Intervention: Hydrochlorothiazide
Trial phase: Phase 2
ATC code: C03AA03 | C03AB03 | C03AX01 | C03EA01 | C09BX03 | C09DX01 | C09DX03 | C09DX06 | C09DX07 | C09DX08 | C09XA52 | C09XA54 | G01AE10
SMILES: NS(=O)(=O)c1cc2c(cc1Cl)NCNS2(=O)=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 11
Group description: Oral, 12.5 mg/day qd, 4 weeks

Hydrochlorothiazide
Eligibility criteria:
Inclusion Criteria:

Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
Systolic blood pressure >/= 130 mmHg and <180 mmHg
Age is > or = 18 and < or = 79 years of age
Weight stable (+/- 5 lbs) for the previous 3 months
Healthy, as determined by health history questionnaire, blood chemistries, 12-lead ECG
Blood chemistries indicative of normal renal (creatinine <2.0 mg/dl), liver (<3 times upper limit for ALT, AST), and thyroid function (TSH between 0.4 - 5.0 mU/L)
If currently receiving treatment with or taking any of the following supplements, be willing and able to discontinue taking them for 2 weeks prior and throughout the treatment period: Vitamin C, E or other multivitamins containing vitamin C or E; or omega-3 fatty acids.
No history of cardiovascular disease (e.g., heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy), Type 1 or Type 2 diabetes, or peripheral arterial disease
Non-smokers, defined as no history of smoking or no smoking for at least the past 1 year
Normal resting 12-lead ECG (no evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter)

Exclusion Criteria:

Systolic blood pressure >/=180 mmHg or diastolic blood pressure >110 mmHg
History of cardiovascular disease such as heart angioplasty/stent or bypass surgery, myocardial infarction, stroke, heart failure with or without left ventricular ejection fraction <40%, cardiomyopathy, valvular heart disease, cardiomyopathy, heart transplantation, Type 2 and Type 1 diabetes
Smoking or history of smoking within past one year
History of gastric ulcers, bleeding disorders, dyspepsia, severe gastroesophageal reflux disease (GERD), or metabolic acidosis
History of chronic obstructive pulmonary disease (COPD)
Abnormal resting 12-lead ECG (e.g., evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter)
Serious neurologic disorders including seizures
History of renal failure, dialysis or kidney transplant
Serum creatinine > 2.0 mg/dL, or hepatic enzyme (ALT/AST) concentrations > 3 times the upper limit of normal
History of HIV infection, hepatic cirrhosis, other preexisting liver disease, or positive HIV, Hepatitis B or C test at screening.
Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
History of recent chicken pox, shingles or influenza (ie., risk of Reye's syndrome)
Recent flu-like symptoms within the past 2 weeks
Pregnant or breastfeeding at screening, or planning to become pregnant (self or partner) at any time during the study. A urinary pregnancy test will be done on all females. If test is positive, the subject will be excluded.
Women with history of hormone replacement therapy within the past 6 months
History of rheumatoid arthritis, Grave's disease, systemic lupus erythematosis, and Wegener's granulomatosis;
Taking lipid lowering (e.g., statins, niacin), glycemic control (e.g. metformin, insulin), anticoagulation, anti-seizure, anti-depression or antipsychotic agents
History of co-morbid condition that would limit life expectancy to < 6 months.
Taking chronic non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, indomethacin, naproxen, acetaminophen (Tylenol), ibuprofen (Advil, Motrin) and not able or willing to go off of for 2 weeks prior and during the study
Taking cox-2 inhibitors (Celebrex, Vioxx, etc) or allopurinol (Zyloprim, Lopurin, Allopurin)
Taking blood thinners such as coumadin (Warfarin), enoxaparin (Lovenox); clopidogrel (Plavix); dipyridamole (Persantine); heparin;
Taking diabetic medications (Metformin, glyburide, insulin, etc.), thiazolidinediones (Avandia, Rezulin, Actos);
Taking steroids or biologics : corticosteroids (prednisone); methotrexate, infliximab (Remicade), etanercept (Enbrel); anakinra;
Taking thyroid medications such as levothyroxine (Levoxyl, Synthroid, Levoxyl, Unithroid); Levodopa;
Taking Phosphodiesterase (PDE) 5 inhibitors (e.g., Viagra®, Cialis®, Levitra®, or Revatio®); PDE 3 inhibitors (e.g., cilostazol, milrinone, or vesnarinone); lithium
May participate if no use of the following medications in the 48 hours prior to experimental visits: naproxen (Aleve), acetaminophen (Tylenol), ibuprofen (Advil, Motrin), other any non-steroidal anti-inflammatory drugs (NSAIDS)
Vulnerable populations (prisoners, etc.)
Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study.
History of alcohol abuse or >10 alcoholic units per week (1 unit= 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 oz alcohol)
On weight loss drugs (e.g., Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanol-amine), or similar over-the-counter medications) within 3 months of screening
Any surgery within 30 days of screening