Control Intervention will be 1 Placebo Capsule given orally, one time

1st Experimental Arm will be 1 capsule of LCZ 696 given orally, one time

Diabetes Mellitus, Type 2

Diastolic Dysfunction

Participants will receive Oral LCZ 696 (Entresto 97/103 mg)

LCZ 696

Participants will receive 1oral Placebo capsule

Placebos

Mayo Clinic in Rochester

PDD in Type 2 Diabetes w/wo Diastolic Dysfunction

Effects of Neprilysin Inhibition With ARNI (LCZ 696) on the Cardiorenal and Humoral Response to Acute Saline Volume Expansion in DM With and Without PDD

The change in plasma cGMP levels from baseline to after volume expansion DM with PDD versus non-PDD

The composite endpoint consisting of sodium excretion, GFR, urinary cGMP and diastolic function change from baseline to volume expansion in Type 2 DM with PDD versus non-PDD

Horng Chen

Professor of Medicine

Mayo Clinic

Placebo-controlled study comparing Oral Placebo with Oral LCZ 696 (Entresto)

Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month

Atenolol tablet(Negative controls, Open-label)

Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month
Aliskiren
Atenolol

Atenolol & Aliskiren

Atenolol tablet(Negative controls, Open-label)
Atenolol

Atenolol

Total

Sex: Female, Male

Analyses of the MRIs were performed using commercial software (Argus version 4.02, Siemens Medical Systems, Germany) by experienced observers who were blinded to patient information. To measure central aortic distensibility, the systolic and diastolic cross-sectional areas were measured by manual contouring of the aorta through the cardiac cycle on the cine image. Distensibility at the four regions was calculated as the mean of values obtained from the following equation: Distensibility = (Amax - Amin)/[Amin × (Pmax - Pmin)](10-3mm/Hg), where Amax is the maximal (systolic) aortic area, Amin is the minimal (diastolic) aortic area, Pmax is the systolic blood pressure (SBP), and Pmin is the diastolic blood pressure (DBP). Central aortic blood pressure measured non-invasively by SphygmoCor was used for systolic and diastolic blood pressure.

Central Aortic Distensibility by MRI

Aortic PWV was measured according to the well-validated method using MRI 19. From the velocity-encoded MRIs, aortic contours were automatically detected and manually adjusted in each slice area throughout the cardiac cycle. The transit time between the flow curves of each region of the aorta was determined from the midpoint of the systolic up-slope on the flow versus time curve 26-28. The up-slopes were identified by drawing a line between the points of 40% and 60% maximum velocity on the waveform. The distance between each aortic level was measured on black blood images using a curved line along the center of the aorta. Based on these data, the regional PWV was calculated as the ratio of the distance between levels and the time differences between the arrival of the pulse wave at each level. The PWV was measured at two regions: the proximal aorta (proximal PWV between level 1 and level 2) and the entire aorta (PWV-total between level 1 and level 4).

Atenolol and Aliskiren

Atenolol tablet(Negative controls, Open-label)
Control group baseline 24 Weeks Central PWV (m/s)(26) by MRI regional PWV A (level 1-2) 3.8 (1.7) 3.6 (1.23) PWV-total (level 1-4) 5.0 (1.03) 4.9 (1.24)

Central Aortic PWV(Pulsed Wave Velocity)

Overall Study

Prof Duk-Kyung Kim

Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month
Treatment (n=14) Overall rate of adverse events 12 (85.7%) moderate to severe cases 0 generalized symptoms 8 (57.1%) gastrointestinal symptoms 4 (28.6%) lung problems 0 cardiovascular symptoms 3 (21.4%) central nervous system symptoms 5 (35.7%) Eye, nose, throat symptoms 4 (28.6%) gynecologic problems 1 (7.1%) problems of extremities 1 (7.1%)

Atenolol tablet(Negative controls, Open-label)
Control (n=14) Overall rate of adverse events 10 (71.4%) moderate to severe cases 2 (14.3%) generalized symptoms 4 (28.6%) gastrointestinal symptoms 3 (21.4%) lung problems 1 (7.1%) cardiovascular symptoms 0 central nervous system symptoms 1 (7.1%) Eye, nose, throat symptoms 1 (7.1%) gynecologic problems 1 (7.1%) problems of extremities 2 (14.3%)

Marfan Syndrome

Aliskiren

Samsung Medical Center

Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS

Comparison Study of the Effect of Aliskiren Versus Negative Controls on Aortic Stiffness in Patients With Marfan Syndrome Under Treatment With Atenolol

Duk-Kyung Kim

PhD, MD, Professor

Heart Failure

All subjects will initially receive 10mg of enalapril and be gradually titrated up to 20mg with blood pressure tolerance for 6 months.

Enalapril

National Cheng Kung University Hospital

Anti-Hypertensive Agent (ACEi) and Heart Function Improvement in Association With Rho Kinase Activity Changes in Human

A Clinical Study on Anti-Hypertensive Agent (ACEi) and Heart Function Improvement

Ping-Yen Liu, MD, PhD, Assistant Professor of Internal Medicine

National Cheng-Kung University Hospital

Hypertension

AVE7688

Losartan-potassium

Sanofi-Aventis Administrative Office

AVE7688 in Patients With Mild to Moderate Blood Pressure

Double-blind, Randomized, Parallel-group, Dose Ranging, Multicenter Study to Evaluate the Efficacy and Safety of 2.5, 10, 35 and 50 mg AVE 7688 Once Daily, Using 100 mg Losartan-potassium Once Daily as Calibrator, for 12 Months Treatment, in Patients With Mild to Moderate Hypertension

angioedema/kalij

PDD in Type 2 Diabetes w/wo Diastolic Dysfunction

Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS

Anti-Hypertensive Agent (ACEi) and Heart Function Improvement in Association With Rho Kinase Activity Changes in Human

AVE7688 in Patients With Mild to Moderate Blood Pressure

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