Overview

This trial is active, not recruiting.

Conditions depression, major depressive disorder
Treatments nitrous oxide, placebo
Phase phase 2
Sponsor Washington University School of Medicine
Start date November 2012
End date December 2016
Trial size 40 participants
Trial identifier NCT02139540, 201204023

Summary

Major depressive disorder (MDD) is a global medical problem with significant shortcomings in current therapy. Chief among these is the delay between initiation of pharmacologic therapy and clinical improvement in symptoms. Recently ketamine, an NDMA-receptor antagonist has been shown to rapidly and effectively reverse the symptoms of MDD. Nitrous oxide, another NMDA-receptor antagonist, may produce the same effect with a cleaner side-effect profile and perhaps without the need for intravenous access and anesthesia personnel. Therefore, we propose conducting a pilot randomized placebo controlled double-blind crossover study in which patients will receive up to 50% nitrous oxide in oxygen or up to 50% oxygen in air for a period of one hour in addition to standard medical therapy. Depression severity will be assessed by a blinded observer pre-treatment, 30 minutes and 2 hours post treatment using the Hamilton depression rating scale.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Other)
First session: Nitrous oxide Second session: placebo
nitrous oxide Laughing Gas
Patients will receive either up to 50% nitrous oxide/50% oxygen for 1 hour or "placebo" (50% nitrogen [inert]/50% oxygen) in two separate sessions. Both sessions will be 1 week apart.
placebo 50% nitrogen [inert]/50% oxygen
50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup
(Other)
First session: Placebo Second session: Nitrous Oxide
nitrous oxide Laughing Gas
Patients will receive either up to 50% nitrous oxide/50% oxygen for 1 hour or "placebo" (50% nitrogen [inert]/50% oxygen) in two separate sessions. Both sessions will be 1 week apart.
placebo 50% nitrogen [inert]/50% oxygen
50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup

Primary Outcomes

Measure
Change in HDRS-21 (21-point Hamilton Depression Rating Scale)
time frame: baseline and 24 hours

Secondary Outcomes

Measure
Change in QIDS -SR [Quick Inventory of Depressive Symptomatology - Self Report]
time frame: baseline and 24 hours
Clinical Depression Endpoints
time frame: 24 hours
Change in Plasma Total Homocysteine
time frame: baseline and 24hours

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria

  • Adults 18-65 years of age
  • Major depressive disorder without psychosis with as determined by structured interview using the Mini-International Neuropsychiatric Interview (MINI). (baseline )
  • HDRS-21 score of >18
  • Good command of the English language

Exclusion Criteria

  • Bipolar disorder
  • Schizoprenia
  • Schizoaffective disorder
  • Obsessive-compulsive disorder, panic disorder
  • Substance abuse or dependence (except for remote substance abuse or dependence with remission at least 1 year prior to the study and except for nicotine use disorders)
  • Axis II diagnoses that may interfere with the patient's ability to improve on nitrous oxide
  • Acute medical illness that may pose subject at risk during nitrous oxide administration
  • Active suicidal intention (inability to contract for safety)
  • Active psychotic symptoms
  • Patients with significant pulmonary disease and/or requiring supplemental oxygen
  • 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
  • Previous administration of NMDA-receptor antagonists (e.g., ketamine) within the last 3 months
  • Current electro-convulsive therapy treatment
  • Any active suicidal ideation, intention, or planning (clinical assessment of suicidality will be used)

Additional Information

Official title Nitrous Oxide as Treatment for Major Depression - a Pilot Study
Principal investigator Peter Nagele, MD, MSc
Description We will study 20 patients with non-treatment resistant major depression and 20 patients with treatment-resistant major depression, defined as failure of at least 2 antidepressants in the current depressive episode and 3 lifetime medication failures.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Washington University School of Medicine.