Long Term Antihypertensive Exposure and Adverse Metabolic Effects: PEAR Follow-Up Study
Condition: Drug Induced Hyperglycemia; Secondary Hyperlipidemia
MeSH terms: Hyperglycemia; Hyperlipidemias
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a research study of the long term effects on blood sugar and cholesterol of blood
      pressure lowering medications. People are invited to participate in this research study if
      they participated in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR 1,
      NCT00246519 or PEAR 2, NCT01203852) study and are still taking a thiazide diuretic. In PEAR,
      the effects on blood pressure, blood sugar, and cholesterol of the high blood pressure drugs
      hydrochlorothiazide and atenolol over an 18 week period were evaluated. This PEAR follow-up
      study will determine the effects of thiazide diuretics on blood sugar and cholesterol, but in
      the period since the PEAR trial. The study hypothesis is that long term exposure to thiazide
      diuretics results in larger increases in blood sugar and cholesterol levels than short term
      exposure.
    

Detailed description: 
      One in three deaths in the United States is due to cardiovascular (CV) disease. One in three
      US adults has hypertension, a major underlying cause of CV disease. Type 2 diabetes (T2D) and
      dyslipidemia are major contributors of CV morbidity and mortality among hypertensive
      patients. Thiazide diuretics and beta blockers are first line agents in the treatment of
      hypertension, but these commonly prescribed antihypertensive classes can contribute to
      dysfunction of glucose and lipid metabolism. In randomized controlled trials, reductions in
      CV outcomes due to blood pressure reduction with thiazide diuretic and beta blocker treatment
      are accompanied by increases in T2D incidence and exacerbation of dyslipidemia. CV morbidity
      and mortality resulting from persistent antihypertensive-related T2D or dyslipidemia may
      eventually outweigh benefits from blood pressure reduction, encouraging use of alternate
      antihypertensive classes especially in high risk patients. An accumulating body of published
      literature supports that adverse metabolic effects are induced by thiazide diuretics and beta
      blockers. However, the vast majority of evidence for adverse metabolic effects of
      antihypertensive drugs utilizes secondary analyses of data from randomized blood pressure
      reduction trials. To date, no published study has compared short and long term adverse
      metabolic effects of antihypertensive therapy in the same patient population. The
      Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study is a randomized,
      parallel assignment trial to determine genetic influences on blood pressure response to the
      thiazide diuretic hydrochlorothiazide and the beta blocker atenolol. The PEAR study duration
      (18 weeks) is not sufficient to assess long term effects (over six months) of these
      antihypertensive medications. The primary aim of this study is to determine the effects of
      long term thiazide and beta blocker therapy on glucose and lipid metabolism in the PEAR
      population, in which short term effects have been assessed. Secondary analyses of this
      follow-up study include investigating adverse metabolic effects of long term thiazide
      diuretic and beta blocker therapy on insulin sensitivity and the role of potassium and uric
      acid in the hyperglycemic effects of thiazide diuretics.
    

Intervention name(s): Oral Glucose Tolerance Test
Intervention type(s): Drug
Intervention description(s): Administration of 75 gram oral glucose load and three plasma glucose measurements (including baseline).
Other intervention name(s): Glucose Drink 100
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic