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

Primary Purpose

Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nitrous Oxide 25%
Nitrous Oxide 50%
Placebo Gas
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depressive Disorder, Major focused on measuring Depression, treatment-resistant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

1. 25% nitrous oxide, 25% nitrogen, 25% oxygen

2. 50% nitrous oxide, 50% oxygen

3. Placebo gas: 50% nitrogen(inert), 50% oxygen

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
November 9, 2016
Last Updated
March 28, 2022
Sponsor
Washington University School of Medicine
Collaborators
Brain & Behavior Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT03283670
Brief Title
Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies
Acronym
NARSAD
Official Title
Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
November 22, 2016 (Actual)
Primary Completion Date
February 18, 2020 (Actual)
Study Completion Date
February 18, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Washington University School of Medicine
Collaborators
Brain & Behavior Research Foundation

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant
Keywords
Depression, treatment-resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Each participant receives the 3 inhalation types in randomized, one hour sessions separated by at least 4 weeks
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1. 25% nitrous oxide, 25% nitrogen, 25% oxygen
Arm Type
Experimental
Arm Description
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.
Arm Title
2. 50% nitrous oxide, 50% oxygen
Arm Type
Experimental
Arm Description
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.
Arm Title
3. Placebo gas: 50% nitrogen(inert), 50% oxygen
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Nitrous Oxide 25%
Other Intervention Name(s)
One hour inhalation of 25% nitrous oxide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Nitrous Oxide 50%
Other Intervention Name(s)
One hour inhalation of 50% nitrous oxide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo Gas
Other Intervention Name(s)
One hour inhalation of placebo gas
Intervention Description
Placebo gas given at 50% nitrogen [inert]/50% oxygen.
Primary Outcome Measure Information:
Title
Change in Depression Symptoms Measured by the Hamilton Depression Rating Scale- 21 Items
Description
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.
Time Frame
2 and 24 hours after inhalation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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. Exclusion Criteria 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ben Palanca, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to share IPD.

Learn more about this trial

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

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