanzapine, olanzapine alone, and lamotrigine), however atypical antipsychotics carry significant burden of side effects in particular metabolic.
Ketamine has been shown to be efficacious and well tolerated in MDD and BP depression, with low risk of inducing manic switch; other glutamatergic agents like memantine or lamotrigine are used as augmentation in depression and are well tolerated. Therefore, investigators believe Xenon could be well tolerated both in MDD and BP depression and possibly helpful in alleviating the symptoms.
The investigators hypothesize that patients with a primary diagnosis of depression will have a greater decrease in depressive symptoms after one session of xenon inhalation added to treatment as usual (X- TAU) compared to their session with nitrogen-oxygen inhalation added to treatment as usual (N-TAU). The investigators will specifically randomize the 20 patients to receive in random order one session of X- TAU and one session of N-TAU. Blind ratings of depression will be done with the modified Hamilton Depression Rating Scale (HDRS) and Quick Inventory of Depressive Symptomatology-Clinician Version (QIDS-C) at baseline and at predefined time intervals by clinicians experts in mood disorder who will be completely blinded to all the administration procedures.
The methods for depression assessments will be consistent with those used for the early proof-of-concept ketamine studies with assessments at 40, 80, 110, and 230 minutes post-administration and 1, 3, and 7 days post-administration. The primary outcome will be improvement at day 1. Mixed model repeated measures analysis will be used to compare the two groups.
- Conditions
- Major Depressive Disorder, Bipolar Depression
- Being tested
- Xenon, Nitrogen gas
- Medical subject headings
- Depressive Disorder, Major, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XenonDrug
The investigators have chosen to use as a maximum concentration about half the general anesthetic partial pressure of xenon (35%=70%/2) to achieve a dose that is sub-anesthetic. This concentration of xenon is very close to that at which subjects emerging from xenon anesthesia first respond to verbal commands, commonly referred to as MAC awake.
Nitrogen gasDrug
nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual
| Study group | Role | What they receive |
|---|---|---|
| X-TAU (xenon) | Active comparator | Xenon is a potent antiglutaminergic agent that has been used as an anesthetic with minimal side effects, has neuroprotective effects consistent with antidepressants and has the potential to be a novel antidepressant drug.
- xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) Receives: Drug: Xenon |
| N-TAU (nitrogen-placebo) | Placebo comparator | Nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group) Receives: Drug: Nitrogen gas |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depressive Symptoms
Hamilton Depression Rating Scale (HDRS):This scale is a 6-item survey which is one of the most frequently used instruments for evaluating depression in adults, the questionnaire allows clinicians to assess the nature and severity of mood disorders in patient populations.
Score Range: 0-42, higher scores means worse outcomes
Measured: Improvement at day 1
Depressive Symptoms
Quick Inventory of Depressive Symptomatology-Clinician Version (QIDS-C): The Quick Inventory of Depressive Symptomatology (QIDS) is designed to assess the severity of depressive symptoms. The questions to be administered by the clinician assess the severity of the nine diagnostic symptom criteria used in DSM.
Score Range: 0-48, higher scores means worse outcomes
Measured: Improvement at day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2018
- Study start5 Dec 2019
- Primary completion6 Nov 2025
- Study completion6 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- A randomized, double-blind crossover model that will compare the effects of xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) to the effects of nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group). A total of 20 severely depressed patients, 10 with major depressive disorder (MDD) and 10 with Bipolar Depression (BP), will be exposed in random order to N-TAU and X-TAU in a double-blind protocol.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew A. Nierenberg, MD, Massachusetts General Hospital
- Investigators
- Andrew Nierenberg, MD, Principal investigator, Massachussetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03748446
- Sponsor's protocol ID
- 2018P002500
- Status last verified
- Oct 2026
- First submitted
- 19 Nov 2018
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bedi A, McCarroll C, Murray JM, Stevenson MA, Fee JP. The effects of subanaesthetic concentrations of xenon in volunteers. Anaesthesia. 2002 Mar;57(3):233-41. doi: 10.1046/j.0003-2409.2001.02455.x.
PubMed 11879212Gaynes BN, Warden D, Trivedi MH, Wisniewski SR, Fava M, Rush AJ. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009 Nov;60(11):1439-45. doi: 10.1176/ps.2009.60.11.1439.
PubMed 19880458Goto T, Nakata Y, Ishiguro Y, Niimi Y, Suwa K, Morita S. Minimum alveolar concentration-awake of Xenon alone and in combination with isoflurane or sevoflurane. Anesthesiology. 2000 Nov;93(5):1188-93. doi: 10.1097/00000542-200011000-00009.
PubMed 11046204Kendall T, Morriss R, Mayo-Wilson E, Meyer TD, Jones SH, Oud M, Baker MR. NICE guidance on psychological treatments for bipolar disorder. Lancet Psychiatry. 2016 Apr;3(4):317-20. doi: 10.1016/S2215-0366(16)00082-1. No abstract available.
PubMed 27063379Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095.
PubMed 12813115Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214. doi: 10.1001/archpsyc.1994.03950030035004.
PubMed 8122957Kupfer DJ, Frank E, Phillips ML. Major depressive disorder: new clinical, neurobiological, and treatment perspectives. Lancet. 2012 Mar 17;379(9820):1045-55. doi: 10.1016/S0140-6736(11)60602-8. Epub 2011 Dec 19.
PubMed 22189047Ma D, Wilhelm S, Maze M, Franks NP. Neuroprotective and neurotoxic properties of the 'inert' gas, xenon. Br J Anaesth. 2002 Nov;89(5):739-46.
PubMed 12393773Yonas H, Grundy B, Gur D, Shabason L, Wolfson SK Jr, Cook EE. Side effects of xenon inhalation. J Comput Assist Tomogr. 1981 Aug;5(4):591-2. doi: 10.1097/00004728-198108000-00029.
PubMed 7264006
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder
- ClinicalTrials.gov ID
- NCT03748446
- Acronym / sponsor ID
- 2018P002500
- Conditions
- Major Depressive Disorder, Bipolar Depression
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 5 Dec 2019 (actual)
- Primary completion
- 6 Nov 2025 (actual)
- Study completion
- 6 Nov 2025 (actual)
- First posted
- 20 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will test the hypothesis that inhaled xenon will produce a rapid improvement in depressive symptoms in patients suffering from treatment-resistant depression. Specifically, the investigators will conduct a parallel randomized, double-blind crossover study that will compare the effects of xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) to the effects of nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group). A total of 20 severely depressed patients, 10 with major depressive disorder (MDD) and 10 with Bipolar Depression (BP), will be exposed in random order to N-TAU and X-TAU in a double-blind protocol.
Detailed description
Major depressive disorder (MDD) occurs in up to 17% of the population, is associated with profound dysfunction and, according to the WHO Global Burden of Disease Study, is estimated to become the second leading cause of disability worldwide by 2020. While antidepressants have proven efficacy, they usually take weeks to work and then only about a third of patients reach remission.
Beyond the traditional monoaminergic approaches, recent advances in understanding the pathophysiology of MDD have focused on the dysregulation of glutamate and associated neuronal glutaminergic associated excitotoxicity. Xenon is a potent antiglutaminergic agent that has been used as an anesthetic with minimal side effects, has neuroprotective effects consistent with antidepressants, and has the potential to be a novel antidepressant drug.
Although mania or hypomania are the defining characteristics of bipolar disorder, throughout the course of the illness depressive symptoms are more common than manic symptoms. People with bipolar disorder spend a substantial proportion of time with syndromal or subsyndromal depressive symptoms. The risk of suicide is greatly elevated during depressive episodes. Approximately 17% of people with bipolar I disorder and 24% with bipolar II disorder attempt suicide during the course of their illness. Annually around 0.4% of people with bipolar disorder will die by suicide, which is vastly greater than the international population average of 0.017%.
Pharmacological treatments are commonly used during episodes of mania and bipolar depression. Over time these episodes, particularly depression, tend to become more frequent and as repeated episodes are associated with increased functional impairment, effective treatment is a priority. The treatment of bipolar depression is quite challenging. Treatments used during acute episodes include antidepressants, some antipsychotic drugs such as quetiapine, the anticonvulsant drug lamotrigine and lithium. Response to these agents both acutely and during maintenance treatment is often partial. There are concerns about the potential for switching into mania and more frequent cycling mood with antidepressant treatment.
Only a handful of treatments are approved for bipolar depression and have been shown to be superior to placebo (lurasidone, valproate, quetiapine, the combination of fluoxetine and olanzapine, olanzapine alone, and lamotrigine), however atypical antipsychotics carry significant burden of side effects in particular metabolic.
Ketamine has been shown to be efficacious and well tolerated in MDD and BP depression, with low risk of inducing manic switch; other glutamatergic agents like memantine or lamotrigine are used as augmentation in depression and are well tolerated. Therefore, investigators believe Xenon could be well tolerated both in MDD and BP depression and possibly helpful in alleviating the symptoms.
The investigators hypothesize that patients with a primary diagnosis of depression will have a greater decrease in depressive symptoms after one session of xenon inhalation added to treatment as usual (X- TAU) compared to their session with nitrogen-oxygen inhalation added to treatment as usual (N-TAU). The investigators will specifically randomize the 20 patients to receive in random order one session of X- TAU and one session of N-TAU. Blind ratings of depression will be done with the modified Hamilton Depression Rating Scale (HDRS) and Quick Inventory of Depressive Symptomatology-Clinician Version (QIDS-C) at baseline and at predefined time intervals by clinicians experts in mood disorder who will be completely blinded to all the administration procedures.
The methods for depression assessments will be consistent with those used for the early proof-of-concept ketamine studies with assessments at 40, 80, 110, and 230 minutes post-administration and 1, 3, and 7 days post-administration. The primary outcome will be improvement at day 1. Mixed model repeated measures analysis will be used to compare the two groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized, double-blind crossover model that will compare the effects of xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) to the effects of nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group). A total of 20 severely depressed patients, 10 with major depressive disorder (MDD) and 10 with Bipolar Depression (BP), will be exposed in random order to N-TAU and X-TAU in a double-blind protocol.
| Arm | Type | Receives |
|---|---|---|
| X-TAU (xenon) | Active comparator | Drug: XenonXenon is a potent antiglutaminergic agent that has been used as an anesthetic with minimal side effects, has neuroprotective effects consistent with antidepressants and has the potential to be a novel antidepressant drug. - xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) |
| N-TAU (nitrogen-placebo) | Placebo comparator | Drug: Nitrogen gasNitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient who meets DSM-V Criteria for MDD or Bipolar Depression (according to DSM-V), as the primary focus of treatment.
- Able to understand the risks and benefits of participating in this clinical trial and give informed consent, per judgment of the investigator.
- Age greater than or equal to 18 years but less than or equal to 65 years.
- Montgomery Asberg Depression Rating Scale ≥20.
- On an adequate antidepressant regimen (MDD) or on a mood stabilizing regimen (BP) that is stable for at least four weeks prior to enrollment.
Key exclusion criteria (11 listed)
- MDD or BP disorder with psychosis, schizophrenia, OCD, or a primary anxiety disorder.
- Currently taking a benzodiazepine (including PRN).
- Unwilling or unable to comply with study procedures.
- Active substance abuse in the past 60 days, diagnosis of substance dependence in the past 12 months, currently active smokers of any substance, including prescription marijuana.
- Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception.
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 |
|---|---|---|
| XenonThe investigators have chosen to use as a maximum concentration about half the general anesthetic partial pressure of xenon (35%=70%/2) to achieve a dose that is sub-anesthetic. This concentration of xenon is very close to that at which subjects emerging from xenon anesthesia first respond to verbal commands, commonly referred to as MAC awake. | Drug | X-TAU (xenon) |
| Nitrogen gasnitrogen-oxygen (35:65 ratio by volume) added to treatment as usual | Drug | N-TAU (nitrogen-placebo) |
Primary outcome
Depressive Symptoms
Time frame: Improvement at day 1
Hamilton Depression Rating Scale (HDRS):This scale is a 6-item survey which is one of the most frequently used instruments for evaluating depression in adults, the questionnaire allows clinicians to assess the nature and severity of mood disorders in patient populations. Score Range: 0-42, higher scores means worse outcomes
Depressive Symptoms
Time frame: Improvement at day 1
Quick Inventory of Depressive Symptomatology-Clinician Version (QIDS-C): The Quick Inventory of Depressive Symptomatology (QIDS) is designed to assess the severity of depressive symptoms. The questions to be administered by the clinician assess the severity of the nine diagnostic symptom criteria used in DSM. Score Range: 0-48, higher scores means worse outcomes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Background: PubMed 11879212Bedi A, McCarroll C, Murray JM, Stevenson MA, Fee JP. The effects of subanaesthetic concentrations of xenon in volunteers. Anaesthesia. 2002 Mar;57(3):233-41. doi: 10.1046/j.0003-2409.2001.02455.x.
- Background: PubMed 19880458Gaynes BN, Warden D, Trivedi MH, Wisniewski SR, Fava M, Rush AJ. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009 Nov;60(11):1439-45. doi: 10.1176/ps.2009.60.11.1439.
- Background: PubMed 11046204Goto T, Nakata Y, Ishiguro Y, Niimi Y, Suwa K, Morita S. Minimum alveolar concentration-awake of Xenon alone and in combination with isoflurane or sevoflurane. Anesthesiology. 2000 Nov;93(5):1188-93. doi: 10.1097/00000542-200011000-00009.
- Background: PubMed 27063379Kendall T, Morriss R, Mayo-Wilson E, Meyer TD, Jones SH, Oud M, Baker MR. NICE guidance on psychological treatments for bipolar disorder. Lancet Psychiatry. 2016 Apr;3(4):317-20. doi: 10.1016/S2215-0366(16)00082-1. No abstract available.
- Background: PubMed 12813115Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095.
- Background: PubMed 8122957Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214. doi: 10.1001/archpsyc.1994.03950030035004.
- Background: PubMed 22189047Kupfer DJ, Frank E, Phillips ML. Major depressive disorder: new clinical, neurobiological, and treatment perspectives. Lancet. 2012 Mar 17;379(9820):1045-55. doi: 10.1016/S0140-6736(11)60602-8. Epub 2011 Dec 19.
- Background: PubMed 12393773Ma D, Wilhelm S, Maze M, Franks NP. Neuroprotective and neurotoxic properties of the 'inert' gas, xenon. Br J Anaesth. 2002 Nov;89(5):739-46.
- Background: PubMed 7264006Yonas H, Grundy B, Gur D, Shabason L, Wolfson SK Jr, Cook EE. Side effects of xenon inhalation. J Comput Assist Tomogr. 1981 Aug;5(4):591-2. doi: 10.1097/00004728-198108000-00029.
- Individual participant dataSharing planned: No
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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.
Andrew Nierenberg, MD principal investigator
Massachussetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Xenon and Nitrogen gas in people with Major Depressive Disorder and Bipolar Depression, run by Massachusetts General Hospital 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 9 inclusion and 11 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 9 Oct 2026. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Depressive Symptoms (time frame: Improvement at day 1). The study lists 2 primary outcomes in all. 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 NCT03748446, which also lists 9 linked publications.
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 9 Oct 2026.