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

Depressive Disorder, Major Clinical Trial

— NARSAD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03283670
• Other study ID #: 201608024
• Status: Completed
• Phase: Phase 2
• Start date: November 22, 2016
• Est. completion date: February 18, 2020

Study information

• Verified date: March 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 18, 2020
• Est. primary completion date: February 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Disease

Intervention

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.
• 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.
• Placebo Gas
Placebo gas given at 50% nitrogen [inert]/50% oxygen.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Brain & Behavior Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 and 24 hours after inhalation