Carolyn Upton, incontinence study, KING-TV, Seattle
About 13 million American women suffer incontinence and many who turned to surgery are featured in the Patient Profiles on MDND. Often the choice of a polypropylene mesh to hold up the bladder or urethra is a decision they regret.
Carolyn Upton first noticed the embarrassing problem of urinary incontinence in her mid-forties. It was especially a problem when she tried to exercise.
Upton was one of 64 women picked for a study conducted by urologist, Dr. Kenneth Peters who is a professor and chairman of urology at Oakland University William Beaumont School of Medicine and Chief of Urology at Beaumont Hospital in Royal Oak, Michigan.
In an in-office procedure, Dr. Peters took a little piece of muscle from the leg. When cells from the muscle were isolated then grown in a lab, they duplicated into different doses – 10 million, 100 million, 200 million cells. Those cells were then injected to regenerate muscles that had weakened around the bladder which led to the incontinence.
After treatment, up to half of the patients appeared to be cleared of the condition.
Dr. Peters says the outcome depended on the dose. The higher the dose the better the outcome.
Carolyn Upton says she’s her condition is about 80 percent improved. De. Peters tells KING-TV a larger phase III clinical trial is planned.
Dr. Kenneth Peters, Urologist, KING-TV, Seattle
Is not a painful for an embarrassing condition that affects as many as 45 percent of women and urinary incontinence increases with age - 20-30 percent of young women, 30-40 percent of middle-aged women, and up to 50 percent of older women, reports WebMD.
Beaumont Hospital Interview with Kenneth Peters. This comes from the website of the hospital.
Kenneth Peters, MD, Professor and Chairman of Urology, Oakland University William Beaumont School of Medicine and Chief of Urology at Beaumont Hospital talks about a new surgery-free procedure for women.
How did you come up with the theory of taking someone's own stem cells to help with cell therapy?
Dr. Peters: This is really on the basis of cellular therapy. It's like the body heal thy self. It really came out of some previous studies done by Dr. Chancellor and his colleagues in the laboratory in animals looking at seeing if muscle can be regenerated. The whole concept of cellular therapy is that if we can gather a component of your own cells so it's your own body and actually isolate the component of the cell that can regenerate and incorporate into tissue, then we may be able to heal things that have been injured. That's kind of the basic concept of this. This is something that ultimately was translated from the lab but now is being really entered in clinical trials. There are very few studies out there looking at cellular therapy to improve disease. This is our first stab at looking at for stress urinary incontinence.
How does the process works?
Dr. Peters: The nice thing about this is it's all office based. These patients are women with stress incontinence. Stress incontinence is when you cough, sneeze, strain you leak urine. The most common treatment we have for that is sling surgery, which is a surgery where you place a piece of mesh and that supports the urethra. But a lot of people don't want to have surgery. Their symptoms aren't that bad and they don't like the idea of that. We're working with Cook Myosite, which is a group out of Pittsburgh who really has now adopted the technology and have the processing lab. We partnered with them and we started the first study in the United States on the cellular therapy. What we did is we enrolled sixty four women who have failed precious treatments for their stress urinary incontinence. They were enrolled in an approved study where they would come in and they filled out an initial questionnaire, diaries and pad weight so we can you know see the type of incontinence they had. Then if they consented to being in the study they would come into the office and would undergo a small biopsy in the thigh. We would take a little piece of muscle. This is done with a little anesthetic right in the office. It takes a few minutes to do. After taking that muscle we typically just have to put a little tape strip over the site. You usually don't need any sutures or anything. That muscle then is sent to Pittsburgh at the Cook Myosite lab and it undergoes processing. Basically in muscle there are a small percentage of cells that are these really early cells that have the capability to replicate and integrate and that is the very minority of amount of cells that are in that muscle. What the lab does is it isolates a few of those cells and then they expand these cells. Once they isolate the cells they can divide, they'll then grow and they'll make into different doses. This was really a dose escalation study and this study was designed for safety as a primary outcome and then we looked at efficacy as a secondary outcome. About six to eight weeks later we would get a vile back and in that vile there was either ten million, fifty million, a hundred million or two hundred million cells. If you looked at the bottle there was almost nothing in it but then what you did is you just rehydrated that in a little saline. The nice thing about this technology is that right in the office with your own tissue we can draw that up in a syringe and just through a little telescope we can actually look right in to the urethra and inject these into the area of the sphincter. The sphincter would be the muscle that should be controlling their continence and that muscle just isn't working well. So the hope of this trial was that number one it would be safe and that number two we would see some patients improve their symptoms.
What have you found out?
Dr. Peters: The most important thing we found out it was safe. So really there was no serious adverse events patients tolerated it very well and we're very happy it was done in an office setting. When we look at the data again people got different doses and what we found is that the majority of patients had at least a fifty percent reduction in their incontinence episodes which is pretty good. Depending on the dose anywhere from twenty to fifty percent of patients became completely dry. It is something that's given us the knowledge to be able to take this and move forward hopefully with a larger clinical trial to really see if we could get FDA approval for this technology.
Can you go back and do it again for someone who may not have worked for at a lower dose that wants to try it again at a higher dose?
Dr. Peters: The nice thing about once you harvest the cells and then they isolate them, is that they can be stored. Then they'll be able to be taken off the shelf again and regrown. In our future trial our intention is that patients will get a single injection or will get a second injection if they're not where they want to be. The next thing is you can over time be retreated with it and this is something that perhaps even years later you could use the same cells. At least in the early data it seems to be that we can store these for the long term and be able to grow them out and use them again.
What phase of trial are you in right now?
Dr. Peters: This is a Phase II trial and again it was mostly around safety but I think we were very fortunate because we did see clinical benefit. The next trial we really need is a study then that compares the actual injection to a placebo or a sham because that's how you really say that it makes a difference. One thing that we found is that if patients said a week later they were better well that probably really isn't from the injection but most patients didn't get better for three to six months. Which would suggest those cells have incorporated and have now expanded and grown in the sphincter and that's the timeline you would expect people to get better. The nice thing is that it may carry on for a long time because most stress incontinence usually occurs somewhere earlier on in your life, often associated with child birth.
Is Phase III in the works?
Dr. Peters: Right now we just got our twelve month data, which was what our primary end point was and we need now to put the data together. Our next step is to go to the FDA and work with the FDA and the company to agree on a future plan for our Phase III trial. Our hope is that within the next year or so we'll be moving forward with a placebo controlled trial to really get the data that we need to make this technology available.
Based on the Phase II results how does this compare to the other stress urinary incontinence that you've seen?
Dr. Peters: It's really hard to compare because it depends on what patients undergo. If you compare it to the kegel exercises or pelvic floor strengthening exercises all that's dependent a bit on the patients willingness and compliance with doing the exercises and how bad their incontinence is at the start. But I think the fact that up to fifty percent of patients became dry is a really good thing because in our surgical series dry rates range from sixty to seventy percent of patients. So it's not that far off when you look at dry rates.
What is the advantage of this procedure?
Dr. Peters: The advantage is it's your own cells. It's healing thyself, it's not surgical, it's an office based procedure and it's something that is very well tolerated. I think that this is just the first step in this technology because we want then to look at men with stress incontinence after prostate surgery. Then we even have hope in the future to be able to look at the injection of these cells directly into the wall of the bladder for patients who have urinary retention where the muscle of the bladder is weakened over time. We see that more and more as the population is getting older that the bladder fails and then they're only relying on catheters, and perhaps if we can inject cellular therapy into the bladder we can regenerate the muscle and allow them to urinate again. We're really in our infancy in this technology but I think we're very excited that this is the first multi-center trial that has shown some definitely safety and definitely some efficacy in this cellular therapy.
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