PTSD
Conditions
Keywords
PTSD, Nitrous Oxide
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.
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.
Interventions
DRUGNitrous Oxide
PTSD participants in this arm will receive and admixture of up to 50% nitrous oxide and 50% oxygen plus intravenous saline
DRUGMidazolam
PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
DRUGNitrogen
PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
DRUGOxygen
inhaled gas
DRUGSaline
Placebo infusion
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, 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.
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nitrous Oxide PTSD participants in this arm will receive and admixture of up to 50%nitrous oxide and 50% oxygen plus intravenous saline
Nitrous Oxide: PTSD participants in this arm will receive and admixture of up to 50% nitrous oxide and 50% oxygen plus intravenous saline
Oxygen: inhaled gas
Saline: Placebo infusion | 1 |
| Midazolam PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
Midazolam: PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
Nitrogen: PTSD participants in this arm will receive and admixture of up to 50%nitrogen and 50% oxygen plus intravenous 0.045mg/kg midazolam
Oxygen: inhaled gas | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Nitrous Oxide | Midazolam | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 49 years STANDARD_DEVIATION 0 | — | 49 years STANDARD_DEVIATION 0 |
| CAPS 5 | 64 units on a scale STANDARD_DEVIATION 0 | — | 64 units on a scale STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | — | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | — | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | — | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | — | 0 Participants |
| Region of Enrollment United States | 1 participants | — | 1 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
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.
Time frame: 1 week
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrous Oxide | Improvement in the Severity of PTSD as Measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5) | 46 units on a scale | Standard Deviation 0 |