PTSDPhase 2N2OPNCT04378426

Nitrous Oxide for PTSD

A Phase 2 study testing Nitrous Oxide, Midazolam and Nitrogen in people with PTSD, run by VA Office of Research and Development at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: PTSD
What is being tested?: Nitrous Oxide, Midazolam and Nitrogen
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: 1 siteUnited States
Study dates: 7 Oct 2021to 31 Aug 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

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

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: PTSD
Being tested: Nitrous Oxide, Midazolam, Nitrogen, Oxygen, Saline
Keywords: PTSD, Nitrous Oxide
Medical subject headings: Stress Disorders, Post-Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Nitrous OxideDrug
PTSD participants in this arm will receive and admixture of up to 50% nitrous oxide and 50% oxygen plus intravenous saline
MidazolamDrug
PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
NitrogenDrug
PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
OxygenDrug
inhaled gas
SalineDrug
Placebo infusion

Study groups in NCT04378426
Study group	Role	What they receive
Nitrous Oxide	Experimental	PTSD participants in this arm will receive and admixture of up to 50%nitrous oxide and 50% oxygen plus intravenous saline Receives: 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 Receives: Drug: Midazolam; Drug: Nitrogen; Drug: Oxygen

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Oct 202131 Aug 2022

First posted7 May 2020
Study start7 Oct 2021
Primary completion31 Aug 2022
Study completion31 Aug 2022

Why it stopped: Use of VA hospital research space is indefinitely delayed due to prioritization of clinical cases delayed by COVID

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for PTSDStudies of the same condition, open and under way.
More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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 blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04378426
Sponsor's protocol ID: MHBB-009-19S
Other IDs: I01CX001789, 53017
Acronym: N2OP
Status last verified: Mar 2023
First submitted: 4 May 2020
Last updated: 3 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: No data will be shared without approval of sponsor and IRB.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Early Intervention for Postpartum PTSD: Comparing Written Exposure and Capnometry-Guided Breathing Therapy
Written Exposure Therapy, Breathing Techniques
Not yet recruiting
RISE for PTSD and Substance Use Disorder in Veterans
Stress Disorders, Post-Traumatic, Substance-Related Disorders
Not yet recruiting
Multimodal Intervention for Individuals With Posttraumatic Stress Disorder (PTSD) and Hazardous Alcohol Use
Post Traumatic Stress Disorder PTSD, Hazardous Alcohol Use
Recruiting
Recovering Sleep After Trauma
Post-traumatic Stress Disorder
Not yet recruitingPhase 2
Written Exposure Therapy Plus Adjunctive Methylphenidate Treatment for Veterans With PTSD
PTSD - Post Traumatic Stress Disorder

All PTSD trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nitrous Oxide for Posttraumatic Stress Disorder (PTSD): A Phase IIa Trial
ClinicalTrials.gov ID: NCT04378426
Acronym / sponsor ID: N2OP / MHBB-009-19S
Conditions: PTSD
Keywords: PTSD, Nitrous Oxide
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Use of VA hospital research space is indefinitely delayed due to prioritization of clinical cases delayed by COVID
Enrolment: 1 participants (actual)
Lead sponsor: VA Office of Research and DevelopmentUS federal agency
Study start: 7 Oct 2021 (actual)
Primary completion: 31 Aug 2022 (actual)
Study completion: 31 Aug 2022 (actual)
First posted: 7 May 2020 (actual)
Results: Posted 3 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2
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).

Arm	Type	Receives
Nitrous Oxide	Experimental	Drug: Nitrous Oxide, Drug: Oxygen, Drug: SalinePTSD participants in this arm will receive and admixture of up to 50%nitrous oxide and 50% oxygen plus intravenous saline
Midazolam	Active comparator	Drug: Midazolam, Drug: Nitrogen, Drug: OxygenPTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Nitrous OxidePTSD participants in this arm will receive and admixture of up to 50% nitrous oxide and 50% oxygen plus intravenous saline	Drug	Nitrous Oxide
MidazolamPTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam	Drug	Midazolam
NitrogenPTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam	Drug	Midazolam
Oxygeninhaled gas	Drug	Midazolam, Nitrous Oxide
SalinePlacebo infusion	Drug	Nitrous Oxide

Primary outcome

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). 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.

Results and safety

Results posted to the registry on 3 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Nitrous Oxide	1	1
Midazolam	0	0

Primary outcome: Improvement in the Severity of PTSD as Measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5)

Time frame: 1 week. Mean (Standard Deviation). Unit: units on a scale

Measure	Nitrous Oxide n = 1	Midazolam n = 0
Value	46 (0)	–

Population analysed: 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.

Adverse events

Time frame: 1 week. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nitrous Oxide	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Midazolam	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No. No data will be shared without approval of sponsor and IRB.

Related trials for PTSD

Recruiting
Early Intervention for Postpartum PTSD: Comparing Written Exposure and Capnometry-Guided Breathing Therapy
Written Exposure Therapy, Breathing Techniques
Not yet recruiting
RISE for PTSD and Substance Use Disorder in Veterans
Stress Disorders, Post-Traumatic, Substance-Related Disorders
Not yet recruiting
Multimodal Intervention for Individuals With Posttraumatic Stress Disorder (PTSD) and Hazardous Alcohol Use
Post Traumatic Stress Disorder PTSD, Hazardous Alcohol Use
Recruiting
Recovering Sleep After Trauma
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Not yet recruitingPhase 2
Written Exposure Therapy Plus Adjunctive Methylphenidate Treatment for Veterans With PTSD
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Carolyn I Rodriguez, MD PhD principal investigator

VA Palo Alto Health Care System, Palo Alto, CA

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nitrous Oxide, Midazolam and Nitrogen in people with PTSD, run by VA Office of Research and Development at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Improvement in the Severity of PTSD as Measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5) (time frame: 1 week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04378426.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2023.