Nitrous TRD Bipolar Depression

Nitrous Oxide - A Novel Therapy for Treatment-Resistant Bipolar Depression

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.

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder; Treatment- Resistant Bipolar Disorder; Bipolar Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Nitrous Oxide

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)	Drug: Placebo; 50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)
Experimental: Nitrous Oxide; 50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)	Drug: Nitrous Oxide; 50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F); Other Names: Laughing Gas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MADRS (Montgomery Asberg Depression Rating Scale)	Change in depressive symptoms on MADRS scale between baseline and day 7 follow up	up to 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale-17 Item (Ham-D17)		up to1week
Young Mania Rating Scale (YMRS) to Assess Emergence of Mania/Hypomania	Young Mania Rating Scale (YMRS) to assess emergence of mania/hypomania (patients with YMRS scores > 12 will be removed from the trial and recommended for follow up treatment per Psychiatry P.I., i.e., nitrous oxide treatments discontinued)	up to 1 week

Other Outcome Measures

Outcome Measure	Time Frame
Profile of Mood States (POMS) Short Form to Assess for Rapid/Instantaneous Changes in Mood/Affect	up to 1 week
Quick Inventory of Depressive Symptomatology- Self Report (QIDS -SR) Patient-rated Depression Measure	up to 1 week
Clinician Administered Dissociative States Scale (CADSS) for Emergence of Disassociation	up to 1week
Brief Psychiatric Rating Scale (BPRS) to Assess Psychotic or Hallucinogenic Behavior	up to 1 week
Scale for Suicidal Ideation (SSI) to Assesses for Emergence of Suicidal Thinking	up to 1 week

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: PPD; Stanley Medical Research Institute
• Investigators: Principal Investigator: Ben Palanca, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2016
• Primary Completion (Actual): December 6, 2016
• Study Completion (Actual): December 6, 2016

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 27, 2016
• First Posted (Estimate): May 2, 2016

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Nitrous Oxide; Bipolar Depressive Disorder; Treatment- Resistant Bipolar Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Disease; Bipolar Disorder; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Nitrous Oxide
• Other Study ID Numbers: 201509128