Nitrous Oxide for PTSD

NCT04378426 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: MHBB-009-19SI01CX00178953017
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

PTSD

Keywords

PTSD; Nitrous Oxide

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Nitrous Oxide

EXPERIMENTAL

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

Drug: Nitrous Oxide; Drug: Oxygen; Drug: Saline

Midazolam

ACTIVE COMPARATOR

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; Drug: Nitrogen; Drug: Oxygen

Interventions

Nitrous Oxide DRUG

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

Nitrous Oxide

Midazolam DRUG

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

Midazolam

Nitrogen DRUG

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

Midazolam

Oxygen DRUG

inhaled gas

Midazolam; Nitrous Oxide

Saline DRUG

Placebo infusion

Nitrous Oxide

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1290, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Nitrous Oxide; Midazolam; Nitrogen; Oxygen; Sodium Chloride

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Elements; Chalcogens; Chlorides; Hydrochloric Acid; Chlorine Compounds; Sodium Compounds

Limitations and Caveats

The study was terminated in partnership with program officer given that the nitrous oxide administration space in the hospital (which had been used pre-pandemic) is longer available - it is being used exclusively for clinical care to keep up with the clinical backlog of cases due to the pandemic. This delay will continue for the foreseeable future. COVID-19 has had far-reaching impact on the feasibility of the study, which will not meet its recruitment goal in the foreseeable future.

Results Point of Contact

• Title: Carolyn Rodriguez, MD, PhD
• Organization: Palo Alto VA

carolyn.rodriguez@va.gov

650-493-5000

Study Officials

• Carolyn I Rodriguez, MD PhD

  VA Palo Alto Health Care System, Palo Alto, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 7, 2020
• Study Start: October 7, 2021
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: March 3, 2023
• Results First Posted: March 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)