Nitrous Oxide for the Treatment of Major Depressive Disorder

NCT ID: NCT03869736

Last Updated: 2024-12-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-22
• Study Completion Date: 2023-12-10

Brief Summary

The investigators are conducting a randomized controlled trial to evaluate the antidepressant effects of nitrous oxide in people with Major Depressive Disorder (MDD). MDD is a global medical condition that causes significant health and economic burden. Recent studies have shown that a single dose of ketamine, an NMDA-antagonist, has fast and long lasting anti-depressant effect. Nitrous oxide, another NMDA-antagonist, is widely used for anesthesia and analgesia, safer to administer and has fewer side effects than ketamine.

A randomized controlled crossover feasibility study showed significant reduction in depressive symptoms at 2 and 24 hours after a single 1-hour treatment session of inhaled nitrous oxide compared with placebo. Nitrous oxide is inexpensive and can be safely administered by any trained clinician. If found to be efficacious, it could be used to provide rapid anti-depressant effect whilst the benefit of traditional anti-depressants has its delayed effect. Another potential application could be in acutely suicidal patients.

This investigated-initiated phase 2b trial will enable confirmation and extension of the findings from the feasibility study, and identify the optimal dose and regimen in a broader population of those with MDD. Participants will be randomized to receive a weekly 1-hour inhalational sessions of either nitrous oxide or placebo (oxygen-air mixture) for 4 weeks, and the nitrous group will be further randomly assigned to a dose of 50% nitrous oxide or 25% nitrous oxide. Depression severity will be assessed by a blinded observer pre-treatment and at weekly intervals during and for 4 weeks after treatment using the Hamilton Depression Rating Scale.

Conditions

Depression; Major Depressive Disorder

Keywords

Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Nitrous Oxide; Anesthetics, Inhalational; Anesthetics; Anesthetics, General; Physiologic Effects of Drugs; Analgesics, Non-Narcotic; Analgesics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nitrous Oxide 50% or 25%

Nitrous oxide at an inhaled concentration of 50% or 25%

Group Type: EXPERIMENTAL

Nitrous Oxide

Intervention Type: DRUG

1-hour sessions of inhaled nitrous oxide at concentrations of 25% or 50% (randomly assigned) to be administered weekly for 4 weeks.

Placebo

Oxygen-air mixture

Group Type: SHAM_COMPARATOR

Placebo

Intervention Type: DRUG

1-hour sessions of inhaled oxygen-air mixture (inspired oxygen concentration \~23-30%) to be administered weekly for 4 weeks.

Interventions

Nitrous Oxide

1-hour sessions of inhaled nitrous oxide at concentrations of 25% or 50% (randomly assigned) to be administered weekly for 4 weeks.

Intervention Type: DRUG

Placebo

1-hour sessions of inhaled oxygen-air mixture (inspired oxygen concentration \~23-30%) to be administered weekly for 4 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult (≥18 years, both sexes), with DSM-IV-TR criteria for MDD without psychosis, as determined using a structured clinical interview [Mini International Neuropsychiatric Interview]

2. MDD, as defined by a pretreatment score >18 on the HDRS-21 scale

Exclusion Criteria

1. A history of bipolar disorder, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses; active suicidal intention, as determined by clinical interview

2. Active or recent (<12 months) substance abuse or dependence; excluding nicotine

3. Administration of NMDA-antagonists (e.g., ketamine) in previous 3 months

4. Ongoing treatment with ECT

5. Presence of acute medical illness that could interfere with study participation, including significant pulmonary disease

6. Pregnancy or breastfeeding

7. Any contraindications to the use of nitrous oxide (e.g., pneumothorax, middle ear occlusion, elevated intracranial pressure, chronic cobalamin or folate deficiency unless treated with folic acid or vitamin B12).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayside Health

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Myles, MD

Role: PRINCIPAL_INVESTIGATOR

The Alfred

Locations

University of Chicago Medicine

Chicago, Illinois, United States

Alfred Hospital

Melbourne, Victoria, Australia

Countries

United States; Australia

Other Identifiers

438/19

Identifier Type: -

Identifier Source: org_study_id