Georgetown University - Department of Medicine

The area of clinical research has expanded significantly over the last year. With an experienced clinical research staff now in place, we have conducted several clinical research studies written by Division faculty.

Studies under the supervision of Joyce Gonin, MB, ChB include:

A pilot study for the evaluation of the efficacy of intraperitoneal zemplar in the management of secondary hyperparathyroidism (J.M. Gonin).

Treatment of dyslipidemia in end stage renal disease (J.M. Gonin).

The evaluation of leucovorin and serine in the management of hyperhomocysteinemia in patients with End Stage Renal Disease on hemodialysis (J.M. Gonin).

A trial of leucovorin and serine in the management of hyperhomocysteinemia in diabetic patients with end stage renal disease: effect and impact on oxidative stress and endothelial function (J.M. Gonin).

Studies under the supervision of Susan Borgiasz, RN, BSN a full time Clinical Research Coordinator, include the following:

TROPHY
Trial for Prevention Hypertension A Randomized, Double –blind, Placebo-controlled, Multicenter, Long-term Trial of Preventing Hypertension using Candesartan Cilexetil 16 mg in Patients with High Normal Blood Pressure.

This is a 4-year, multicenter, double-blind, randomized, placebo-controlled study, in patents 35 to 60 years old, whose blood pressure (BP) is between 130 mm Hg to 139 mm Hg systolic and/or 85 mm Hg to 89 mm Hg diastolic, to determine if pharmacologic treatment with an angiotensin II receptor blocker (ARD) will reduce the incidence of progression to clinical hypertension (diastolic > or = 140 mm Hg and/or > or = 90 mm Hg.

AMAZE
Antihypertensive Efficacy of Adding Candesartan Cilexetil to Lisinopril in Comparison to Up-titration of Lisinopril: A Multi-center Trial Using ATACAND-ZESTRIL vs. ZESTRIL to Evaluate the Effects on Lowering Blood Pressure-The AMAZE Program

This is an 8-week multicenter, double blind, randomized, parallel-group, forced-titration clinical study to determine the antihypertensive efficacy, safety and tolerability of adding candesartan cilexetil to lisinopril versus up-titration lisinopril in hypertensive patients. This study is a simple, safe, effective and well-tolerated regimen should help physicians to aggressively treat hypertensive patients, as it omits the usual laborious titration steps and multiple blood test monitoring.

Zemplar Capsule/Hemodialysis Patients
A Phase III, Prospective, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study to Evaluate the Safety and Efficacy of Zemplar Capsules in Reducing Serum Intact Parathyroid Hormone Levels In End Stage Renal Disease Subjects on Hemodialysis.

Secondary hyperparathyroidism can and is known to occur in patients requiring dialysis to sustain life. The secondary hyperparathyroidism in End Stage Renal Disease (ESRD) is because the kidneys no longer process and/or produce the active form of Vitamin D which is the mechanism by which bone resorption and formation occurs in the healthy individual. Secondary hyperparathyroidism in patients on dialysis can cause problems resulting in various disorders of the bone formation and resorption and may be accompanied by such conditions as fractures and bone deformities, bone cysts, joint pain, spontaneous tendon rupture, periarthritis and extraskeletal calcification.

This study is testing an active form of vitamin D called ZEMPLAR in its oral form to study how changes parathyroid hormone levels as compared with a placebo (inactive substance). Intravenous Zemplar is currently available and used in hemodialysis units across the country for secondary hyperparathyroidism caused by ESRD. Introduction of a capsule form of Vitamin D will provide a convenient, alternative therapy for physicians and patients who prefer an oral dosage form.

Zemplar Capsule/Peritoneal Dialysis Patients
A Phase III, Prospective, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study to Evaluate the Safety and Efficacy of Zemplar Capsules in Reducing Serum Intact Parathyroid Hormone Levels In End Stage Renal Disease Subjects on Peritoneal Dialysis.

Intravenous Zemplar is currently available and used in hemodialysis units across the country for secondary hyperparathyroidism caused by ESRD. Peritoneal dialysis patients, however, use their peritoneal membrane to dialyze at home and lack a vascular access for intravenous administration of Zemplar. Introduction of a capsule form of Vitamin D will provide a convenient alternative therapy for physicians and patients with ESRD on peritoneal dialysis.

Open Label Study of the Effects of Zemplar™ on ESRD Patients Receiving Maintenance Dialysis with High Turnover Renal Osteodystrophy.

This is a multicenter open label studies evaluating the effect of Zemplar on the Renal Bone Disease of dialysis patients. The study will include 60 patients undergoing bone biopsy before and after onr year treatment with Zemplar. Bone histology data on the effect of Zemplar in dialysis patients. This study will establish its potential benefitial effects and the correlation of histomorphometric parameters with parathyroid hormone, alkaline phosphatase, calcium and phosphorus concentration

AO1-A Phase II, Open-Label, Randomized, Parallel, Titration Study to Determine The Safety and Efficacy of MCI-196 in ESRD Patients With Hyperphosphatemia on Chronic Hemodialysis.

Calcium toxicity has become a major problem in dialysis patients. The major source of Ca is the ingestion of Ca containing phosphorus binders which at present is widely used therapeutic approach. MCI-196 is a phosphorus binder which does not contain Ca. The purpose of this study is to evaluate if this new binder is effective in binding phosphorus and by avoiding a large intake of calcium can diminished the incidence of Ca toxicity. The study will include 150 patients which will be followed for three months.

AO2-A Phase II, Extension Protocol, Of An Open-Label, Randomized, Fixed Dose Study To Determine The Long Term Safety and Efficacy Of MCI-196 in ESRD Patients With Hyperphosphatemia On Chronic Hemodialysis And To Evaluate The Effect of MCI-196 On Cholesterol, Triglycerides And Changes In Arterial And Coronary Calcifications.

This is an extension of previous study which will be extended to ten months. The major goal is to establish if Ca toxicity can be ameliorated by using MCI-196 as a result of avoiding a signicant decrease in the oral Ca load to the patient. This toxicity will be evaluated using the Electron Beam Computed Tomography (EBCT), a new technique wich can detect calcifications in coronary arteries, cardiac valves and other major arteries. An EBCT will be performaed at the beginning, at the fith month and at the end of the study (ten months). In addition since this binder is effective in lowering cholesterol and triglycerides, the potential benefits of lowering this lipids will also be assessed.

AO3-A Phase II, Open-Label, Randomized, Parallel, Titration Study to Determine The Safety and Efficacy of MCI-196 in Diabetic ESRD Patients With Hyperphosphatemia on Chronic Hemodialysis.

This is a study similar to AO!-A but evaluating only dialysis patients due to Diabetes Mellitus. Diabetes is the cause of end stage renal failure leading to dialysis in the US. Diabetic dialysis patients are known to have a higher incidence of cardiac calcifications and an increase in morbidity and mortality as compared with their counterpart non-diabetic dialysis. Thus this study evaluate the ability of MCI-196 in binding phosphorus and avoid calcium toxicity in 150 diabetic dialysis patients.

AO4-A Phase II, Extension Protocol, Of An Open-Label, Randomized, Fixed Dose Study To Determine The Long Term Safety and Efficacy Of MCI-196 in Diabetic ESRD Patients With Hyperphosphatemia On Chronic Hemodialysis And To Evaluate The Effect of MCI-196 On Glucose,Cholesterol, Triglycerides And Changes In Arterial And Coronary Calcifications.

This study is similar to AO2-A but evaluates only diabetic patients on maintenace hemodialysis. Thus, the goal is to evaluate the possible effect of this binder in lowering calcifications, cholesterol and triglycerides. In addition its effect on plasma glucose and glycosilated hemoglobulin will also be assessed.

Oxidative Stress in Hemodialysis Patients; Effects of Valsartan
This is a blinded, within patient, crossover study in hypertensive hemodialysis patients comparing 6 weeks of therapy with an ARB (Valsartan) and with 6 weeks of therapy with a calcium antagonist CA (amlodipine).

We will be evaluating the effects of Valsartan (an ARB) on oxidative stress (marker of metabolic problems) in the hemodialysis patient. Heart disease is increased by several folds in the hemodialysis patient. Traditional risk factors for heart disease include high blood pressure, high cholesterol levels, obesity and smoking; but, they do not appear to contribute to heart disease in dialysis patients. However, non-traditional risk factors that include high homocysteine levels, oxidative stress, clotting disorders, and nitric oxide deficiency have not been well studied in dialysis patients. These factors interact to promote clotting, inflammation and atherosclerosis of the blood vessels. Prolonged administration of an ARB (Valsartan) may prevent oxidative stress and lower the risk of heart disease in patients on hemodialysis. We hope to find that reduction of oxidative stress may be beneficial for protection against cardiovascular disease in hemodialysis patients although there is no evidence at present.

STAAR A Multicenter Study Evaluating Once /every Other Week Subcutaneous Adminsitration of Aranesp™ (darbepoetin alfa) in subjects with Anemia of Chronic Renal Insufficiency (CRI)

The research program is to further investigate the use of Aranesp™ to treat anemia (low red blood cell count) in patients with kidney disease. Additional data will be collected about Aranesp™, including its effective ness and other potential benefits (clinical and economic). If you are a patient with Chronic Renal Insufficiency (CRI), you may be aware if a drug called erythropoietin (abbreviated EPO and commonly called Epogen® and Procrit®) to treat the anemia associated with kidney disease. EPO is a protein that stimulates red blood cell formation. EPO is a protein that stimulates red blood cell formation. To participate in this study, you will be asked to take Aranespä. Aranespä is not an experimental drug, as it was recently approved by the United States Food and Drug Administration (FDA) to treat the anemia associated with kidney disease. Aranesp^TMis a different molecule from EPO, but like EPO it has the ability to stimulate red blood cell formation. However, the potential advantage of Aranesp^TM is that injections (shots) may only be needed once every other week.