Clinical trial NCT02757521: Nitrous TRD Bipolar Depression
Official title: Nitrous Oxide - A Novel Therapy for Treatment-Resistant Bipolar Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Treatment- Resistant Bipolar Disorder
Bipolar Disorder
Bipolar Depressive Disorder
Keywords: Bipolar Depressive Disorder
Treatment- Resistant Bipolar Disorder
Nitrous Oxide
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
name: PPD Development, LP
First posted: 2016-05-02
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigators will study approximately 64 patients with Treatment-Resistant Bipolar Depressive Disorder, defined as a failure of at least 1 antidepressants in the current depressive episode and 2 lifetime medication failures. The study will last approximately 6 to 8 weeks, involving randomization into one of two treatment groups receiving 3 one hour long inhalation treatments over a week.

Detailed description: Investigators will study approximately 64 patients with Treatment-Resistant Bipolar Depressive Disorder, defined as a failure of at least 1 antidepressants in the current depressive episode and 2 lifetime medication failures. The study will last approximately 6 to 8 weeks, involving randomization into one of two treatment groups receiving 3 one hour long inhalation treatments over a week. Post-treatment assessments follow each inhalation treatment and are conducted 1 week and 2 weeks following the final inhalation treatment. Patients are then randomized again into the Second Stage of the study, involving the same treatment and post-treatment schedule as the First Stage detailed above.

Eligibility criteria: Inclusion Criteria:

* Adults 18-65 years of age
* Treatment-resistant bipolar depressive disorder without psychosis and a MADRS baseline score of \>20. All patients must have history of being on a serum-verified (at time of entry into study) mood stabilizer \[lithium at 0.5-1.2mEq/L; or valproic acid, 50-125mcg/ml\] for 4 weeks prior to entry into the study and remain on this mood stabilizer during the course of the trial. Further, subjects will have failed two adequate dose/duration antidepressant courses in their lifetime, including one in the current depressive episode (verified by Antidepressant Treatment History Form).
* Good command of the English language

Exclusion Criteria:

* Schizophrenia
* Schizoaffective disorder
* Obsessive-compulsive disorder or panic disorder
* Active or recent substance abuse or dependence (in remission at least 1 year prior to the study; exception = nicotine use disorders)
* A diagnosis of personality disorder that may interfere with the patient's ability to improve on nitrous oxide as determined by study investigator
* Acute medical illness that may pose subject at risk during nitrous oxide administration (neurological disorders or medical disorders including dementia, stroke, encephalopathy, Parkinson's Disease, brain tumors, multiple sclerosis, seizure disorder, severe cardiac disease, any disease known to affect drug metabolism and excretion, i.e. renal or liver disease) per P.I. discretion
* 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); current electro-convulsive therapy treatment

Primary outcomes:
measure: Change in MADRS (Montgomery Asberg Depression Rating Scale)
timeFrame: up to 1 week
Secondary outcomes:
measure: Hamilton Depression Rating Scale-17 Item (Ham-D17)
timeFrame: up to1week
measure: Young Mania Rating Scale (YMRS) to Assess Emergence of Mania/Hypomania
timeFrame: up to 1 week
Other outcomes:
measure: Profile of Mood States (POMS) Short Form to Assess for Rapid/Instantaneous Changes in Mood/Affect
timeFrame: up to 1 week
measure: Quick Inventory of Depressive Symptomatology- Self Report (QIDS -SR) Patient-rated Depression Measure
timeFrame: up to 1 week
measure: Clinician Administered Dissociative States Scale (CADSS) for Emergence of Disassociation
timeFrame: up to 1week
measure: Brief Psychiatric Rating Scale (BPRS) to Assess Psychotic or Hallucinogenic Behavior
timeFrame: up to 1 week
measure: Scale for Suicidal Ideation (SSI) to Assesses for Emergence of Suicidal Thinking
timeFrame: up to 1 week
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Ben Palanca, MD
role: PRINCIPAL_INVESTIGATOR
References: