(PSA) (TRANSITIONAL MUSIC) Schmalfeldt: DBS—Deep Brain Stimulation— the placement of electrodes deep into the brain as a treatment for Parkinson's Disease—was approved by the Food and Drug Administration in 1997. The technology was developed by scientists based on discoveries about brain circuitry supported by the National Institutes of Health. To put it simply, DBS acts as something of a pacemaker for the brain—interrupting the errant electrical activity of that portion of the brain caused by a deficiency of dopamine—a chemical produced by the brain that is necessary for smooth muscle movement. Patients who have undergone DBS generally report a reduced need for the drugs they previously took to control their symptoms—and a reduction in the side effects caused by those drugs. Do a search for "deep brain stimulation" at www.clinicaltrials.gov —a website sponsored by the National Library of Medicine— and you'll come back with several studies that either are or will be recruiting patients in the ongoing search for newer, better ways to use DBS to treat such conditions as epilepsy, dystonia, obsessive-compulsive disorder, depression, and—yes—Parkinson's Disease. As I've mentioned in a previous podcast, I am enrolled in such a clinical trial—a Phase I study to determine the safety and tolerability of DBS in early Parkinson's Disease, a condition I've been walking around with since being diagnosed in 2000. You may recall from that previous episode, I made my first visit to the site of the study—the Vanderbilt University Medical Center in Nashville, Tennessee, back in February. After a visit with the study coordinator, the lead investigator, the neurosurgeon who performs the implant surgery, and a biomedical ethicist, I signed the consent forms. Well, on March 25th, I returned to Vanderbilt where I was housed in the General Clinical Research Center—which is funded by a grant from the National Center for Research Resources at the NIH. The NCRR funds a national network of 59 of these GCRC's that provide settings for medical investigators to conduct safe, controlled, state-of-the-art, inpatient and outpatient studies of both children and adults. Dr. David Wilde is a program official in NCRR's Clinical Research Division, and he has oversight of 14 of these GCRC's—including the one at Vanderbilt. He talked about the purpose of the program. WILDE: This is a long-standing grant program, and Vanderbilt is one of the oldest. Some of these grants are in their 47th, 48th year so this is a continuous, ongoing effort. And at Vanderbilt, what the NCRR, the NIH really does is that we sort of buy a piece of the hospital that will later be dedicated to clinical research studies. And we buy the space or rent the space and we buy beds and put outpatient facilities in that space. And then we hire all the personnel that would be needed to run a clinical trial—the nurses, the core lab technicians, everything that you would expect to have in hospital care and we pay their salary and support primarily so that an investigator at Vanderbilt—should they discover something interesting or if they have a particular area of clinical research interest—can go to the GCRC and conduct that trial. And as you know, clinical trials are very expensive.
Schmalfeldt: So the GCRC provides a much-needed base of operations for investigators conducting clinical research. And they also provide many of the comforts of home for the person participating in the clinical trial. For myself, I was quite impressed with the staff at the GCRC at Vanderbilt. You might think the concept of "southern hospitality" is just one of those quaint concepts from days gone by. You'd be wrong. Although the room was small and clinically Spartan, it was cozy as any hospital room could ever be and the staff spared no effort to ensure that I was comfortable. And no wonder. Dr. Wilde at the NCRR told me it takes a special breed of nurse to work in an NIH-funded General Clinical Research Center.
Wilde: These nurses that we have are very special because they are trained not only as nurses, but they are trained as research nurses and actually some of them have further accreditation which allows them to monitor invasive procedures, to really be a tremendous assistant to the investigator who many times can't be on the spot every moment. And so these are very special nurses, and in fact sometimes in hospital surveys they will ask "where in the hospital did you get the best treatment?" Many times, the GCRC always came out on top so that the hospital started excluding the GCRC as part of their list of units when they were sending questionnaires around to the patients. These are such highly-trained nurses and—you're right—they're very friendly and yet they're highly-trained and they really enjoy their work. We have very little turnover in the GCRC unit and I think it's because it's a stimulating environment for them. Not only are they conducting nursing, but they're also integral —they're part and parcel of conducting these trials and they take a real sense of pride in that. Schmalfeldt: No argument from this patient. Even though I actually didn't require a great deal of nursing care for this particular visit, beyond the taking of vital signs and the like, several times each shift, the duty nurse would come by to chat for a few minutes, to see how I was doing in general, to ask what appointments I had that day, and to just offer a welcome bit of human contact. The purpose of this visit? Screening. And to be properly assessed by the neurologist, it was necessary to stop taking my anti-Parkinson's medication for a couple days in advance of the appointment. By the time I visited with lead investigator, Dr. P. David Charles—associate professor and vice-chairman of Neurology at Vanderbilt—I was showing most of the cardinal signs of PD— rigidity, slowness, and problems with balance. Tremor, the symptom that most folks associate with PD, has never really been much of a problem for me. Dr. Charles put me through the paces of the "Unified Parkinson's Disease Ratings Scale" test—which in many respects, I suppose, resembles some of what you might see on one of those police reality shows on TV —"bring your fingers close together, but don't let them touch. Walk to the end of the hallway, turn around, and come back. Open and close your hand as quickly as you can. Now the other one." After the test, Dr. Charles asked me to go ahead and take my medication—something I was more than ready to do at that point—and he'd come back in an hour for a second look. When he returned to my little room at the CRC, I was—as they say in the parlance of Parkinson's—"On." And how! Dr. Charles repeated the testing and this time I breezed through with barely a twitch. Except for some minor rigidity in my right arm, my symptoms were non-existent an hour after taking my meds. This was important, as DBS only works as well as the medication, so if a person doesn't have a good reaction to the meds, there probably will not be a good result from the surgery. After the exam, I had a chance to sit down and talk with Dr. Charles about the study and what they hope to learn.
(TRANSITIONAL MUSIC) Schmalfeldt: First of all, thank you for everything you're doing for people with Parkinson's to bring the day closer to a cure for this thing. I asked you this when we met in February. What got you interested in Parkinson's? Charles: Well, originally, I guess, when I finished my residency training in neurology, I began to think about the subspecialties of neurology that I'd like to do research in, and Parkinson's Disease —movement disorders and related conditions offered one of the greatest chances for advancements in the field of research for that area over the time of my career. So, I knew I wanted to do research in a subspecialty of neurology so Parkinson's Disease is one of the things that certainly posed a significant challenge to patients. But then, I thought, also had potential for significant advancements during my time in research.
Schmalfeldt:"The Safety and Tolerability of Deep Brain Stimulation in Early Parkinson's Disease." What are we trying to prove with this study?
Charles: This study is a first step. It's clearly a pilot study testing deep brain stimulation in the very early stages of Parkinson's Disease. Just to take a step back, DBS therapy has been widely accepted and is a proven therapy for advanced stage Parkinson's Disease, and—in fact—recently in Europe has now been tested in the middle stages of the disease—not FDA-indicated for that, but certainly has been tested and is proving to be helpful. What our study is doing here at Vanderbilt University is to test the device in the very earliest stages of Parkinson's Disease. They hypothesis of the underlying scientific question that we're hoping to get at is could the therapy slow the progression of the disease if it were applied early. Schmalfeldt: That would be big time news.
Charles: It would be big news, it would be certainly. Because there's today there's no therapy that's clearly proven to slow the progression of the disease. Our study currently—the goal is to enroll 30 patients total in a pilot study of safety and tolerability to collect the preliminary data necessary to then begin a large-scale multi-center effort to test that hypothesis of could it slow the progression in Parkinson's long term. Schmalfeldt: And what sort of patients are you looking for in this?
Charles: People with Parkinson's Disease, certainly in the very earliest stages, meaning they have to have been on medication less than four years, between the ages of 50 and 75, also not have any fluctuations in their response. Schmalfeldt: No dyskinesias or any "on and off" times. Charles: Exactly.
Schmalfeldt: Why that cut off? Why "four years"? Charles: Well, typically people begin to experience motor fluctuations, if they're going to have them, within five to seven years of disease onset. So we're trying to get this study in the very earliest stages so less than four years of medication but also without any of those features if they were to develop earlier than expected. Schmalfeldt: Thanks again for your interest in Parkinson's. Charles: Thank you so much for participating and having us on.
(TRANSITIONAL MUSIC) Schmalfeldt: During our visit, Dr. Charles was accompanied by Ms. Chandler E. Gill, the study coordinator, the first person I contacted at Vanderbilt concerning my possible participation in this study. We talked about what it means to be the coordinator of a clinical trial.
Schmalfeldt: You're the coordinator for this clinical trial. Not just this clinical trial, you coordinate many here at Vanderbilt, right?
Gill: That is correct.
Schmalfeldt: That sounds like a hard job. That sounds like trying to keep a bunch of balls in the air at the same time— "herding cats" if you will. What's involved with being a coordinator for a clinical research trial? Gill: It starts with putting all the regulatory paperwork through. There are things like the Institutional Review Board. And then, for this trial, because it's not a currently approved use of the device, we have to go through the FDA to get an investigational device exemption. And then, after all the regulatory aspects are completed, then there's patient recruitment, scheduling patients for appointments, and all the various stages of the study, for example for this one there are the four screening appointments then the baseline, six month, 12-month, 18-month and 24-month stays in the CRC. Schmalfeldt: As somebody on the other end of this, you guys have been extremely accommodating. When you're looking for patients, are there many that you have to just turn away right at the outset? Gill: There are many that we turn away just because you can see right off the bat that they don't qualify—they're too young for the study or they've been on medication too long or something like that. Schmalfeldt: And what's your interest in neurology? Gill: Well, I did an internship with Dr. Charles when I was in college and after I graduated he offered me a job. So I plan to work here for another two years and then apply to medical school.
Schmalfeldt: Are you going to be a neurologist?
Gill: Maybe. (Laughter) Schmalfeldt: We'll hold out a good thought. (Laughter) Now, if folks are interested they contact you directly.
Gill: That's right. Schmalfeldt: Why don't you give us that e-mail address? Gill: OK. My e-mail address is chandler.e.gill@vanderbilt.edu.
Schmalfeldt: Thank you, again, so much for everything you guys are doing.
Gill: Thank you.
(TRANSITIONAL MUSIC) Schmalfeldt: There was more screening, more testing to be done. Later that afternoon I visited with Dr. Michael G. Tramontana, assistant professor of psychiatry and neurology at Vanderbilt. It was his job to make sure that I wasn't suffering from any cognitive disabilities that would make me ineligible for the surgery or the study. Then on Wednesday, I chatted with Dr. Ronald M. Salomon, associate professor of Psychiatry. His business was to make sure I wasn't suffering from depression and was —in fact—entering into the study with a clear mind and for the right reasons. It wasn't on the official schedule, but I also had a very interesting conversation with Dr. Peter Konrad, Associate Professor of Neurosurgery and Biomedical Engineering. He's the gent who will become intimately familiar with my brain should I be randomized for the surgical portion of the study—you'll hear our chat in an upcoming podcast. Next step? On April 10, I'll return to Vanderbilt for the first of the eight day stays at the CRC that you heard Ms. Gill talk about. For eight days, I will be taken off my medication and each day I will be rated according to my performance in the Parkinson's Disease Rating Scale. I'll be videotaped for future reference. Then at the end of the eight days, it's a metaphorical flip of the coin. Heads? I'm scheduled for surgery. We'll talk about that next time. Tails? I go to the control group. That means I continue taking the same meds I'm taking now. and I go back to Vanderbilt twice a year, eight days at a time, for the next two years so my progress can be compared to the folks who were randomized to the surgical group. April 18. That's the day I'll find out which group I'm going to. And that will determine what direction my experience in this very important clinical trial will take. And I'll share the verdict with you in our next episode of NIH Research Radio. Now, choosing to participate in a clinical trial is a very personal decision. In my case, I'm excited about the possible neuroprotective effect of deep brain stimulation, meaning that if the theory is correct, it could slow down the inevitable advancement of this relentlessly progressive disease. DBS is not a cure for Parkinson's, but is has been shown to be an effective treatment. And it's completely reversible should the happy day arrive where an effective cure is discovered. Also, whether I'm in the surgical group or the control cohort, there's a sense of satisfaction in knowing that I'm contributing to research that could, someday, improve the lives of the more than 1-point-5 million Americans with Parkinson's Disease, with approximately 60-thousand new cases diagnosed each year. Now, if you're considering taking part in a clinical trial, talk it over with your family doctor or specialist and your loved ones. Then check out www.clinicaltrials.gov to see if there's a trial that fits your situation. There's a need for healthy volunteers, as well as for those diagnosed with a variety of conditions. The journey of discovery begins with a single step. You can make that step by logging on to www.clincialtrials.gov.
(THEME MUSIC) Schmalfeldt: And with that, we come to the end of this episode of NIH Research Radio. Please join us on Friday, April 20th when episode 30 of NIH Research Radio will be available for download. These stories are also available on the NIH Radio News Service website: www.nih.gov/news/radio. Our daily 60-second feature, NIH Health Matters is heard on nearly a thousand radio stations nationwide, as well as on XM Satellite Radio, the HealthStar Radio Network and online at www.federalnewsradio.com. If you have any questions, comments or suggestions, please feel free to contact me. the info is right there on the podcast web page. If we use your comment, we'll send you something nice from the NIH gift shop! That e-mail address: ws159h@nih.gov —once again, our e-mail address is ws159h@nih.gov. I'm your host, Bill Schmalfeldt. NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland. an agency of the US Department of Health and Human Services.
(MUSIC FADES)
