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Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies (NARSAD)

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ClinicalTrials.gov Identifier: NCT03283670
Recruitment Status : Completed
First Posted : September 14, 2017
Results First Posted : April 4, 2022
Last Update Posted : April 4, 2022
Sponsor:
Collaborator:
Brain & Behavior Research Foundation
Information provided by (Responsible Party):
Ben Palanca, Washington University School of Medicine

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Depressive Disorder, Major Depressive Disorder, Treatment-Resistant Drug: Nitrous Oxide 25% Drug: Nitrous Oxide 50% Drug: Placebo Gas Phase 2

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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Each participant receives the 3 inhalation types in randomized, one hour sessions separated by at least 4 weeks
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies
Actual Study Start Date : November 22, 2016
Actual Primary Completion Date : February 18, 2020
Actual Study Completion Date : February 18, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 1. 25% nitrous oxide, 25% nitrogen, 25% oxygen
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.
 Drug: Nitrous Oxide 25%
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.
Other Name: One hour inhalation of 25% nitrous oxide
Experimental: 2. 50% nitrous oxide, 50% oxygen
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.
 Drug: Nitrous Oxide 50%
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.
Other Name: One hour inhalation of 50% nitrous oxide
Placebo Comparator: 3. Placebo gas: 50% nitrogen(inert), 50% oxygen
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.
 Drug: Placebo Gas
Placebo gas given at 50% nitrogen [inert]/50% oxygen.
Other Name: One hour inhalation of placebo gas


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Adults 18-75 years of age;
  2. Current diagnosis of unipolar major depressive disorder (MDD) without psychosis as confirmed by structured clinical interview for DSM-IV disorders;
  3. A score of >= 9 on the Montgomery-Åsberg Depression Rating Scale (MADRS);
  4. 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;
  5. Good command of the English language.

Exclusion Criteria

  1. Meets criteria for any DSM-IV diagnosis for schizophrenia, bipolar, schizoaffective, obsessive-compulsive, personality, or panic disorders;
  2. Any recent (within past 12 months) history of substance dependence or abuse (except tobacco), determined by reported history or urine drug screen;
  3. Ability to become pregnant and not using effective contraception;

  4. Contraindication against the use of nitrous oxide:

    1. Pneumothorax
    2. Bowel obstruction
    3. Middle ear occlusion
    4. Elevated intracranial pressure
    5. Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12
    6. Pregnant patients
    7. Breastfeeding women
  5. Inability to provide informed consent;
  6. Any other factor that in the investigators' judgment may affect patient safety or compliance
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03283670


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Brain & Behavior Research Foundation
Investigators
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Principal Investigator: Ben Palanca, MD Washington University School of Medicine
  Study Documents (Full-Text)

Documents provided by Ben Palanca, Washington University School of Medicine:
Study Protocol and Statistical Analysis Plan  [PDF] May 24, 2019

More Information
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Responsible Party: Ben Palanca, Associate Professor of Anesthesiology and Psychiatry, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03283670    
Other Study ID Numbers: 201608024
First Posted: September 14, 2017    Key Record Dates
Results First Posted: April 4, 2022
Last Update Posted: April 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share IPD.
Keywords provided by Ben Palanca, Washington University School of Medicine:
Depression
treatment-resistant
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Nitrous Oxide
Anesthetics, Inhalation
 Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents