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

一氧化二氮治疗创伤后应激障碍 (PTSD)：IIa 期试验

• 批准号: 9891865
• 负责人: Carolyn I Rodriguez
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891865
• 关键词: Acute; Age; Analgesics; Anesthesia procedures; Anesthetics; Biological Markers; Brain; Childbirth; Clinical; Clinical Trials; Cognitive; Computers; Delusions; Dental Care; Drug Kinetics; FDA approved; Functional disorder; Glutamates; Hallucinations; High Prevalence; Hour; Impaired cognition; Impairment; Inhalation; Inhalation Anesthetics; Intervention; Ketamine; Link; Measures; Mediator of activation protein; Memory; Mental Depression; Midazolam; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neurobiology; Nightmare; Nitrogen; Nitrous Oxide; Outcome Measure; Outpatients; Pain; Pain management; Pathway interactions; Phase; Placebos; Population; Post-Traumatic Stress Disorders; Probability; Process; Psychiatric therapeutic procedure; Randomized; Research; Research Design; Safety; Saline; Selective Serotonin Reuptake Inhibitor; Signal Transduction; Symptoms; Testing; Therapeutic; Thinking; Veterans; active comparator; cognitive capacity; cognitive control; comorbidity; daily functioning; depressive symptoms; efficacy testing; evidence base; experience; improved; novel strategies; novel therapeutics; pain outcome; pain symptom; prevent; recruit; reduce symptoms; response; side effect; statistics; symptomatic improvement; treatment response

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 N-methyl-D-aspartate receptor (NMDAR) 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 our 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. Nitrous oxide is FDA-approved for use in anesthesia and pain management, and may be a new approach for managing PTSD. Nitrous oxide’s favorable pharmacokinetics (rapid offset in minutes) prevent the transient cognitive and psychotomimetic side effects (delusions, hallucinations) sometimes seen with other NMDA glutamate modulators. Nitrous oxide may be suited to Veterans in view of: 1) their older age (which brings greater probability of age-associated cognitive impairments), and 2) higher prevalence of co-morbid pain than in the US population. As an anesthetic, nitrous oxide has robust evidence regarding its application in pain, and a superior safety record as an analgesic for dental procedures and childbirth. 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, we will first assess whether nitrous oxide treatment improves PTSD symptoms within 1 week. In parallel, we will explore whether the treatment improves co-existing depression and pain. In addition, we 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. We will test whether the magnitude of nitrous oxide’s effect on PTSD symptoms or pain depends on the Veteran’s baseline capacity for cognitive control or on changes induced in cognitive control. If diminished PTSD symptoms are related to changes in cognitive control, these findings would signal that cognitive control may merit examination in a larger study of mechanism of action. Taken together, if nitrous oxide is found to rapidly relieve Veterans’ PTSD symptoms and modify cognitive and pain outcomes, and these results are replicated in a larger study, it could transform psychiatric treatment of PTSD.

创伤后应激障碍（PTSD）严重扰乱了许多退伍军人的生活。目前的一线治疗，