ADVERTISEMENT

ADVERTISEMENT

ADVERTISEMENT

Many answer Mayo Clinic's research call

We are part of The Trust Project.

People often choose to be involved in medical studies to make a little cash, but along the way they advance scientific knowledge in areas ranging from heart disease to athletic endurance.

At Mayo Clinic in Rochester, thousands of people volunteer to participate in research studies annually.Participants have become the building blocks of research into human health.

Dr. Sundeep Khosla, dean of clinical and translational science at Mayo Clinic, said hundreds of research studies are underway each day at Mayo Clinic.

Three studies with profound human potential include:

• Use of a person's stem cells derived from his own fat tissue, to repair the heart.

ADVERTISEMENT

• Self-derived stem cells to counteract ALS — the devastating neurological illness commonly known as Lou Gehrig's disease.

• Efforts to develop an artificial pancreas for external wear to help manage diabetes for individuals with Type 1 diabetes, and those with Type 2 who take insulin.

Artificial pancreas

Mayo endocrinologist Dr. Ananda Basu said Mayo's Phase II artificial pancreas study has been completed and the results are being analyzed. Phase II trials study effectiveness and safety.

But Basu said there's a second study underway with just two more study participants. In that study, participants wear devices overnight for several days in a row. The devices deliver insulin and monitor blood sugar. They're electronically connected in a "closed loop" via a cell phone-like device that gives directions to the other two.

During the day, the study participants use the devices in an "open loop" — without the Mayo protocol or the electronic connection between the person's insulin pump and glucose monitor.

"When they're asleep we'll hopefully control their blood sugars well enough overnight, and first thing in the morning, so that their diabetes control will be better during the day," Basu said.

Previous studies have shown when people with either Type 1 or Type 2 diabetes start the day with good glucose control, "the rest of the day goes better," Basu said.

ADVERTISEMENT

Will nighttime use of Mayo's closed-loop artificial pancreas provide better glucose control during the daytime for diabetics using their own open-loop systems?

"That's the premise. That's the hypothesis that we're testing — based on prior data," Basu said. That study is expected to finish by the end of the month.

Mayo has plans for two additional studies.

One is a pivotal Phase III study that will include greater numbers of patients. Phase III studies, according to the U.S. National Library of Medicine , are used to confirm effectiveness, watch for side effects, compare a treatment to other current therapies and to collect data about how to use the treatment safely.

"We are in the process of finalizing the protocol, and sending the protocol to the FDA for approval," Basu said. Patients in the Phase III study will use the closed-loop cell phone-like device at home to control their own insulin pump and glucose monitor.

The algorithm Mayo has devised bases the pump's actions to a person's own, unique needs. If blood sugar rises, the protocol triggers a higher insulin-delivery rate. If blood sugar drops, the protocol slows insulin delivery.

Basu said both he and endocrinologist Dr. Yogish Kudva at Mayo in Rochester have submitted applications to the National Institutes of Health for longer-term, closed-loop studies.

Basu said he personally believes within as few as three or as many as five years the FDA will approve the first artificial pancreas. There are many teams across the country working on such devices, so some other team's could be approved first.

ADVERTISEMENT

In the U.S., there are currently at least three different artificial pancreas devices being tested, he said, while in Europe one or two systems are under development.

The device Mayo investigators plan to ultimately provide is designed to eliminate significant time diabetics currently must devote daily to disease management "so that the patient has more time — to enjoy life," he said.

Studies have shown that a patient on insulin treatment who actively tries to manage his or her disease spends 2.5 to 4 hours every day "trying to adjust their insulin dosing, checking their blood sugars, counting carbs, worrying about what to do when they're exercising, worrying about hypoglycemia, and adjusting their lifestyle and their schedules based on insulin dosing and meals," Basu said.

That's like an extra part-time job, he said.

"We hope that, with this artificial pancreas, apart from getting good control, we take away a huge part of the burden," Basu said.

Will impoverished people be able to afford such a device?

"That's a very important question. That's something we still have to figure out," Basu said. But, he said, most people today, even those who face financial struggles, have some sort of cell phone. Mayo's artificial pancreas uses patients' own insulin pumps and glucose-monitor sensors

Lou Gehrig's disease

A diagnosis of ALS, or Lou Gehrig's disease, carries a dire prognosis, with average post-diagnosis survival of about two to five years.

Lou Gehrig was diagnosed nearly 76 years ago at Mayo Clinic in Rochester.

Mayo professor of neurology Dr. Anthony Windebank and assistant professor of neurology Dr. Nathan Staff said their phase I study testing safety of giving patient-derived stem cells to individuals with ALS has enrolled 22 patients with "no significant adverse events."

A phase II study called "BrainStorm" is currently enrolling patients and has already begun. Phase II studies test both treatment safety and efficacy.

If a phase II study is successful, which is not always the case, phase III can look at larger numbers of patients to check for side effects and verify the effectiveness of the treatment in comparison to others available.

Because there's a lack of strongly effective ALS treatments, if the stem-cell therapy developed by Mayo works to slow ALS progression, even by a few months, it would be seen as a major win for science against a seemingly unforgiving disease.

"We anticipate that the phase I preliminary results will be presented at the American Neurological Association meeting in the fall of 2015, Windebank and Staff said in a joint statement to the Post-Bulletin.

Additional phase II studies have been proposed by Mayo to the FDA that would happen at Mayo in Minnesota, Florida and Arizona.

"We are proposing to carry out a phase IIB study in collaboration with partnering institutions in Sweden (Karolinska Institute), Austria (Paracelsus Medical University) and Ireland (National University of Ireland, Galway and Trinity College, Dublin)," the Mayo researchers disclosed.

Almost 30 patients total have enrolled in Mayo ALS stem cells overall studies so far.

The Mayo Clinic Center for Regenerative Medicine and Mayo benefactors were the main funders of the phase I trial. BrainStorm Cell Therapeutics is funding the phase II trial.

The proposed new phase II trials are seeking FDA Orphan Products Program and European Union funding.

Windebank and Staff emphasized they are "very grateful for patients with ALS and their families for being willing to participate in these clinical trials."

The trials themselves are no cakewalk. They require "multiple" examinations, spinal taps and scans.

"Without the research participants these important studies could not move forward," the professors said. "The patients donate fat tissue from which the stem cells are harvested. They then receive their modified cells by injection into the spinal fluid. By donating their time and energy our patients are making huge contributions to moving the field forward for all patients with ALS."

Heart stem cells

Researchers at Mayo have demonstrated the ability to grow heart cells — that actually beat in a petri dish — from patient-derived tissues.

Their goal is to develop a protocol for taking a tissue sample from a patient with heart disease, grow a supply of that patient's stem cells, trigger the stem cells to develop into heart cells and deliver them back into the patient's body so they can heal that person's heart.

This type of regenerative medicine tries to help the body "heal from within." It was in 2010 that Mayo CEO Dr. John Noseworthy deemed regenerative medicine to be a strategic priority for the clinic.

In 2013, a phase II Mayo research study suggested that stems cells can indeed help heal hearts that have been damaged by heart disease. The study showed dramatic improvement in patient quality of life.

Some patients got standard therapy. Others got standard therapy plus stem cells derived from their own bone marrow.

All the patients in the stem-cell group improved, were able to walk longer distances and had better heart-pumping function.

Such studies, therefore, have profound implications for the future quality of life for widely diverse range of patients and their loved ones.

"I think this is what makes Rochester and Olmsted County unique," said Dr. Sundeep Khosla, dean of clinical and translational science at Mayo. "Between Mayo and the local community, there's a lot of trust and Mayo obviously values that trust."

The research-volunteer/research-team relationship

His colleagues at other research centers express surprise at how quickly Mayo researchers can accomplish studies. That, in large part, is due to the willingness of Mayo patients and community members to participate in studies as much-needed volunteers.

Without that emotional commitment to patients, the community and research that stretches all the way back to Dr. W.W. Mayo and his wife Louise's mortgage on their home to buy W.W.'s first microscope for $600, today's world of research at Mayo would be much different.

Today, researchers want to directly affect quality of life for real people outside the laboratory setting. With aging studies, for example, the goal isn't just to extend lifespan but to "extend what we would call 'health span,'" Khosla said.

When it comes to Institutional Review Board approval of any particular research study, he said, "Mayo leadership does want to see how that's improving on the health of our patients."

"How are we actually transforming how we're taking care of patients?" he said. "Today's research is tomorrow's practice, and that really is the mindset."

Olmsted Medical Center

Mayo Clinic isn't the only research rooster in town.

Olmsted Medical Center's research center has contributed significantly to the understanding of asthma, shingles and a variety of other real-world medical concerns.

OMC researchers developed and tested a protocol for school students with asthma. In the past, a student with an asthma crisis would often get a boost in dosage. But the dose often never wen't back down before the next crisis, perhaps related to seasonal allergies or some other trigger.

The OMC research team showed that students with an asthma action plan do better. Schools keep an asthma action plan on hand for each affected student. If a crisis occurs, the student's physician-ordered plan is followed, including stepping the upped dose back down and proactively boosting dose when seasonal problems are likely.

"There is no other private medical group in the country that is doing what we're doing," said Dr. Barbara Yawn, director of research at OMC.

Yawn plans to retire soon and has been unable to find a new OMC research director to serve as her successor.

"I've been searching for 10 years, so i suppose I've almost given up," she said, hoping aloud that an NIH-funded researcher will "come out of the woodwork" to continue studies in the primary-care setting.

Yawn is also co-director of the Rochester Epidemiology Project, which has provided over the course of 22 years about $18 million in research funding.

In 2014, OMC had the equivalent of 15 full-time employees. But by the beginning of 2015, that number had been cut in half as Yawn prepares to transition.

OMC research triggered every post-partum woman being asked about her emotional state to check for post-partum depression.

Before that, "we were missing over half of the women," Yawn said.

"We were the first study in the U.S. to show that we could improve the outcomes of these women by following them," she said. Now, counseling, medication and other formers of support can be offered because post-partum depression is caught sooner.

So important even health providers volunteer

Jean Feehan, who has been a research nurse for 25 years, has volunteered for the Center for Clinical and Translational Science for a variety of research tests.

So many studies are ongoing at any moment that no nurse could memorize all the working parts, such as drug doses, correct bandages, dosing times, etc. That's why research nurses have "flow sheets" they review before each study participant's test.

Researchers also make videos given intricately specific details about exactly how each study's various steps are to occur. To get accurate data, researchers need study participants to get the same drug dose at the same time under the same circumstances.

"It might seem like an unimportant detail to some people," Feehan said. "But we're doing them all the same so they stay consistent study-to-study."

Study participants can be assured that research staff with medical expertise, who are attuned to reacting to potential disease symptoms or medication side effects, are also skilled at making sure research protocols are followed precisely via the flow sheet.

"It's like a recipe card. It'll go step by step for me and tell me what I need to know," Feehan said.

Nanci Hawley, Clinical Research and Trials Unit nurse manager, said volunteers can participate in research via data from medical records, with no invasive tests; during regularly scheduled surgery, or during research visits to the CRTU at either the Saint Marys or Methodist Campus of Mayo Clinic Hospital.

There's a very elaborate electronic monitoring system that helps her keep track of every study, staffing needs and potential for changes when a patient can't make it, a test runs late or some other issue occurs.

Adaptability is the name of the game for research staff.

"it's a challenge. It's a game we play and it's really 'who's on first?' and 'who's on second,'" Hawley said.

A team of seven researchers might be scheduled to interact with a research participant, one researcher drawing blood samples, another monitoring heart function, etc., while a patient exercises, for example.

What happens if the volunteer among hundreds on that particular day has car trouble that morning? That kind of thing happens more frequently than one might guess.

It's a true research-study juggling act.

"There are reproducible results that need to come out of that," Hawley said.

Healthy volunteers, she said, might have a loved one who deals with the disease being studied. Or, some people want to participate in research because they hope the investigational treatment will make them feel better.

Or, perhaps they hope their role will help produce a treatment that will eventually help them or a loved one.

"You're doing this hoping it'll be helpful to you in the long run," Hawley said. But many study volunteers, she said, "have their own reasons why they participate in research — and we're always grateful that they do."

What to read next
Use of a two-drug combination now make up over half of all abortions in the United States, according to the Guttmacher Institute, an abortion research organization. About 350,000 Google searches using those terms or "abortion pill" were conducted during the week of May 1 to 8, according to the authors of the new research letter. That first week in May is when the Supreme Court's decision that would overturn Roe v. Wade was leaked and widely reported.
When information suggesting that he U.S. Supreme Court may overturn Roe v. Wade leaked in May, internet searches about abortion drugs surged to an all-time high. In this episode of NewsMD's "Health Fusion," Viv Williams checks out a study that explored the issue and shares what the researchers say people and healthcare providers should know.
Ticks are out in full force, waiting for you to walk by so they can hitch a ride and take a bite. In this Health Fusion column, Viv Williams shares how two lovely walks in the woods turned into several days of tick terror. And she gives tips on how to avoid ticks and what to do when one is attached to you.
Condemnations warn of "an Orwellian dystopia" in health care, ask doctors to take a stand against state restrictions set in motion by the ruling.