Nitrous Oxide for PTSD (N2OP)

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

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.

Study Overview

• Status: Terminated
• Conditions: PTSD
• Intervention / Treatment: Drug: Nitrous Oxide; Drug: Oxygen; Drug: Saline; Drug: Midazolam; Drug: Nitrogen

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304-1290
      • VA Palo Alto Health Care System, Palo Alto, CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: Oxygen; inhaled gas; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in the Severity of PTSD as Measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5)	Improvement in PTSD severity is measured by the Clinician Administered PTSD Scale DSM-5 (CAPS-5). It measures frequency and intensity of PTSD-related symptoms. For the CAPS-5 the minimum units are 0 and maximum units 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.	1 week

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Carolyn I Rodriguez, MD PhD, VA Palo Alto Health Care System, Palo Alto, CA

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: May 4, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 7, 2020

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: PTSD; Nitrous Oxide
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anesthetics, Inhalation; Midazolam; Nitrous Oxide
• Other Study ID Numbers: MHBB-009-19S; I01CX001789 (U.S. NIH Grant/Contract); 53017 (Other Identifier: IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No data will be shared without approval of sponsor and IRB.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes