Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder

NCT03748446 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 2018P002500
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Major Depressive Disorder; Bipolar Depression

Outcome Measures

Primary Outcomes (2)

• 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

  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

  Improvement at day 1

Study Arms (2)

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)

Drug: Xenon

N-TAU (nitrogen-placebo)

PLACEBO COMPARATOR

Nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group)

Drug: Nitrogen gas

Interventions

Xenon DRUG

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.

X-TAU (xenon)

Nitrogen gas DRUG

nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual

N-TAU (nitrogen-placebo)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Dauten Family Center for Bipolar Treatment Innovation

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (9)

• 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.

  PMID: 11879212 BACKGROUND

• Gaynes 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.

  PMID: 19880458 BACKGROUND

• Goto 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.

  PMID: 11046204 BACKGROUND

• Kendall 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.

  PMID: 27063379 BACKGROUND

• Kessler 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.

  PMID: 12813115 BACKGROUND

• Krystal 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.

  PMID: 8122957 BACKGROUND

• Kupfer 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.

  PMID: 22189047 BACKGROUND

• Ma 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.

  PMID: 12393773 BACKGROUND

• Yonas 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.

  PMID: 7264006 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Bipolar Disorder

Interventions

Xenon; Nitrogen

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Noble Gases; Elements; Inorganic Chemicals; Gases

Study Officials

• Andrew Nierenberg, MD

  Massachussetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Selen Amado, BA

CONTACT

6177267591; samado2@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The identity of the inhalant will be blinded to all except the anesthesiologist, who will not participate in any assessment of the depressive symptoms.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: 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.

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 20, 2018
• Study Start: December 5, 2019
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)