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    Targeting Sickle-Cell Pain

    Ward Hagar, M.D., explores leading-edge pain relief for sickle-cell patients.

    Ward Hagar, MD studying sickle cell anemia.
    "Thanks to REDI, everything has gone very smoothly so far. It's quite impressive."

    Ward Hagar, M.D., is currently working on a phase III double-blind, randomized, placebo-controlled study sponsored by the National Institutes of Health to determine whether nitric oxide inhalation is effective in the acute treatment of sickle-cell pain. This is an international multicenter study with four participants currently enrolled at Alta Bates Summit Medical Center and 93 enrolled studywide.

    While current therapies simply mask sickle-cell pain, this study focuses on treating the underlying cause of the tremendous pain crises sickle-cell patients suffer from. If nitric oxide therapy proves to be effective and safe, it could be life changing for people who have this inherited blood disease. Ideally, sickle-cell patients could carry a supply of nitric oxide with them and administer it upon onset of symptoms, alleviating pain immediately and eliminating the need for emergency room visits.

    Interview with Wade Hagar, M.D.

    Your study focuses on sickle-cell pain. Why were you interested in this aspect of the disease?
    Dr. Hagar:

    Sickle-cell anemia is a pretty devastating disease for many people who have it, with 85 to 90 percent of hospital admissions caused by severe pain. The pain is just horrific. It's probably best described as glass scraping against bone. If you just touch the skin, people scream. And anything that stresses you can set off these pain attacks, which are called crises. They come out of the blue, and you're just incapacitated. Stress can come from school, work, or just daily living, so it's difficult to get through life. And there's really no good treatment for it. The pain is a type of neuro-inflammatory pain. Narcotics help a little bit, but they're really just Band-Aids because they don't prevent the inflammatory damage that is causing the pain. They don't really address anything that's going on—they just help you get through it.

    You're exploring the use of nitric oxide. Why that therapy in particular?
    Sickle Cell Anemia cells.
    Dr. Hagar:

    Over the last several years, the focus of sickle-cell research has moved from the red cell to the lining of the blood vessel, called the endothelium. It appears that it's really endothelial dysfunction that's setting up a lot of these problems.

    Your body produces a chemical called nitric oxide, a cell-signaling molecule, but in sickle-cell patients, this whole nitric oxide system is quite dysregulated. Several lines of research led to the thinking that perhaps inhaled nitric oxide, given acutely, could help with sickle-cell pain.

    The research that's going on with REDI is actually part of an international study testing the hypothesis that if you can inhale nitric oxide during the early part of a sickle-cell crisis, you can right the ship of endothelial dysfunction and restore normal blood flow and normal blood vessel function. This should reduce the neuroinflammation.

    Nitric oxide is a gas, so you just put on a little mask at the onset of symptoms and breathe it in. And it seems to be safe. We're watching to make sure that safety profile continues, but it doesn't seem to have any bad effects. If this proves effective, it would be a huge breakthrough.

    Why did you decide to partner with REDI on this project?
    Dr. Hagar:

    I'd been trying to get this study up and running at Alta Bates Summit for several years, but until REDI came along, it just couldn't be done because there were too many departments that had to be pulled together. I'd go meet with one or the other, and we just couldn't coordinate all the different persons, departments, logistics, and regulations. So this would not have happened if it weren't for REDI. They were on the ground and were able to coordinate all of the different departments—pulmonology, respiratory, critical care, nursing, the Emergency Department, and probably others that I'm completely unaware of—to get this study up and running.

    I've gone from not being able to get anything done to everything going smoothly with REDI, so it's absolutely a night-and-day difference.

    What other tasks is REDI helping you with?
    Dr. Hagar:

    REDI is helping with the logistics of getting patients into the study. When sickle-cell patients come in to the Emergency Department, we have to screen them quickly to make sure they qualify for the study, and then get them up to the intensive-care unit for the first 12 hours—not because they're any sicker, but they just need very intensive nursing to draw all of the blood and to monitor all of the things that need to be monitored for the study. And to get that all set up is quite a feat. Thanks to REDI, everything has gone very smoothly so far. It's quite impressive.

    Wade Hagar, M.D.

    REDI is also handling the massive amount of paperwork that has to be filed, and they do it with such good grace and aplomb. They're incredibly well organized, and everything is always organized and set up when I meet with them. I'm very impressed because they just opened REDI, but they're already at a level of proficiency that I'm happily surprised by.

    What is the primary challenge that you face as a medical researcher in a hospital setting?
    Dr. Hagar:

    Any kind of true clinical research carried on in a hospital is challenging because hospitals are so stretched in terms of providing care and meeting other needs. Anything that interrupts that flow, even with the best of intentions, is almost impossible to do on a consistent basis.

    And that's why a group like REDI is so important. They're keeping everyone on their radar screen, and they're helping out when any glitches come along. I've done many other research studies, but this is the first one I've done with REDI. I'm impressed by them. Everything is so well coordinated. They really understand research, and they're able to keep the ball rolling.