Research News

•   FYI Research: New office created to streamline clinical trials
•   Bioengineered heart muscle could aid research

FYI Research: New office created
to streamline clinical trials

Clinical trials at Carolina are bigger than you might think. With more than 300 industry-sponsored clinical trials bringing in more than $34 million in funding in fiscal year 2001, clinical trials at Carolina are growing rapidly — up from $11 million in fiscal year 1998.

These trials contribute to important discoveries in the safety and efficacy of drug development, treatment and procedures. For example, John Buse, associate professor of medicine and director of the Diabetes Care Center, is involved in a clinical trial called NAVIGATOR, which monitors family members of diabetics to find out whether or not they develop diabetes. “We randomize them to a blood pressure drug or placebo and to a diabetes drug or placebo and follow them for a period of about six years to see first whether we can prevent the development of diabetes, and second, whether we can reduce the risk of dying of a heart attack or stroke,” Buse said.

Since clinical trials are an important and growing part of research at Carolina, a new Office of Clinical Trials (OCT) is being developed to facilitate smoother processing. John Case, associate vice chancellor for research and interim director, describes the new office as a “one-stop shop for PIs and their sponsors.”

In other words, OCT will “perform all administrative, budgetary, legal and regulatory processing functions for all clinical trials,” Case said. A more efficient, centralized office will make it easier to get the growing number of new clinical trials under way. The new office will not only coordinate the processing of clinical trials but also will provide training and standardize policies and procedures for managing the clinical trials process.

OCT was created with the input of two committees, one headed by Eugene Orringer, professor of medicine, who has conducted many clinical trials at the University, and the other headed by Susan Ehringhaus, vice chancellor and general counsel. In addition to using their own experience with clinical trials, they visited similar offices at other universities such as the University of Texas at Galveston and Columbia University to develop a plan for Carolina’s office.

The new office will have two project managers — one for private industry and one for the federal government. These people, when appointed, will serve as the contacts for the principal investigators, their sponsors, the clinical research coordinators and departmental business managers.

In the future the office hopes to expand to meet other needs of investigators and coordinators based on information received from those who use the office in the first year. “We want to be open to ideas about serving our customers, the clinical researchers, and sponsors,” Case said.

OCT currently is located at 440 W. Franklin St. and will move to Chase Hall in the early fall. It will move closer to the health affairs area when renovations there are complete.
For more information, visit the Office of Clinical Trials web site at research.unc.edu/oct/ or call 843-2698.

Provided by Research and Graduate Studies
Writer: Mary Alice Scott
Editor: Neil Caudle

Bioengineered heart muscle
could aid research

The collaboration between cardiologist and orthopedist may at first seem novel, if not odd. But just such an interdisciplinary connection at the University has yielded potentially useful fruit: a bioengineered, rhythmically beating experimental model of heart muscle.

The new model system is a bioartificial trabeculum, or BAT. Trabecula are thin sections of cardiac tissue within the inner surface of the heart’s main pumping chambers. Although still some distance away from any human clinical application, the model could prove a valuable scientific tool for exploring cardiac disease, including electrical and mechanical disturbances of the heart.

Details of the heart tissue model were presented Aug. 5 to the World Congress of Biomechanics in Calgary, Canada.

“The purpose of our study was to explore the possibility that one could take isolated heart cells and under proper conditions allow them to coalesce and attach to each other in a functional way, thereby creating an artificial tissue,” said cardiologist and co-developer Wayne E. Cascio, associate professor of medicine.
Cascio said the idea for the BAT originated with a biomedical engineering lecture by Albert J. Banes, professor of orthopedics.

Banes had spoken about his work on the development of artificial tendons. Through a company he founded 18 years ago, Flexcell International in Hillsborough, Banes had developed a special tissue plate that has proven a useful framework in which cells in a liquid collagen gel could remodel on their own to form a more tissue-like structure. Other work elsewhere has involved rigid structures or lattices upon which cells attach and grow.

“The fundamental basis for that company was a flexible bottom culture plate with the thought that all cells in tissues in our body are subjected to some forms of mechanical load, cyclic tension being one of them,” Banes said. “We thought it would be better to grow cells in a dynamic environment, on a flexible substrate. We could then stretch the tissue cells in a certain way to simulate the effects of mechanical loads on tendon, muscle bone, ligament and cartilage and also add the shear stress that occurs during fluid flow in blood vessels. Cascio very astutely thought we could grow cardiac myocytes and make a cardiac muscle tissue-like material to test in culture. And that’s where the collaboration began.”

In developing the tissue model, Cascio and his laboratory assistant Joseph Brackhan isolated cardiac myocytes from one-day-old rats. These were mixed in a solution of collagen and serum and allowed to gel under incubation in a Flexcell Tissue Train Plate. The tissue train plates have two nylon tethers at opposite ends of each well and a flexible silicon rubber bottom. After four days in culture, the heart cells migrated toward the center of the gel to form a dense cord of tissue that extended between the two tethers.

The tissue strand rhythmically contracts at 100 beats per minute, easily observed with a low-power microscope. Tests reveal striations characteristic of cardiac tissue and cell-to-cell coupling also characteristic of cardiac tissue.

The team’s long-term goals are to apply this system to study the effects of mechanical loading on normal cardiac physiology and to develop a model system for the study of cardiac illnesses such as congestive heart failure.

“In my lab, we’re specifically interested in generating cardiac myocytes with certain electrical or contractile properties by manipulating the genetics of the cells and then re-forming them into functional tissue to assess their properties,” Cascio said.
He added that some researchers might view this model as a means to generate tissue patches that might be applied to the surface of the heart or to incorporate into a diseased heart — cardiomyoplasty, a kind of cardiac plastic surgery. “But this would be a very early stage of such an approach,” he said.

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