Effectiveness of Avapro in the Treatment of Salt Sensitivity in Both Normotensive and Untreated Hypertensive Obese African Americans: A Randomized Double Blind Placebo Controlled Trial

Using a crossover design, we will compare the effects of a placebo to an angiotensin II receptor antagonist on the urinary sodium excretion response in obese normotensive subjects and untreated hypertensive African-Americans subjects. We expect that the urinary sodium excretion response to angiotensin II receptor antagonist therapy will be less in the overweight/obese hypertensive subjects compared to the overweight/obese normotensive subjects. This study will also employ a double blind placebo controlled cross-over drug study. Half of the subjects will be normotensive and half drug naïve hypertensive. The normotensive subjects will be identified as described above for Studies 1 and 2. The hypertensive subjects will be identified by Dr. White or his team in the hypertension clinic. These patients will be restricted to those not currently on anti-hypertensive therapy.

This study will involve a screening visit, two first dose visits and two testing weeks over an approximate 5 week period (this includes a one week "washout" period).

Each testing week will have a 3 day salt-controlled diet prior to testing and an approximate 3-hour testing period on Day 4. The 3-hour testing period will include 10 minutes of a baseline rest, 45 minutes of mild stress (competitive video game), and 45 minutes of a recovery rest. A total of 4 blood and 4 urine samples will be collected during the 3-hour period. Each blood draw will consist of about 7 teaspoons for a total of 28 teaspoons per week. If female, a pregnancy test will be performed at the beginning of each testing visit (screening, first dose-1, test day-1, first dose -2 and test day-2) to confirm that they are not pregnant. The week before testing, the subject will come to the Georgia Prevention Institute or Children's Research Unit for the First Dose Visit and meet with one of the study physicians who will give me instructions on how to take Avapro. This appointment will last about 2 ½ hours. They will take their first dose of Avapro or the placebo and will be monitored for the next 2 hours. If female subject, they will provide a urine sample for a pregnancy test to make sure they are not pregnant before they are given the first dose of the study medication. During this time, their blood pressure will be taken every 15 minutes.

During the screening and testing, each subject will be asked to take the MoCA (the Montreal Cognitive Assessment) test in order to measure cognitive thinking after stress. It is a brief 30-question test which takes around 10 minutes to complete. It measures different types of cognitive abilities, including orientation (the approximate position of something/someone), short-term memory (remember information for a short period of time), executive function (planning and problem solving), language abilities (assign appropriate names to appropriate items), and visuospatial ability (determine distance from one object to another). Each question is awarded a particular number of points depending on the accuracy of the answers given. We will be looking to see if the total number of points earned changes in response before and after stress. During the screening visit, they subject will take the MoCA test which will take approximately 10 minutes. Someone from the research team will instruct the subject as to what to do for each question and they will answer each one to the best of their ability.

On testing day, a nurse/phlebotomist will insert a small needle attached to a plastic tube called a catheter into a vein in the hand or arm. This procedure will allow the nurse/phlebotomist to collect the 4 blood samples over the 3-hour testing period. The needle stick may cause some temporary pain and may result in a black and blue mark. A device that automatically takes blood pressure will then be put on the opposite arm. The subject will also be given water to sip on during the duration of testing. Before testing begins, the subject be instructed to take their last dose of medication. During the first 10 minute baseline rest period, they will relax in a reclining chair. They can listen to music, read a book or magazine or watch movies to pass the time. Blood pressure will be taken before and after this 10 minute rest period. Once the baseline rest period is over, a blood and urine sample will be collected.