N2OP: Nitrous Oxide for PTSD

Sponsor

VA Office of Research and Development (U.S. Fed)

Overall Status

Recruiting

CT.gov ID

NCT04378426

Collaborator

(none)

104

Enrollment

Location

Arms

23.8

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Post-traumatic stress disorder (PTSD) seriously disrupts the lives of many Veterans. Current first-line treatments, serotonin reuptake inhibitors or prolonged exposure therapy, take weeks to months to bring meaningful improvement, leaving Veterans experiencing prolonged suffering. A promising new treatment approach for rapidly reducing PTSD symptoms is nitrous oxide, an inhalation anesthetic and putative glutamate modulator that diminishes depression symptoms within 1 day and has limited side effects. If shown to be similarly effective in PTSD, nitrous oxide may add dramatically to the treatment armamentarium by bringing rapid symptom decrease before longer-term therapies take hold. The proposed projects test the efficacy of nitrous oxide in relieving Veteran's PTSD symptoms and, in parallel, explore how nitrous oxide may modify cognitive and pain outcomes.

Condition or Disease	Intervention/Treatment	Phase
PTSD	Drug: Nitrous Oxide Drug: Midazolam Drug: Nitrogen Drug: Oxygen Drug: Saline	Phase 2

Detailed Description

The proposed projects will examine the efficacy of nitrous oxide in relieving Veteran's PTSD symptoms and in parallel, explore whether nitrous oxide improves cognitive and pain outcomes. Specifically, the investigators will first assess whether nitrous oxide treatment improves PTSD symptoms within 1 week. In parallel, the investigators will explore whether the treatment improves co-existing depression and pain. In addition, the investigators will explore nitrous oxide's effects on a PTSD-associated impairment that is often overlooked - disruption in cognitive control, a core neurobiological process critical for regulating thoughts and for successful daily functioning.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized placebo-controlled clinical trial including two groups: Experimental (admixture of up to 50% nitrous oxide and 50% oxygen plus IV saline) and Active Comparator (admixture of up to 50% nitrogen and 50% oxygen plus 0.045mg/kg midazolam).Randomized placebo-controlled clinical trial including two groups: Experimental (admixture of up to 50% nitrous oxide and 50% oxygen plus IV saline) and Active Comparator (admixture of up to 50% nitrogen and 50% oxygen plus 0.045mg/kg midazolam).

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Blinding Protections: First, the investigators will separate personnel and location of the team providing study drug from the team performing psychiatric evaluations. Independent evaluators (IEs) blind to treatment assignment will assess participants . Second, records for drug administration will be kept separate from psychiatric assessment case report forms until completion of the study. Third, all participants will be blinded as to the nature of the inhaled gas and IV drug at each session; all participants will be informed that they will receive either nitrous oxide and IV saline or an air mixture with a high nitrogen component and IV midazolam. Integrity of the blinding will be assessed by recording each patient's guess as to which drug was received.

Primary Purpose:

Treatment

Official Title:

Nitrous Oxide for Posttraumatic Stress Disorder (PTSD): A Phase IIa Trial

Actual Study Start Date :

Oct 7, 2021

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nitrous Oxide PTSD participants in this arm will receive and admixture of up to 50%nitrous oxide and 50% oxygen plus intravenous saline	Drug: Nitrous Oxide PTSD participants in this arm will receive and admixture of up to 50% nitrous oxide and 50% oxygen plus intravenous saline Drug: Oxygen inhaled gas Drug: Saline Placebo infusion
Active Comparator: Midazolam PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam	Drug: Midazolam PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam Drug: Nitrogen PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam Drug: Oxygen inhaled gas

Arm

Intervention/Treatment

Experimental: Nitrous Oxide

PTSD participants in this arm will receive and admixture of up to 50%nitrous oxide and 50% oxygen plus intravenous saline

Drug: Nitrous Oxide

PTSD participants in this arm will receive and admixture of up to 50% nitrous oxide and 50% oxygen plus intravenous saline

Drug: Oxygen

inhaled gas

Drug: Saline

Placebo infusion

Active Comparator: Midazolam

PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam

Drug: Midazolam

PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam

Drug: Nitrogen

PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam

Drug: Oxygen

inhaled gas

Outcome Measures

Primary Outcome Measures

Improvement in the severity of PTSD as measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5) [1 week]
Improvement in PTSD severity is measured by the Clinician Administered PTSD Scale DSM-5 (CAPS-5). measures frequency and intensity of PTSD-related symptoms. For the CAPS-5 the minimum units are 0 and maximum units are the total scale are 80. The higher the number on the CAPS-5, the more severe the PTSD symptoms. Response is defined as a change in the CAPS-5 of at least 12 points, which represents meaningful improvement in clinical PTSD symptoms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Veteran
primary diagnosis of PTSD
sufficient severity of PTSD symptoms
capacity to provide informed consent

Exclusion Criteria:

psychiatric or medical conditions that make participation unsafe
pregnant or nursing females
concurrent use of any medications that might increase the risk of participation (e.g. drug interactions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Palo Alto Health Care System, Palo Alto, CA	Palo Alto	California	United States	94304-1290

Sponsors and Collaborators

VA Office of Research and Development

Investigators

Principal Investigator: Carolyn I Rodriguez, MD PhD, VA Palo Alto Health Care System, Palo Alto, CA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

VA Office of Research and Development

ClinicalTrials.gov Identifier:

NCT04378426

Other Study ID Numbers:

MHBB-009-19S
I01CX001789
53017

First Posted:

May 7, 2020

Last Update Posted:

Nov 9, 2021

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by VA Office of Research and Development

PTSD

Nitrous Oxide

Additional relevant MeSH terms:

Stress Disorders, Post-Traumatic

Midazolam

Nitrous Oxide

Study Results

No Results Posted as of Nov 9, 2021