The purpose of this limited competition is to continue patient follow-up and complete the two ongoing HALTPolycystic Kidney Disease (PKD) clinical trials. Tufts-NEMC and the subcontracted site at BIDMC are two of seven patient enrolling sites for HALT-PKD. The HALT-PKD Trials are comprised of two studies (A &B) and are both currently in the patient enrollment phase. HALT-PKD Study A is evaluating the impact of reninangiotensin- aldosterone system (RAAS) blockade on progression of disease in 548 hypertensive PKD patients with estimated glomerular filtration rate (GFR) >60ml/min/1.73 m2. In Study A, the effect of study medication on structural progression at two different levels of blood pressure control is assessed using a 2x2 factorial design. Accordingly, 548 hypertensive ADPKD participants are randomized to one of four study arms: 1) combination ACE-I/ARB with standard blood pressure (BP) control (systolic 120-130 and diastolic 70-80 mm Hg);2) ACE-I monotherapy with standard BP control;3) combination ACEI/ ARB treated to a low BP target (systolic 95-110 and diastolic 60-75 mm Hg);and 4) ACE-I treated to the low BP goal. Other antihypertensive agents are added as needed to meet the BP goals. The primary endpoint of the study is the percent change in total kidney volume, as measured by magnetic resonance imaging (MRI) over time. HALT-PKD Study B is evaluating the impact of RAAS blockade on progression of disease in 472 hypertensive PKD patients with estimated GFR 30-60 ml/min/1.73 m2. The primary endpoint of Study B is a composite endpoint of time to the 50% reduction of baseline estimated GFR, ESRD (initiation of dialysis or preemptive transplant), or death. All 472 hypertensive ADPKD participants are treated to a standard level of blood pressure control (systolic 110-130 mm Hg and diastolic 80 mm Hg), with addition of other antihypertensive agents as needed. This application will describe in detail the two participating clinical centers including the investigators and study teams;adherence to the study protocol;quality and safety of study procedures;and efforts being made to achieve the targeted recruitment goal of 137 study A and 118 study B subjects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK062411-12
Application #
8477030
Study Section
Special Emphasis Panel (ZDK1-GRB-N (O1))
Program Officer
Flessner, Michael Francis
Project Start
2002-08-15
Project End
2014-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
12
Fiscal Year
2013
Total Cost
$885,503
Indirect Cost
$263,088
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
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Porath, Binu; Gainullin, Vladimir G; Cornec-Le Gall, Emilie et al. (2016) Mutations in GANAB, Encoding the Glucosidase IIα Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease. Am J Hum Genet 98:1193-207
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Schrier, Robert W; Abebe, Kaleab Z; Perrone, Ronald D et al. (2014) Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 371:2255-66
Alam, Ahsan; Perrone, Ronald D (2013) Left ventricular hypertrophy in ADPKD: changing demographics. Curr Hypertens Rev 9:27-31
Torres, Vicente E; Chapman, Arlene B; Perrone, Ronald D et al. (2012) Analysis of baseline parameters in the HALT polycystic kidney disease trials. Kidney Int 81:577-85
Menon, Vandana; Rudym, Darya; Chandra, Priya et al. (2011) Inflammation, oxidative stress, and insulin resistance in polycystic kidney disease. Clin J Am Soc Nephrol 6:7-13

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