Nitrous Oxide as a Putative Novel Dual-Mechanism Treatment for Bipolar Disorder

Bipolar Disorder Clinical Trial

Official title:

Nitrous Oxide as a Putative Novel Dual-Mechanism Treatment for Bipolar Disorder

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02351869
• Other study ID #: 435-2013
• Status: Terminated
• Phase: Phase 2
• Start date: August 2015
• Est. completion date: June 7, 2020

Study information

• Verified date: April 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a 7-day randomized, double-blind proof-of-concept pilot study of nitrous oxide vs. midazolam in 40 adults (20-60 years) with bipolar disorder (BD) (type I or II). Ongoing pharmacological and psychosocial treatments may continue, provided that they have not been initiated or significantly modified in the preceding 2 weeks. Participants' current treatment as prescribed by clinical psychiatrists will not be modified or interfered in this study. The study involves 3 visits. During study visit 1, participants will complete screening to ensure study eligibility. This will be done using interview measures. During study visit 2, participants will complete anthropomorphic measurements, measurement of endothelial function, screening blood work, ECGs, and an anaesthesia screener. During study visit 3, participants will receive the treatment (nitrous oxide or midazolam), complete an MRI scan, and complete interview measures and self-reports. There will be anthropomorphic measurements taken as well. The participant will be required to complete phone interviews and self-reports over the subsequent 7 days. There are 4 main predictions: 1. Nitrous oxide will significantly reduce depression symptoms vs. midazolam. 2. Nitrous oxide will significantly increase frontal cortical perfusion vs. midazolam. 3. Lower perfusion in frontal cortical regions at baseline will be associated with greater improvement in depression symptoms following nitrous oxide treatment. 4. Poorer endothelial function will be associated with greater improvement in depression symptoms following nitrous oxide treatment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: June 7, 2020
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 60 Years

Eligibility

Inclusion Criteria:

English-speaking; age 20-60 years; BD-I or BD-II, current major depressive episode =4 weeks duration; MADRS=22; taking =1 mood stabilizing medication/s (i.e. antimanic anticonvulsant, antipsychotic, and/or lithium). Exclusion Criteria: New medications or changes in dosing, or ECT or TMS, in the preceding 2 weeks; MADRS item 10, > 4; YMRS=12; acute significant suicidality; psychosis; substance abuse (past 3 months); active major medical conditions (hepatic, renal, respiratory, or cardio/cerebrovascular disease; diabetes; esophageal reflux; sleep apnea); B12 deficiency/disorders; pregnant; MRI contraindications; history of adverse anaesthetic reactions; anaesthesia class >2; scuba diving in preceding week.

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Nitrous Oxide

• Midazolam

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

References & Publications (2)

Dimick MK, Omrin D, MacIntosh BJ, Mitchell RHB, Riegert D, Levitt A, Schaffer A, Belo S, Iazzetta J, Detzler G, Choi M, Choi S, Orser BA, Goldstein BI. Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept stu — View Citation

Kim WSH, Dimick MK, Omrin D, Mitchell RHB, Riegert D, Levitt A, Schaffer A, Belo S, Iazzetta J, Detzler G, Choi M, Choi S, Herrmann N, McIntyre RS, MacIntosh BJ, Orser BA, Goldstein BI. Proof-of-concept randomized controlled trial of single-session nitrou — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Montgomery-Asberg Depression Scale (MADRS) score	Measures mood symptom severity, used to select patients and assess treatment efficacy. Although other time-points will be examined, 24h was selected as the primary outcome to minimize the impact of acute sedation and psychoactive effects.	Assessed at baseline, an average of 3 days later, again at up to 5 days after baseline on the day of drug administration, and participants will be followed for 7 days after the drug administration
Secondary	Young Mania Rating Scale (YMRS)	Measures symptom severity	Assessed at baseline, an average of 3 days later, again at up to 5 days after baseline on the day of drug administration, and participants will be followed for 7 days after the drug administration
Secondary	Blood Pressure		Measured an average of 3 days post-baseline and again approximately every hour on the drug administration day
Secondary	Weight		Assessed an average of 3 days after baseline
Secondary	Beck Depression Inventory (BDI-II)	Self-report measure of mood severity	Assessed on the drug administration day and followed for 7 days post-drug administration
Secondary	Heart Rate		Measured an average of 3 days post-baseline and again approximately every hour on the drug administration day
Secondary	Brief Psychiatric Rating Scale		Assessed on the drug administration day and followed for 7 days post-drug administration
Secondary	The Clinician Administered Dissociative States Scale (CADSS)		Assessed on the drug administration day and followed for 7 days post-drug administration
Secondary	General Information Sheet (Demographics)	Demographics	Collected at baseline
Secondary	Hamilton Anxiety Rating Scale (HAM-A)	Interview measure used to assess anxiety severity	Assessed on the drug administration day and followed for 7 days post-drug administration
Secondary	Hamilton Depression Rating Scale (HDRS)	Interview measure used to assess mood severity	Assessed on the drug administration day and followed for 7 days post-drug administration
Secondary	Patient Rated Inventory of Side Effects	Self-report used to assess side effects	Assessed on the drug administration day and followed for 7 days post-drug administration
Secondary	CANTAB Medication Listing	Used to collect medications taken the day before and on the day of blood work	Assessed an average of 3 days after baseline
Secondary	Structured Clinical Interview for DSM Disorders	Interview measure used to assess DSM disorders	Assessed at baseline
Secondary	Visual Analogue Scale		Assessed on the drug administration day and followed for 7 days post-drug administration
Secondary	Height		Assessed an average of 3 days after baseline
Secondary	Endothelial Function assessed via RH-PAT using the EndoPAT.	Will be assessed via RH-PAT using the EndoPAT.	Assessed an average of 3 days after baseline and lasts approximately 30 minutes
Secondary	Frontal Perfusion assessed using an MRI scan	Will be assessed using an MRI scan.	Assessed approximately 5 days after baseline and post-drug administration
Secondary	Biomarkers (B12 and nitric oxide (NO))	B12 and nitric oxide (NO) will be examined as predictors of response owing to known associations with the mechanism of action of N2O.	Assessed an average of 3 days after baseline