Clinical trial NCT01409434: Long Term Antihypertensive Exposure and Adverse Metabolic Effects: PEAR Follow-Up Study
Official title: Long Term Antihypertensive Exposure and Adverse Metabolic Effects: PEAR Follow-Up Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Drug Induced Hyperglycemia
Secondary Hyperlipidemia
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2011-08-04
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

Eligibility criteria: Inclusion Criteria:

* previously enrolled in PEAR study
* completed last PEAR study visit greater than 6 months prior
* receive thiazide diuretic continuously since PEAR enrollment

Exclusion Criteria:

* pregnancy

Primary outcomes:
measure: Fasting Glucose (mg/dL)
timeFrame: Fasting glucose was obtained at time 0 min.
Secondary outcomes:
measure: Oral Glucose Tolerance Test (mg/dl h)
timeFrame: one oral glucose tolerance test was performed with 3 time points (0 hour, 1 hour, 2 hour)
measure: Triglycerides (mg/dL)
timeFrame: Triglycerides was obtained at time 0 min.
measure: Low Density Lipoprotein (mg/dL)
timeFrame: Low Density Lipoprotein was obtained at time 0 min.
measure: High Density Lipoprotein (mg/dL)
timeFrame: High Density Lipoprotein was obtained at time 0 min.
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida College of Pharmacy
state: Florida
Study officials:
affiliation: University of Florida
name: Rhonda M Cooper-DeHoff, PharmD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Jason H Karnes, PharmD
role: STUDY_DIRECTOR
References: