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Nitrous Oxide for PTSD (N2OP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04378426
Recruitment Status : Not yet recruiting
First Posted : May 7, 2020
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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).
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
Estimated Study Start Date : September 1, 2020
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : September 30, 2023

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Improvement in the severity of PTSD as measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04378426


Contacts
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Contact: Carolyn I Rodriguez, MD PhD (650) 493-5000 ext 60067 carolyn.rodriguez@va.gov

Locations
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United States, California
VA Palo Alto Health Care System, Palo Alto, CA
Palo Alto, California, United States, 94304-1290
Contact: Carolyn I Rodriguez, MD PhD    650-493-5000 ext 60067    carolyn.rodriguez@va.gov   
Contact: Carolyn I Rodriguez, MD PhD    (650) 493-5000 ext 60067    carolyn.rodriguez@va.gov   
Principal Investigator: Carolyn I Rodriguez, MD PhD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Carolyn I Rodriguez, MD PhD VA Palo Alto Health Care System, Palo Alto, CA
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT04378426    
Other Study ID Numbers: MHBB-009-19S
I01CX001789 ( U.S. NIH Grant/Contract )
53017 ( Other Identifier: IRB )
First Posted: May 7, 2020    Key Record Dates
Last Update Posted: June 2, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No data will be shared without approval of sponsor and IRB.

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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
Keywords provided by VA Office of Research and Development:
PTSD
Nitrous Oxide
Additional relevant MeSH terms:
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Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Midazolam
Nitrous Oxide
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anesthetics, Inhalation
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents