Providence Medical Research Center plans to begin enrolling patients next month for a clinical study to determine whether an experimental drug improves the kidney function of patients who suffer severe diabetic kidney disease.

Dr. Katherine Tuttle, lead researcher here on the study, says the research also will monitor the effects that the drug, currently called FG-3019, has on patients' cardiovascular function, because many people with chronic kidney disease also have serious cardiovascular problems that might be improved by the medication. In addition, the study will look at ways to improve overall diagnosis of diabetic kidney disease, Tuttle says.

The center here will be one of about 50 sites nationally that will be involved in the study, of which Providence Medical Research is the primary site, on behalf of the developer of the drug, San Francisco-based biotech company FibroGen Inc., Tuttle says. The study is what's called a Phase II clinical study, which means the drug already has gone through Phase I research in which it's given to laboratory animals, and now can be tested on a number group of humans. Phase III studies would involve many more, possibly thousands, of humans, Tuttle says.

Patients with advanced diabetic kidney disease often have a condition called albuminuria, which is characterized by excess protein in their urine because their kidneys' filtering function has deteriorated. It's hoped the experimental drug will ease that condition.

Diabetic kidney disease is the most common cause of end-stage renal disease, and contributes to cardiovascular disease risk. In any given year, 20 percent of patients who have less than normal kidney function because of the condition die, Tuttle says.

"They have received the best care available, but are at high risk of kidney failure and death," she says.

Tuttle says studies such as this one—which could have a significant positive impact on high-risk patients who haven't been helped by other therapies—are a good fit for Providence Medical Research Center, because one of its major goals is to conduct research that will benefit patients who need it most. Also, she says, the study targets a major public health problem.

About 12 percent of the U.S. population has chronic kidney disease, and about half of those cases are due to diabetes. The rate is even higher among minority groups, she says.

About two-thirds of the people on kidney dialysis have diabetes, Tuttle says. Participating in studies such as this one is helpful in bringing awareness to and seeking treatments for some of the major diabetes-related health issues, and affords researchers the opportunity to perform so-called "proteomic" research. Such studies look for new biomarkers to help improve diagnosis of kidney disease and to measure the results from clinical trials, she says.

In the Phase II study, about 150 patients with advanced kidney disease nationwide will be given one of two study doses of FG-3019 or a placebo by infusion every two weeks for six months. Between five and 10 of those patients will be selected in the Spokane area, Tuttle says.

While on the drug, patients will be tested regularly to measure the amount of protein in their urine, and also will have their cardiovascular function tested.

About half of all kidney disease patients develop albuminuria, Tuttle says. The condition, also called proteinuria, is due in large part to excess scar tissue developing in small capillaries in the kidney called glomeruli, hampering the filtering system.

Because of the excess scarring, the urine carries more protein (albumin) as it leaves the body. A moderate increase in protein in the urine is referred to as microalbuminuria. At that stage, kidney function has not yet been significantly affected, and the condition is easily reversible, Tuttle says. Once the disease progresses to the more dangerous stage called macroalbuminuria, kidney function declines, and a patient is not very likely to return to a healthy state, Tuttle says.

To be enrolled in the study, patients must be diagnosed with macroalbuminuria, but not end-stage renal disease, Tuttle says.

"We want to identify people at high risk, but still at a stage where" the kidneys' function could be improved if they're given FG-3019, she says.

The drug is an antibody that reduces the production in the kidney of one of the predominant types of scar tissue by altering the actions of connective tissue growth factor (CTGF), hopefully resulting in improved function of the kidneys' filtering system, Tuttle says. In patients with diabetic kidney disease, CTGF can trigger too much scar tissue formation.

While study patients are being treated with the drug and their urine samples are being monitored, the researchers also will be searching for more possible biomarkers for diabetic kidney disease.

Dr. Radica Alicic, one of the co-investigators here in the study, along with Tuttle and Dr. Sandeep Saha, says a genetic variation determines whether a patient will develop albuminuria as a symptom of diabetic kidney disease, making it difficult to diagnose the disease early in patients who don't have albuminuria.

During the study, researchers also will measure patients' cardiac function, because people who have diabetes and macroalbuminuria are more likely to die from cardiovascular disease than from kidney failure, a fact Tuttle says few people realize.

"I say, 'If you have diabetes and you make it to dialysis, congratulations,'" Tuttle says.

Because of high blood sugar and other factors, patients with diabetic kidney disease frequently develop a condition referred to as aortic stiffening, which is associated with hypertension, heart failure, and death in diabetic patients, Tuttle says. FG-3019 appeared to combat the condition, by improving heart muscle function in phase I animal trials, Tuttle says. If evidence is found that the drug has similar positive effects on cardiac function in humans, that aspect of it could be tested further later.

Tuttle says one of the problems with kidney disease is that it follows a slow progression and people often don't really feel that badly physically until their condition has become very advanced.

"The kidneys are so important and there are so many redundant systems that they can limp along until you're nearly dead," she says.

Depending on results from the FG-3019 study, FibroGen could seek to collaborate with a pharmaceutical company to develop the treatment further and proceed to a larger, Phase III clinical trial involving many more patients, Tuttle says.