Intranasal Neuropeptide Y in Clinical Trial in Level Two Trauma Patients for PTSD and Acute Stress Disorder (ASD)
试验速览
- 阶段
- 1 期
- 入组人数
- 117
- 试验地点
- 2
- 主要终点
- Preliminary indication of efficacy of intranasal NPY compared to placebo and no intervention for PTSD
研究概览
简要总结
Level 2 trauma patients admitted to Westchester Medical Center who consent and meet the inclusion criteria will answer a questionnaire, be tested on Beck Anxiety Index, assessed for vital signs and provide blood and urine samples for biomarker testing. before the intervention.
Part 1 Dose Escalation: Subjects will receive a single infusion NPY or vehicle delivered to the upper nasal cavity with an intranasal device. The administration of intranasal NPY will follow the 3 plus 3 model and Fibonacci dose escalation scheme.
Subjects will be assessed for Acute Stress Disorder (ASD) on the National Stressful Events Survey Acute Stress Disorder Sheet (NSESSS) at 3-7 and at 14-30 days post trauma, At >60 days post trauma to be evaluated with the PTSD Symptom Scale Interview for DSM-5 (PSS-I-5) and given the Beck Anxiety Inventory test.
Part 2 Dose Expansion Cohort: Once the maximal tolerated dose (MTD) is determined, we will follow it by a dose expansion cohort to obtain preliminary evidence of efficacy of intranasal NPY to alter the severity of ASD and inhibit the progression to PTSD and the usefulness of several biomarkers.
详细描述
Patients admitted to the Westchester Medical Center as a level 2 trauma patient who meet the admission criteria will be asked to join the study and written consent will be obtained. Every patient who consents to participate will fill out a questionnaire of general information including education level, marital status, social support etc. and administered the Beck Anxiety Inventory. They will be asked to collect urine samples until the next morning.
The next morning at about 9-11 AM vital signs will be measured, including standing systolic blood pressure. Blood and the overnight urine samples will be collected for biomarker testing. This will include urinary norepinephrine levels, plasma ACTH and epigenetic changes in the genes for glucocorticoid receptor and norepinephrine transporter.
Subjects will then receive intranasal NPY (GMP-grade) delivered to the upper nasal cavity with an intranasal device from Kurve. We have chosen this device since it appears to be the best delivery system to the upper olfactory region of the nose for delivery to the brain. It has been used most widely, including the earlier clinical trial with intranasal NPY. After the intranasal NPY, patients will be evaluated for potential adverse reactions and vital signs measured at 30 min, 90 min, and every 4 hrs until released from the hospital. 1 and 3 days after the intranasal infusion.
The dose escalation of intranasal NPY will follow the 3 plus 3 model and Fibonacci dose escalation scheme with a starting dose of 9.6mg, selected based on the highest previously studied dose (Sayed et al. 2018). According to this model if no participant has a dose limiting toxicity (DLT), we will proceed to the next dose. If 1/3 has a DLT, 3 additional participants will be enrolled and if more than 1/6 have a DLT the dose escalation will be terminated.
A DLT will be defined as an adverse event or a clinically significant change in vital signs as follows: (1) any serious adverse event experienced at any time during the study that was determined to be at least "possibly" related to the study drug, or (2) a non-serious adverse event rated at least moderate in severity and at least "possibly" related to the study drug, or (3) occurrence of any of the following changes in vital signs with 90 minutes following administration of the NPY: (i) symptomatic hypotension or >20% decrease in systolic blood pressure (SBP) and an absolute SBP < 90; (ii) symptomatic hypertension or >20% increase in SBP and an absolute SBP >170 or diastolic blood pressure (DBP) > 95; (iii) new onset of tachyarrhythmia (defined as a heart rate >100 bpm) or symptomatic bradycardia (heart rate <60 bpm).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Level 2 trauma patients admitted to the trauma floors or trauma ICU at Westchester Medical Center
- •Experienced fear at the time of the trauma
排除标准
- •Vulnerable populations, such as pregnant women, prisoners, persons with decisional incapacity.
- •History of coronary artery disease, heart failure, prior stroke, heart surgery
- •Bood pressure >160/90
- •Acutely psychotic
- •Current diagnosis of anorexia nervosa, bulimia
- •Current diagnosis of cancer
- •Drug abuse or dependence in the preceding 3 months,
- •Any unstable medical condition
- •Active suicidal/homicidal ideation
- •Cannot speak, read, write and understand English at least at 8th grade level.
研究组 & 干预措施
Placebo
Type two trauma patients randomly assigned to be administered the vehicle (water) with Kurve intranasal device once and followed for up to 60 days afterwards for development of Acute Stress Disorder and Posttraumatic Stress Disorder.
干预措施: Placebo (Other)
Neuropeptide Y
The individuals in this arm will be randomly assigned to be administered intranasal NPY with Kurve intranasal device once and will be followed for at least 60 days afterwards for development of Acute Stress Disorder and Posttraumatic Stress Disorder.
干预措施: Neuropeptide Y (Drug)
结局指标
主要结局
Preliminary indication of efficacy of intranasal NPY compared to placebo and no intervention for PTSD
时间窗: 2-3 years
Rating for likely PTSD on PSS-I-5 a 20 item interview \>60 days after the trauma
Preliminary indication of efficacy of intranasal NPY compared to placebo and no intervention for early Acute Stress Disorder (ASD)
时间窗: 2-3 years
Rating on National Stressful Events Survey Acute Stress Disorder Short Form (NSESS) 3-7 days after traum
Preliminary indication of efficacy of intranasal NPY compared to placebo and no intervention for prolonged Acute Stress Disorder (ASD)
时间窗: 2-3 years
Rating on National Stressful Events Survey Acute Stress Disorder Short Form (NSESS) 14-30 days after trauma
Safety and Tolerability
时间窗: 6-9 months
Dose escalation until treatment emergent adverse effect
次要结局
- Preliminary indication of usefulness of epigentic changes in GR and NET genes to predict development of ASD and PTSD and response to intranasal NPY(3 years)
- Preliminary indication of efficacy of intranasal NPY compared to placebo and no intervention for anxiety(2-3 years)
- Preliminary indication of usefulness of urinary norepinephrine to predict development of ASD and PTSD and usefulness of intranasal NPY(3 years)
- Preliminary indication of usefulness of plasma ACTH to predict development of ASD and PTSD and response to intranasal NPY(3 years)
- Preliminary indication of usefulness of blood pressure to predict development of ASD and PTSD and response to intranasal NPY(3 years)
研究者
Esther Sabban
Professor
New York Medical College