Nitrous Oxide as Treatment for Major Depression - a Pilot Study

• ClinicalTrials.gov Identifier: NCT02139540
• Recruitment Status: Completed
• First Posted: May 15, 2014
• Results First Posted: January 27, 2020
• Last Update Posted: January 27, 2020
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

Tracking Information

• First Submitted Date: May 13, 2014
• First Posted Date: May 15, 2014
• Results First Submitted Date: April 23, 2018
• Results First Posted Date: January 27, 2020
• Last Update Posted Date: January 27, 2020
• Actual Study Start Date: November 2012
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2020)

Change in Hamilton Depression Rating Scale HDRS-21 [ Time Frame: baseline and 24 hours ]

(21-point Hamilton Depression Rating Scale) Scoring is based on the first 17 items on the 21 point scale. Eight items are scored on a 5-point scale, ranging form 0=not present to 4= severe. Nine are scored from 0-2.

• Original Primary Outcome Measures (submitted: May 14, 2014): Change in HDRS-21 (21-point Hamilton Depression Rating Scale) [ Time Frame: baseline and 24 hours ]

Current Secondary Outcome Measures (submitted: January 23, 2020)

Change in Quick Inventory of Depressive Symptomatology - Self Report - QIDS -SR [ Time Frame: baseline and 24 hours ]

[Quick Inventory of Depressive Symptomatology - Self Report] An item-by-item severity scale of 0 to 3, with possible total scores ranging from 0 to 84. The items on the scale are added together for a total score. Higher scores mean worse outcome.

Original Secondary Outcome Measures (submitted: May 14, 2014)

• Change in QIDS -SR [Quick Inventory of Depressive Symptomatology - Self Report] [ Time Frame: baseline and 24 hours ]
• Clinical Depression Endpoints [ Time Frame: 24 hours ]
  Rates of response (HRDS<50% compared to baseline) and remission (HRDS ≤ 7 points) according to the HRDS-21
• Change in Plasma Total Homocysteine [ Time Frame: baseline and 24hours ]

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: May 14, 2014)

Number of Adverse Events [ Time Frame: 24 hours ]

• Cardiovascular AEs, such as hyper- and hypotension, tachy-/bradycardia
• Respiratory AEs, such as respiratory depression and desaturation
• Psychiatric AEs, such as psychotic symptoms or suicidal ideation

Descriptive Information

• Brief Title: Nitrous Oxide as Treatment for Major Depression - a Pilot Study
• Official Title: Nitrous Oxide as Treatment for Major Depression - a Pilot Study
• Brief 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Depression
• Major Depressive Disorder

Intervention

• Drug: Nitrous Oxide
  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.
  Other Name: Laughing Gas
• Drug: Placebo
  50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup
  Other Name: 50% nitrogen [inert]/50% oxygen

Study Arms

• N2O/Placebo
  First session: Nitrous oxide Second session: placebo
  Interventions:

  • Drug: Nitrous Oxide
  • Drug: Placebo
• Placebo/N2O
  First session: Placebo Second session: Nitrous Oxide
  Interventions:

  • Drug: Nitrous Oxide
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 23, 2020): 21
• Original Estimated Enrollment (submitted: May 14, 2014): 40
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adults 18-65 years of age

2. Major depressive disorder without psychosis with as determined by structured interview using the Mini-International Neuropsychiatric Interview (MINI).

   (baseline )

3. HDRS-21 score of >18
4. Good command of the English language

Exclusion Criteria:

History of:

1. Bipolar disorder
2. Schizoprenia
3. Schizoaffective disorder
4. Obsessive-compulsive disorder, panic disorder
5. 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)
6. Axis II diagnoses that may interfere with the patient's ability to improve on nitrous oxide
7. Acute medical illness that may pose subject at risk during nitrous oxide administration
8. Active suicidal intention (inability to contract for safety)
9. Active psychotic symptoms
10. Patients with significant pulmonary disease and/or requiring supplemental oxygen

11. 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
12. Previous administration of NMDA-receptor antagonists (e.g., ketamine) within the last 3 months
13. Current electro-convulsive therapy treatment
14. Any active suicidal ideation, intention, or planning (clinical assessment of suicidality will be used)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02139540
• Other Study ID Numbers: 201204023
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Washington University School of Medicine
• Original Responsible Party: Same as current
• Current Study Sponsor: Washington University School of Medicine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Peter Nagele, MD, MSc; Washington University School of Medicine

• PRS Account: Washington University School of Medicine
• Verification Date: January 2020