Evaluating the Effect of Aliskiren Versus HCTZ on Coronary Flow Reserve in Hypertensive Type II Diabetics

This study focuses on diabetic patients who are already on any blood pressure-lowering
medication (excluding Tekturna) in addition to either an ACE inhibitor or an ARB (angiotensin
receptor blocker) and still have a blood pressure greater than 130/80 mm Hg. The purpose of
the study is to compare the effects of two different blood pressure treatment regimens, each
containing three medications, on heart function in diabetics with uncontrolled hypertension.
The two treatments are 1) lisinopril (an ACE inhibitor that works by reducing blood pressure)
plus amlodipine (a calcium channel blocker that reduces blood pressure) plus aliskiren (a
renin inhibitor, which also reduces blood pressure), or 2) lisinopril plus amlodipine plus
hydrochlorothiazide (a diuretic, or "water pill"). Participants will have their coronary flow
reserve - which is a measure of coronary vessel function, a predictor of future
cardiovascular events - and a number of cardiovascular biomarkers in blood and urine at
baseline and after 6 months of treatment. In this manner hydrochlorothiazide will be compared
with aliskiren, which researchers think will have a better effect on heart artery blood flow.

Inclusion Criteria:

- Age 18-85

- Diagnosed with Type II Diabetes and Hypertension

- Taking either ACE or ARB in addition to any other antihypertensive medication
excluding aliskiren

- Blood Pressure >130/80

Exclusion Criteria:

- Serum Potassium >5.2 mmol/L

- History of any cardiovascular event (stroke, TIA, unstable angina, CABG, percutaneous
coronary intervention, hospitalization due to HF) during the 3 months prior to Visit
1.

- History of MI

- Documented ejection fraction of <50%

- Hypertension (at Screening): any patient with msSBP ≥ 180 mmHg or msDBP ≥ 110 mmHg

- Congestive Heart Failure NYHA class III and IV

- Concomitant treatment with two (2) or more renin-angiotensin-aldosterone system
blocking agents, e.g. ACE inhibitor, ARB or aldosterone-antagonist.

- Unstable serum creatinine

- Second (II) or third (III) degree heart block without a pacemaker

- Concurrent potentially life threatening arrythmia or other uncontrolled arrythmia

- Clinically significant valvular heart disease

- Known renal artery stenosis

- Any surgical or medical condition which might significantly alter the absorption,
distribution, metabolism, or excretion of the study drugs including, but not limited
to, any of the following:

- History of major gastrointestinal tract surgery such as gastrectomy,
gastroenterostomy, or bowel resection (patients with previous bariatric surgery>6
months prior to Visit 1 are allowed to participate).

- Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic
function/injury as indicated by abnormal lipase or amylase.

- Evidence of hepatic disease as determined by any one of the following: SGPT value
exceeding 3x Upper Limit of Normal (ULN) at Visit 1, a history of hepatic
encephalopathy, a history of cirrhosis, esophageal varices, or a history of
portocaval shunt.

- History of malignancy other than basal cell skin cancer that is likely to reduce the
subject's life span to less than 2 years.

- Any concurrent life threatening condition with a life expectancy less than 2 years

- History or evidence of drug or alcohol abuse with the last 12 months

- Any surgical or medical condition, which in the opinion of the investigator, may place
the patient at higher risk from his/her participation in the study, or is likely to
prevent the patient from complying with the requirements of the study or completing
the study.

- History of hypersensitively to any of the study drugs or to medications belonging to
the same therapeutic class as the study drugs as well as known or suspected
contraindications to the study drugs

- History of noncompliance to medical regimens or unwillingness to comply with the study
protocol

- Use of other investigational drugs at the time of enrollment, or within 30 days or 5
half-lives of enrollment, whichever is longer

- Any condition that in the opinion of the investigator would jeopardized the evaluation
of efficacy or safety

- Persons directly involved in the execution of this protocol

- Pregnant or nursing (lactating) women

- Women of Child Bearing Potential unless post menopausal for at least one year,
surgically sterile or using effective methods of contraception as defined by local
Health Authorities.