Drug trial offers hope to diabetics after pancreas removal
Extreme, persistent pain can lead a person to make dramatic decisions, including getting rid of the painful body part.
That's what Vincent Nasser, 28, of Pennsylvania, decided to do last summer.
Entering his senior year at Penn State University six years ago, Nasser began feeling pain and discomfort in his middle and upper back and his stomach, especially after eating.
In time, doctors diagnosed him with idiopathic pancreatitis - inflammation of the pancreas with no known cause. After graduation, he took an information-technology position. But sharp, stabbing pain in the back and torso, sometimes radiating to his legs, required heavy-duty pain medication such as morphine, oxycodone, Percocet, Vicodan and Dilaudid.
Early last summer, ever-progressing levels of pain persuaded Nasser to undergo surgery to remove the entire pancreas. "My life is amazing now compared to having chronic pancreatitis," he says. "I'm living a pretty good life."
The clearly successful surgery did have two drawbacks.
It's a given that once the pancreas is removed, the person must take digestive enzymes orally for the remainder of his or her life. But the larger challenge involves the potential of developing diabetes from the loss of insulin-producing beta cells in the pancreas.
To counter that loss, the pancreatectomy includes saving as many islets from the removed pancreas as possible. Islets are groups of cells consisting mostly of beta cells. The preserved islets then are injected into the portal vein leading to the liver, with the hope that a solid percentage will take refuge in the liver, where they can continue producing insulin and prevent diabetes.
In Nasser's case, the process fell a bit short. He now takes a small daily dose of insulin, but retains some islet function, which makes his diabetes easier to control.
Now there's hope that a new drug can increase islet survival
University of Pittsburgh Medical Centre's new Islet Transplantation Centre, led by director Martin Wijkstrom, is participating in a human clinical trial to test whether the drug, Reparixin, or REP0112, produced by the Italian company Dompe, will increase islet survival following a pancreatectomy.
The drug in previous clinical trials improved outcomes in donor islets transplanted into patients with type 1 diabetes, with better glucose control and insulin independence for three of four patients. The trial also could advance the knowledge and outcomes in transplants using islets from brain-dead donors, Dr Wijkstrom says.
UPMC joins four other medical centres nationwide in the Reparixin clinical trial to measure islet survival and insulin production, following about 100 patients who undergo pancreas removal in the next two years. Dr Wijkstrom said his centre is seeking participants but will accept referrals only from gastroenterologists.
Medical centres at the University of Minnesota (leading the trial), Baylor University, the University of South Carolina and the University of Chicago also are participating.
Removal of the pancreas causes consequences that must be addressed.
At present, 60 per cent to 80 per cent of the islets injected into the portal vein en route to the liver are thought to be destroyed in the process. That can lead to diabetes known as type 3C, which is a more brittle, or hard to treat, form of the disease involving not only insufficient insulin but also the loss of other pancreatic cells and enzymes beneficial to maintaining normal blood glucose levels by interfering with the absorption of nutrients.
Wijkstrom says only one third of the patients who undergo pancreas removal emerge with enough insulin production to prevent diabetes, which helps explain Nasser's results. UPMC does about 12 pancreatectomies a year.
With Reparixin, the hope is that 50 per cent to 70 per cent of islets will survive in the liver, making a larger percentage of patients insulin-independent.
Research has long been under way worldwide to develop the procedure to cure type 1 diabetes with islet-cell transplantation in the liver. But in those cases, the islet cells come from a donor, which means the patient must take immunosuppressant drugs to prevent destruction of the foreign islets.
"So many people with type 1 potentially will benefit," Dr Wijkstrom says. "If we improve outcomes, we could in future transplant two patients with one donor."
Another advantage is that the procedure doesn't require surgery, as would a pancreas transplant. Both pancreas and islet transplants show similar results with 60 per cent success rate after five years.
The US Food and Drug Administration and the Centres for Medicare & Medicaid Services must approve Reparixin as a safe and effective treatment, which in turn would prompt private health insurers to pay for the procedure, Wijkstrom says.
"You should go to your gastroenterologist and ask the doctor if you would benefit from the operation," he says. "Potentially, this could have a big impact. The drug REPO112 could be key because it is designed to help rescue islet cells from being destroyed."
Approaching one year after his pancreas was removed, Nasser says that others might not experience the level of success he has.
"It's not even comparable, before and after the surgery," he says, adding that he suffers no pain and takes no pain medications. "It's a different life now. It's 100 per cent better - the highest percentage you can go."