Clinical trial NCT03932825: Nitrous Oxide for Major Depressive Disorder
Official title: A Clinical Trial of Nitrous Oxide for Treatment-Resistant Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder
Major Depressive Disorder
Treatment Resistant Depression
Depressive Disorder, Major
Depression
Keywords: Nitrous Oxide
Laughing Gas
Lead sponsor: Central South University
Sponsor class: OTHER
First posted: 2019-05-01
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Change in Hamilton Depression Rating Scale-17 item (HDRS-17)
timeFrame: Baseline, 2hours, 24hours, 7days, 2weeks
measure: Change in QIDS-16-SR (Quick Inventory of Depressive Symptomatology-16 Self Report)
timeFrame: Baseline, 2hours, 24hours, 7days, 2weeks
measure: Change in Visual Analog Scale-Depression (VAS-D)
timeFrame: Baseline, 2hours, 24hours, 7days, 2weeks
Secondary outcomes:
measure: Chang in Event Related Potentials (ERPs)
timeFrame: Baseline, 24hours, 7days, 2weeks
measure: Change in voxel-based morphometry of grey matter, white matter as assessed by structural magnetic resonancce imaging.
timeFrame: Baseline, 24hours
measure: Change in Functional connectivity
timeFrame: Baseline, 24hours
measure: Change in peripheral blood cytokines
timeFrame: Baseline, 2hours, 24hours
measure: Change in feces bacterial flora
timeFrame: Baseline
measure: Change in the TMT/A and B (Executive Function)
timeFrame: Baseline, 24hours, 7days, 2weeks
measure: Change in Congruent STROOP Time to Complete (Executive Function)
timeFrame: Baseline, 24hours, 7days, 2weeks
measure: Digit-Span Test
timeFrame: Baseline, 24hours, 7days, 2weeks
measure: Change in DSST (Number of Correct Symbols)
timeFrame: Baseline, 24hours, 7days, 2weeks
measure: Improvement on Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: Baseline, 2hours, 24hours, 7days, 2weeks
measure: Change in Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: Baseline, 2hours, 24hours, 7days, 2weeks
Other outcomes:
measure: Change in Heart Rate Variability
timeFrame: Baseline, 2hours, 24hours, 7days, 2weeks
measure: Number of Participants With Adverse Events AEs
timeFrame: Baseline, 2hours, 24hours, 7days, 2weeks
measure: Clinician-Administered Dissociative States Scale (CADSS) Scores During inhaled nitrous oxide
timeFrame: Baseline, 2hours, 24hours
measure: Suicidal ideation as assessed by the Scale for Suicide Ideation (SSI)
timeFrame: Baseline, 2hours, 24hours, 7days, 2weeks
Locations:
city: Changsha
country: China
facility: Mental Health Institute & Faculty of Psychiatry of The Second Xiangya Hospital, Central South University
state: Hunan
Study officials:
affiliation: Mental Health Institute, the Second Xiangya Hospital of Central South University
name: Lingjiang Li, MD
role: PRINCIPAL_INVESTIGATOR
References: