Rhu-pGSN to Mitigate Proinflammatory Responses to Decompression in Healthy SCUBA Divers

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:

1. Confirm the potential participant is healthy and has been trained as a SCUBA diver. 2. Record medical history, including concomitant medications. 3. Perform pregnancy test (urine or blood) for women of childbearing potential. 4. Perform vital signs and physical examination. 5. Perform EKG. 6. Measure CBC and metabolic profile lab tests at local laboratory. 7. Collect pretreatment blood samples for measurement of pGSN and analysis of antibodies against pGSN. 8. Perform Cardiac Echo for bubbles. 9. Collect aliquots of blood for subsequent biomarker assays (including IL-1β, pGSN, nitric oxide synthase \[NOS2\], tumor necrosis factor \[TNF\]) and microparticles for analysis. 10. 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. 11. 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. 12. A well-being questionnaire will be administered.