Nitrous Oxide for Major Depressive Disorder

NCT03932825 | Completed Phase 2

• 1 other identifier: 18-05-04-XY-0001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims at investigating the persistence of antidepressant effect of Nitrous Oxide (N2O) for Treatment-Resistant Depression(TRD). The investigators also aim to assess the effect of N2O on the electroencephalograph, multimodal magnetic resonance imaging(MRI), blood cytokines, feces bacteria flora and neuropsychological performance in patients with TRD. The investigators further aim to identify the predictors of N2O's antidepressant effeect using the above techniques.

Conditions

Depressive Disorder; Major Depressive Disorder; Treatment Resistant Depression; Depressive Disorder, Major; Depression

Keywords

Nitrous Oxide; Laughing Gas

Outcome Measures

Primary Outcomes (3)

• Change in Hamilton Depression Rating Scale-17 item (HDRS-17)

  Interview-based questionnaire used to measure the severity of depression. Consists of 17 items with a score calculated. Higher scores are associated with more severe depression. 0 - 7 = Normal; 8 - 17 = Mild Depression; 18 - 24 = Moderate Depression; \> 25 = Severe Depression; Maximum score = 52

  Baseline, 2hours, 24hours, 7days, 2weeks

• Change in QIDS-16-SR (Quick Inventory of Depressive Symptomatology-16 Self Report)

  This is a 16-item self report questionnaire that measures depressive symptoms. Improvement is reported in change in depressive score score ranges from 0-27, with higher numbers indicating more severe symptom reporting. Change is calculated by baseline plus/minus the value at the later time point

  Baseline, 2hours, 24hours, 7days, 2weeks

• Change in Visual Analog Scale-Depression (VAS-D)

  All patients are asked to fill out visual analog scale for depression (VAS-D) before and after the intervention. VAS-D is a self-report scale for ddepression severity, with 0 score indicating not at all depressed and 10 score indicating extremely depressed.

  Baseline, 2hours, 24hours, 7days, 2weeks

Secondary Outcomes (11)

• Chang in Event Related Potentials (ERPs)

  Baseline, 24hours, 7days, 2weeks

• Change in voxel-based morphometry of grey matter, white matter as assessed by structural magnetic resonancce imaging.

  Baseline, 24hours

• Change in Functional connectivity

  Baseline, 24hours

• Change in peripheral blood cytokines

  Baseline, 2hours, 24hours

• Change in feces bacterial flora

  Baseline

Other Outcomes (4)

• Change in Heart Rate Variability

  Baseline, 2hours, 24hours, 7days, 2weeks

• Number of Participants With Adverse Events AEs

  Baseline, 2hours, 24hours, 7days, 2weeks

• Clinician-Administered Dissociative States Scale (CADSS) Scores During inhaled nitrous oxide

  Baseline, 2hours, 24hours

Study Arms (2)

Air oxygen mixture

PLACEBO COMPARATOR

participants in this arm inhale mixed oxygen-air gas (inspired oxygen concentration \~50%).

Drug: Placebo

Nitrous oxide

EXPERIMENTAL

Participants in this group inhale mixed 50% nitrous oxide and 50% oxygen.

Drug: Nitrous Oxide

Interventions

Nitrous Oxide DRUG

An 1-hour session of inhaled nitrous oxide at concentrations of 50%.

Also known as: Laughing Gas, Xiao Qi, 笑气

Nitrous oxide

Placebo DRUG

An 1-hour session of mixed oxygen-air gas(inspired oxygen concentration \~50%)

Also known as: Air oxygen mixture

Air oxygen mixture

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult (≥18 years, both sexes), with ICD-10 criteria for MDD without psychosis, as determined by a structured clinical interview Mini International Neuropsychiatric Interview
• Moderate to severe depression, as defined by a pretreatment score \>17 on the HDRS-17 scale
• TRD was defined as having had at least two adequate dose-duration, antidepressant medication failures in the current episode and a lifetime failure of at least three antidepressant medication trials.
• Informed consent to participate in this study

You may not qualify if:

• 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
• Active or recent (\<12 months) substance abuse or dependence; excluding nicotine
• Presence of acute medical illness that could interfere with study participation, including significant pulmonary disease
• Acute severe suicidal ideation
• Acute psychosis
• Received ECT treatment within 6 months
• History of NMDA-antagonists (e.g., ketamine) intake
• Pregnancy or breastfeeding
• 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).

Sponsors & Collaborators

• Lingjiang Li: lead

Study Sites (1)

Mental Health Institute & Faculty of Psychiatry of The Second Xiangya Hospital, Central South University

Changsha, Hunan, 410001, China

Location

MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Depression

Interventions

Nitrous Oxide; xiao-cheng-qi-tang

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds

Study Officials

• Lingjiang Li, MD

  Mental Health Institute, the Second Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: President of Chinese Psychiatry Society of Chinese Medical Association

Study Record Dates

• First Submitted: April 20, 2019
• First Posted: May 1, 2019
• Study Start: April 1, 2019
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: April 8, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)