Long Term Antihypertensive Exposure and Adverse Metabolic Effects: PEAR Follow-Up Study

Drug Induced Hyperglycemia Clinical Trial

Official title:

Long Term Antihypertensive Exposure and Adverse Metabolic Effects: PEAR Follow-Up Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01409434
• Other study ID #: PEAR Follow-Up
• Status: Completed
• Phase: Phase 4
• First received: August 1, 2011
• Last updated: October 10, 2014
• Start date: June 2010
• Est. completion date: August 2013

Study information

• Verified date: October 2014
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Drug Induced Hyperglycemia
• Hyperglycemia
• Hyperlipidemias
• Secondary Hyperlipidemia

Intervention

Drug:
• Oral Glucose Tolerance Test
Administration of 75 gram oral glucose load and three plasma glucose measurements (including baseline).

Locations

Country	Name	City	State
United States	University of Florida College of Pharmacy	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fasting Glucose (mg/dL)		Fasting glucose was obtained at time 0 min.	No
Secondary	Oral Glucose Tolerance Test (mg/dl h)	Area under the curve for the OGTT was calculated for each patient using the 3 time points (0 hour, 1 hour and 2 hour). Average value for participants is provided.	one oral glucose tolerance test was performed with 3 time points (0 hour, 1 hour, 2 hour)	No
Secondary	Triglycerides (mg/dL)		Triglycerides was obtained at time 0 min.	No
Secondary	Low Density Lipoprotein (mg/dL)		Low Density Lipoprotein was obtained at time 0 min.	No
Secondary	High Density Lipoprotein (mg/dL)		High Density Lipoprotein was obtained at time 0 min.	No