Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety/Tolerability of IV Rhu-pGSN as a Pre- or Post-Exposure Intervention to Mitigate Proinflammatory Responses to Decompression After High Pressure in a Hyperbaric Chamber
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
Healthy trained SCUBA divers will be randomized into three groups and exposed to a high-pressure profile in a hyperbaric chamber. The high-pressure profile simulates the pressure at a depth of 30 meters of sea water (MSW) for 35 minutes. In the control group, the subjects will receive intravenous normal saline immediately before and after the high-pressure exposure. The second group will receive intravenous recombinant human gelsolin (rhu-pGSN) 24 mg/kg immediately prior to the exposure, and saline post-exposure. The third group will receive saline pre-exposure and rhu-pGSN post-exposure. Blood samples will be collected at multiple time points pre- and post-exposure to assess levels of inflammatory markers, including interleukin (IL)-1β. Other assessments include screening for gas bubbles, a validated questionnaire to assess the incidence of clinical decompression sickness (DCS), measurement of plasma gelsolin (pGSN) levels, and measurement of anti-pGSN antibodies.
详细描述
This is a prospective, randomized, double-blind, placebo-controlled study in healthy volunteers who have been trained for SCUBA diving.
The study will be performed in the hyperbaric chamber at the University of Maryland. Healthy trained divers will be exposed to a high-pressure profile known to cause decreased plasma gelsolin (pGSN), increased microparticles (MPs), and cytokine changes with no adverse effects such as decompression sickness (DCS). The intervention with recombinant human plasma gelsolin (rhu-pGSN) is patterned after the animal model of DCS where rhu-pGSN administration prior to or after decompression abrogated organ injuries concurrent with inhibiting elevations of MPs and intra-particle interleukin (IL)-1β concentration.
There will be three experimental groups. The control subjects will receive intravenous sterile 0.9% saline immediately before and immediately after the 35-minute 30 meters of sea water (MSW) exposure. A second group will receive intravenous rhu-pGSN 24 mg/kg immediately prior to the high pressure exposure and sterile saline post-exposure. The third group will receive sterile saline prior to the exposure and 24 mg/kg rhu-pGSN post-exposure. Development of DCS is not anticipated based on previous experience with 30 MSW exposure for 35 minutes.
Once informed consent is obtained, the following assessments/procedures will be performed:
- Confirm the potential participant is healthy and has been trained as a SCUBA diver.
- Record medical history, including concomitant medications.
- Perform pregnancy test (urine or blood) for women of childbearing potential.
- Perform vital signs and physical examination.
- Perform EKG.
- Measure CBC and metabolic profile lab tests at local laboratory.
- Collect pretreatment blood samples for measurement of pGSN and analysis of antibodies against pGSN.
- Perform Cardiac Echo for bubbles.
- Collect aliquots of blood for subsequent biomarker assays (including IL-1β, pGSN, nitric oxide synthase [NOS2], tumor necrosis factor [TNF]) and microparticles for analysis.
- If eligibility criteria are satisfied, the subject will be randomized 1:1:1 (rhu-pGSN pre high pressure exposure:rhu-pGSN post high pressure exposure:saline placebo). After reconstitution to 200 mg in a final volume of 5 mL in a 10-mL vial, rhu pGSN is not to be kept at room temperature for >2 hours prior to beginning the IV push. Study drug is administered by an IV push through a 0.2 μm filter. The syringe, filter, and extension tubing for the IV push of study drug are to be connected as close to the subjects as possible. Each subject will receive 2 IV study injections. No subject will receive more than 1 dose of rhu-pGSN.
- Subject will be exposed to high pressure (30 meters salt water [MSW] for 35 minutes) and followed up for 24 hours and again at day 14.
- A well-being questionnaire will be administered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Experienced healthy trained female or male SCUBA divers without known underlying comorbidities
- •Informed consent obtained from subject
- •During the course of the study starting at screening and for at least 3 months after their final study treatment:
- •Female subjects of childbearing potential must agree to use 2 medically accepted and approved birth control methods
- •Male subjects with a partner who might become pregnant must agree to use reliable forms of contraception (i.e., vasectomy, abstinence), or an acceptable method of birth control must be used by the partner
- •All subjects must agree not to donate sperm or eggs
排除标准
- •Any co-morbidity contraindicating SCUBA diving
- •Pregnant or lactating women
- •History of unrepaired cardiac shunt or echocardiographic evidence of patent foramen ovale or atrial septal defect
- •Any active underlying conditions including but not limited to cancer or other illness treated with systemic chemotherapy, immunomodulatory biologics, or radiation therapy during the last 360 days or expected to be treated in the upcoming 120 days
- •Refusal or inability to use adequate contraception
- •Participation in an investigational clinical trial (e.g., device, drug, or biologic) in the previous 30 days
- •Any acute illness or vaccination in the previous 30 days
- •History of alcohol or recreation drug use disorder
- •Known allergy to study drug or excipients
- •Weight >125 kg
- •Unsuitable for study participation, in the opinion of the Investigator
研究组 & 干预措施
Control
Sterile normal saline 0.9% IV immediately prior to hyperbaric chamber exposure, and immediately after exposure
干预措施: Sodium Chloride 0.9% Inj pre-exposure (Drug)
Control
Sterile normal saline 0.9% IV immediately prior to hyperbaric chamber exposure, and immediately after exposure
干预措施: Sodium Chloride 0.9% Inj post-exposure (Drug)
Control
Sterile normal saline 0.9% IV immediately prior to hyperbaric chamber exposure, and immediately after exposure
干预措施: Hyperbaric chamber (Other)
rhu-pGSN pre-exposure
rhu-pGSN 24 mg/kg IV immediately prior to hyperbaric chamber exposure, and sterile normal saline 0.9% IV immediately after exposure
干预措施: Sodium Chloride 0.9% Inj post-exposure (Drug)
rhu-pGSN pre-exposure
rhu-pGSN 24 mg/kg IV immediately prior to hyperbaric chamber exposure, and sterile normal saline 0.9% IV immediately after exposure
干预措施: Recombinant human plasma gelsolin pre-exposure (Drug)
rhu-pGSN pre-exposure
rhu-pGSN 24 mg/kg IV immediately prior to hyperbaric chamber exposure, and sterile normal saline 0.9% IV immediately after exposure
干预措施: Hyperbaric chamber (Other)
rhu-pGSN post-exposure
Sterile normal saline 0.9% IV immediately prior to hyperbaric chamber exposure, and rhu-pGSN 24 mg/kg IV immediately after exposure
干预措施: Sodium Chloride 0.9% Inj pre-exposure (Drug)
rhu-pGSN post-exposure
Sterile normal saline 0.9% IV immediately prior to hyperbaric chamber exposure, and rhu-pGSN 24 mg/kg IV immediately after exposure
干预措施: Recombinant human plasma gelsolin post-exposure (Drug)
rhu-pGSN post-exposure
Sterile normal saline 0.9% IV immediately prior to hyperbaric chamber exposure, and rhu-pGSN 24 mg/kg IV immediately after exposure
干预措施: Hyperbaric chamber (Other)
结局指标
主要结局
Adverse Events
时间窗: 14 days
Incidence, causality, and severity of Adverse Events (graded according to the NCI CTCAE version 5.0)
Interleukin (IL)-1β
时间窗: At baseline, during and after exposure, and afterward at 60, 120, and 240 minutes, at 24 hours, and at day 14
Change from baseline in blood IL-1β levels at 2 hours after hyperbaric chamber exposure
次要结局
- Gas bubbles(At baseline, and 30, 60, 120, and 240 minutes after exposure)
- pGSN levels(At baseline, during and after exposure, and afterward at 240 minutes, at 24 hours, and at day 14)
- anti-pGSN antibodies(Baseline, and at day 14)
- Biomarkers(At baseline, during and after exposure, and afterward at 60, 120, and 240 minutes, at 24 hours, and at day 14)
- Questionnaire(60 minutes after hyperbaric chamber exposure)