The University Record, March 19, 2001

Clinical research program receives $33.6 million grant

By Kara Gavin
Health System Public Relations

The University of Michigan Health System has received a $33.6 million grant—one of the largest of its kind in the nation—from the National Institutes of Health (NIH) to fund its General Clinical Research Center for five more years starting this month.

The award will allow the Health System to continue and strengthen its long tradition of providing a home for cutting-edge clinical research that gives patients access to the latest advances and helps increase knowledge about disease and the human body.

Given by NIH’s National Center for Research Resources in a rigorous competition, the grant funds specialized facilities, staff and resources that support more than 200 clinical studies at any given time. It is the largest grant in the 38-year history of the U-M’s Center. A companion NIH grant will support half the cost of a $1.2 million renovation and expansion, with the other half coming from the Health System in an expenditure approved by the Regents March 15.

The U-M’s Center is among the oldest and largest in the nation’s system of 77 such centers and the only one in Michigan. More than 2,200 adult and pediatric patients come to the Center each year to participate in studies of medical conditions and trials of innovative therapies for everything from cancer and heart disease to sleep disorders and rare metabolic syndromes.

“Every new therapy that reaches the general public today gets there only through multiple steps of clinical research. That research needs a special environment to thrive,” says Health System CEO Gilbert S. Omenn, principal investigator on the Center grant.

“Academic medical centers such as ours generate many new medical discoveries, and our Center provides U-M researchers the space and expertise needed for a comparative advantage in NIH- and corporate-sponsored clinical studies in patients and volunteer participants.”

Adds John Wiley, the Center program director, “This award will provide the Center with additional resources to better assist the University’s life scientists in translating their laboratory findings into new clinical knowledge and innovative therapeutics.”

Wiley and Dorene Markel, the Center’s administrative director, oversee the Center’s activities and 63 staff members. More than 580 researchers are involved with studies at the Center, performing research funded by the NIH, other federal agencies and industry.

All research is overseen by an advisory board and strictly adheres to federal guidelines for studies involving humans. In addition to the main Center grant, the NIH will fund a new Research Subjects Ombudsman based at the Center to oversee patient safety issues and related investigator training.

The Center provides specialized inpatient space, located on the seventh floor of University Hospital and staffed by skilled nurses and physician assistants. The Center includes 16 inpatient beds, where study participants spend more than 3,200 nights a year. Its Metabolic Kitchen and bionutritional staff provide carefully made meals, while an on-site laboratory allows blood and other samples to be collected and analyzed. The Center also provides crucial biostatistical and informatics support to researchers.

Its outpatient clinic, which logs more than 4,000 visits a year, is now located next to the inpatient space but will move to the nearby Med Inn Building.

The grant also will pay for specialized cell-sorting equipment for the Center’s Human Applications Laboratory, where research on gene therapy and immunotherapy agents takes place under the direction of Blake Roessler.

And the funding will help purchase state-of-the-art medical imaging equipment for a new core facility that will allow the Center researchers and others at the Health System to study new ways to see the body’s inner workings. The Biomedical Imaging Core is led by Kirk Frey.

The bulk of the main grant provides core funding for more than 200 clinical studies performed at the Center. Specific project grants, given separately, add another $97 million.

This research addresses dozens of medical conditions and phenomena. For example, Center investigators are currently working to understand or find new treatment strategies for cardiovascular disease; cancers of the lung, breast, liver, lymph nodes, nerve cells, pancreas and skin; diabetes and other hormonal disorders; depression; fibromyalgia; menopause; high blood pressure; thyroid disease; psoriasis; rheumatoid arthritis; childhood cancers; and lupus.

The smaller grant for renovation and expansion will fund the remodeling of the inpatient space, including the dedication of two rooms to sleep research that can track the effects of both diseases and medical interventions on sleep patterns.

The construction funds also will allow the Center’s outpatient facilities to move from the hospital floor to the nearby Med Inn Building, increasing convenience for trial participants whose appointments take less than a day and returning inpatient space to hospital use. The new outpatient space will feature the same number of exam rooms and infusion rooms that the current outpatient Center has, as well as a small specimen lab and satellite bionutrition unit. The emphasis on outpatient visits reflects a growing trend in clinical trial design and medicine in general.

General Clinical Research Center Featured Projects

The General Clinical Research Center at the Health System is home to more than 200 clinical trials each year. The following list of continuing and new projects that will be supported by the new $33.6 million grant exemplifies the broad range of research investigation at the Center.

  • The next step in the clinical evaluation of a “vaccine” against melanoma. The study will measure patients’ response to a technique that uses some of their own master white blood cells, which have been grown from their own stem cells and “trained” to recognize and attack their own cancer cells. In addition to these dendritic cells, as they are called, some patients in the trial will receive interleukin-2, which boosts the immune system even further. The trial, co-directed by James Mule and Bruce Redman, builds on a promising trial already conducted at the Center and on basic research begun in the 1990s.

  • A study of the hormonal mechanisms involved in menopause, led by School of Nursing Prof. Nancy Reame. This research, aimed at understanding how the interplay between different hormones changes as a woman ages and the differences in hormones among women in different stages of life, may eventually lead to better strategies for minimizing menopause’s side effects.

  • An examination of how people react to insulin as they age, focusing on the tendency to become resistant to insulin’s ability to control blood sugar breakdown or regulate blood vessel activity. An understanding of these two kinds of insulin resistance is especially important in the study of hypertension and diabetes. The trial, led by Mark Supiano, will test whether therapies that increase sugar metabolism also can lower blood pressure.

  • A preventive trial designed to test a new strategy for treating chronic hepatitis B, targeted at patients who have had a liver transplant and need help protecting their new liver from the same damage that the virus caused in their original liver. Gastroenterologist Anna Lok will lead a trial that combines the antiviral drug lamivudine with a short or long course of hepatitis B immune globulin after transplant. The research also will look at how hepatitis B comes back to infect the new liver and will test a drug to combat lamivudine-resistant virus.

  • Continued investigation of a radioactive antibody developed at the Health System for use against non-Hodgkin’s lymphoma. The radioimmuno-therapy, which targets tumor cells with lethal radiation while aiming to spare healthy tissue, has shown promise in low-grade lymphoma patients whose cancer has not responded to chemotherapy. A phase II trial led by Mark Kaminski will investigate how well the approach works as a front-line option, including how well it eliminates molecular signs of the cancer.

  • An ongoing examination of how African Americans respond to efforts to lower their blood pressure, specifically looking at the effect on their kidneys. The research, led by Kenneth Jamerson, is using three different anti-hypertension regimens and two different blood pressure targets to assess how well the therapies protect participants’ kidneys against damage. African Americans are more likely than members of other ethnic groups to suffer kidney damage caused by high blood pressure. The Health System project, part of a multi-center trial, aims to help researchers find the reasons for the difference.

  • A unique attempt to measure the concentrations of hormone levels throughout the day and night in the blood of people with fibromyalgia and chronic fatigue syndrome. Both conditions, which cause constant fatigue and, in the case of fibromyalgia, a low pain threshold, are thought to stem from problems with coordination among three of the body’s main glands: the hypothalmus, the pituitary and the adrenal. The study, based on constant blood monitoring and measurement of how extra hormones affect gland performance, will be led by Leslie Crofford and Kevin McDonagh. It may lead to new therapies for both conditions.

  • An investigation, led by John Wiley, of diabetic neuropathy, an abnormality of nerve function that occurs in many people with poorly controlled diabetes mellitus. This study will develop the techniques in humans to monitor changes in sensory nerve function during the development of neural complications. Such techniques will provide the foundation to monitor the effects of novel therapeutic interventions in patients afflicted with or at risk of developing diabetic neuropathy.

  • Several new pilot studies are examining the effect of a drug called tetrathiomolybdate, or TM, as a novel cancer therapy. The drug, which binds to copper in the bloodstream, appears to inhibit blood vessel growth that plays a critical role in tumor progression. U-M researcher George Brewer first developed TM in the 1990s for the treatment of Wilson’s disease, which is marked by an excess of copper in the blood. He also noted its effect on blood vessel formation. Today, newly diagnosed Wilson’s patients from around the world come to the Center to receive TM as the first weapon against their disease. It is hoped that the ability of TM to inhibit blood vessel formation will lead to a safe and effective treatment for a variety of medical problems in which regulating blood vessel growth plays an essential role.