Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies (NARSAD)

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ClinicalTrials.gov Identifier: NCT03283670

Recruitment Status : Completed

First Posted : September 14, 2017

Results First Posted : April 4, 2022

Last Update Posted : April 4, 2022

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Sponsor:

Collaborator:

Brain & Behavior Research Foundation

Information provided by (Responsible Party):

Ben Palanca, Washington University School of Medicine

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
Conditions	Depressive Disorder, Major Depressive Disorder, Treatment-Resistant
Interventions	Drug: Nitrous Oxide 25% Drug: Nitrous Oxide 50% Drug: Placebo Gas
Enrollment	24

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Study Participants
Arm/Group Description	Participants will be studied for 14...
Arm/Group Description	Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned. 25% nitrous oxide, 25% nitrogen, 25% oxygen 50% nitrous oxide, 50% oxygen Placebo gas: 50% nitrogen(inert), 50% oxygen
Period Title: Placebo Gas
Started	24
Completed	22
Not Completed	2
Reason Not Completed
Withdrawal by Subject	2
Period Title: 25% Nitrous Oxide
Started	24
Completed	20
Not Completed	4
Reason Not Completed
Withdrawal by Subject	4
Period Title: 50% Nitrous Oxide
Started	24
Completed	23
Not Completed	1
Reason Not Completed
Withdrawal by Subject	1

Baseline Characteristics

Arm/Group Title		Study Participants
Arm/Group Description		Participants will be studied for 14...
Arm/Group Description		Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned. 25% nitrous oxide, 25% nitrogen, 25% oxygen 50% nitrous oxide, 50% oxygen Placebo gas: 50% nitrogen(inert), 50% oxygen
Overall Number of Baseline Participants		24
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	20 83.3%
	>=65 years	4 16.7%
Age, Continuous Mean (Full Range) Unit of measure: Years
	Number Analyzed	24 participants
		44 (26 to 68)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants
	Female	17 70.8%
	Male	7 29.2%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	1 4.2%
	White	23 95.8%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	24 participants
United States		24

Outcome Measures

1.Primary Outcome


Title	Change in Depression Symptoms Measured by the Hamilton Depression Rating Scale- 21 Items
Description	Change in depression symptoms measured by the Hamilton Depression Rati...
Description	Change in depression symptoms measured by the Hamilton Depression Rating Scale- 21 items. The HAMD-21 is designed to rate the severity of depression in patients. Although it contains 21 areas, calculate the patient's score as the total score on the first 17 answers. Scale: 0=absent, 4=worst level possible) the scores on the individual items are summed. Changes will be based on measurements obtained at baseline, approximately 2 hours after inhalation, and approximately 24 hours after inhalation. Changes are based on subtracti on of baseline score.
Time Frame	2 and 24 hours after inhalation

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	25% Nitrous Oxide	50% Nitrous Oxide	Placebo Gas
Arm/Group Description:	25% nitrous oxide, 25% nitrogen, 25...	50% nitrous oxide, 50% oxygen. Part...	50% nitrogen(inert), 50% oxygen. Pa...
Arm/Group Description:	25% nitrous oxide, 25% nitrogen, 25% oxygen. Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.	50% nitrous oxide, 50% oxygen. Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.	50% nitrogen(inert), 50% oxygen. Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.
Overall Number of Participants Analyzed	20	23	22
Mean (Standard Deviation) Unit of Measure: score on a scale
2 Hours	-3.0 (3.9)	-3.8 (4.30)	-3.9 (4.3)
24 Hours	-4.0 (6.6)	-5.5 (5.8)	-6.0 (6.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	25% Nitrous Oxide, Placebo Gas
	Comments	HAMD-21 at 2 Hours, placebo vs 25% nitrous oxide
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.55
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.75
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	25% Nitrous Oxide, Placebo Gas
	Comments	Change in HAMD-21, 25% nitrous oxide vs placebo at 24 hours
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.47
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.4
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	50% Nitrous Oxide, Placebo Gas
	Comments	HAMD-21 at 2 Hours, placebo vs 50% nitrous oxide
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.49
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-0.87
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	50% Nitrous Oxide, Placebo Gas
	Comments	Change in HAMD-21 at 24 hours, placebo vs 50% nitrous oxide
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.34
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.9
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	25% Nitrous Oxide, 50% Nitrous Oxide
	Comments	Change in HAMD-21 at 2 hours, 25% nitrous oxide vs 50% nitrous oxide
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.94
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.11
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	25% Nitrous Oxide, 50% Nitrous Oxide
	Comments	Change in HAMD-21 at 24 hours, 25% nitrous oxide vs 50% nitrous oxide
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.80
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	18 weeks
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Placebo		25% Nitrous Oxide		50% Nitrous Oxide
Arm/Group Description	Placebo gas: 50% nitrogen(inert), 5...		25% nitrous oxide, 25% nitrogen, 25...		50% nitrous oxide, 50% oxygen
Arm/Group Description	Placebo gas: 50% nitrogen(inert), 50% oxygen		25% nitrous oxide, 25% nitrogen, 25% oxygen		50% nitrous oxide, 50% oxygen
All-Cause Mortality
	Placebo		25% Nitrous Oxide		50% Nitrous Oxide
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/22 (0.00%)		0/20 (0.00%)		0/23 (0.00%)
Serious Adverse Events Serious Adverse Events
	Placebo		25% Nitrous Oxide		50% Nitrous Oxide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0.00%)		0/20 (0.00%)		0/23 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo		25% Nitrous Oxide		50% Nitrous Oxide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/22 (22.73%)		8/20 (40.00%)		14/23 (60.87%)
Gastrointestinal disorders
Nausea ^†	0/22 (0.00%)	0	1/20 (5.00%)	1	5/23 (21.74%)	5
Vomiting ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	2/23 (8.70%)	2
Intestinal gas ^†	0/22 (0.00%)	0	1/20 (5.00%)	1	0/23 (0.00%)	0
Stomach virus ^†	2/22 (9.09%)	2	0/20 (0.00%)	0	0/23 (0.00%)	0
General disorders
Car crash (minor) ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	1/23 (4.35%)	1
Infections and infestations
Common cold/strep throat ^†	0/22 (0.00%)	0	2/20 (10.00%)	2	3/23 (13.04%)	3
Musculoskeletal and connective tissue disorders
Cramps ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	1/23 (4.35%)	1
Nervous system disorders
Haziness ^†	0/22 (0.00%)	0	1/20 (5.00%)	1	3/23 (13.04%)	3
Dizziness ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	3/23 (13.04%)	3
Lightheadedness ^†	0/22 (0.00%)	0	1/20 (5.00%)	1	2/23 (8.70%)	2
Feeling high ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	3/23 (13.04%)	3
Headache ^†	3/22 (13.64%)	3	2/20 (10.00%)	2	4/23 (17.39%)	4
Sleepiness ^†	0/22 (0.00%)	0	1/20 (5.00%)	1	2/23 (8.70%)	2
Weakness/heave ^†	0/22 (0.00%)	0	1/20 (5.00%)	1	2/23 (8.70%)	2
Dry Mouth ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	2/23 (8.70%)	2
Tingling ^†	0/22 (0.00%)	0	1/20 (5.00%)	1	3/23 (13.04%)	3
Fainting spell ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	1/23 (4.35%)	1
Psychiatric disorders
Laughing ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	3/23 (13.04%)	3
Feeling disconnected ^†	1/22 (4.55%)	1	0/20 (0.00%)	0	6/23 (26.09%)	6
Memory gaps ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	1/23 (4.35%)	1
Paranoia ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	1/23 (4.35%)	1
Surgical and medical procedures
Sore throat ^†	0/22 (0.00%)	0	0/20 (0.00%)	0	1/23 (4.35%)	1
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Ben Palanca, MD PhD
Organization:	Washington University
Phone:	314 273-9076
EMail:	palancab@wustl.edu

Layout table for additonal information

Responsible Party:	Ben Palanca, Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT03283670
Other Study ID Numbers:	201608024
First Submitted:	November 9, 2016
First Posted:	September 14, 2017
Results First Submitted:	February 9, 2021
Results First Posted:	April 4, 2022
Last Update Posted:	April 4, 2022

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