Clinical trial NCT00925119: Examining Genetic Influence on Response to Beta-Blocker Medications in People With Type 2 Diabetes
Official title: Uncoupling Protein Polymorphisms and Cardiometabolic Responses to Beta-Blockers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes
Atenolol
Genetic
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-06-19
Enrollment: 31
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Beta-blockers are medications used to treat cardiovascular disease (CVD) symptoms, including high blood pressure and chest pain. People with diabetes who receive beta-blockers may experience adverse health effects, but the exact cause of why this happens remains unknown. This study will examine the genetic factors that may influence how atenolol, a beta-blocker medication, affects fat breakdown, blood sugar levels, and heart function in people with type 2 diabetes.

Detailed description: People with diabetes who develop CVD have worse health outcomes than people without diabetes who develop CVD. Beta-blockers are medications used to treat high blood pressure, angina (i.e., chest pain), arrhythmias, and other CVD conditions. While beta-blockers are effective at treating these conditions, they may also have damaging effects on cholesterol or glucose levels, thereby possibly lessening their ability to prevent CVD events in people with diabetes. It is important to identify which patients may not benefit from receiving beta-blocker medications. Genetic factors may influence how people respond to beta-blocker medications. The purpose of this study is to evaluate the influence of genetic variation on beta-blocker-induced changes in insulin sensitivity, fat breakdown, and heart function in people with type 2 diabetes.

This study will enroll people with type 2 diabetes. At a series of up to three baseline study visits, participants will have a blood collection, a glucose tolerance test, an echocardiogram to obtain images of the heart, and biopsies of muscle from the thigh and fat from the stomach. All participants will then receive atenolol once a day for 8 weeks. During Week 1, participants will receive a low dose of atenolol. They will then attend a study visit at the end of Week 1, and study researchers will examine how well participants are tolerating the medication. If the atenolol is well tolerated, the dose will be increased. Study researchers will call participants 1 week after any dosage changes to monitor for side effects. Blood collection will occur again at a study visit at Week 4. At Week 8, participants will then attend up to three study visits for repeat baseline testing. Participants will then be slowly tapered off of atenolol over a 1-week period.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* Pre-Diabetes

Exclusion Criteria:

* Insulin therapy
* Treatment with any beta-blocker in the 30 days before study entry
* Asthma
* Chronic obstructive pulmonary disease (COPD)
* Greater than first degree heart block
* Heart rate less than 60 bpm
* Systolic blood pressure less than 90 mm Hg
* Raynaud's phenomenon
* Known history of angina, heart attack, heart failure, coronary revascularization, or automatic implantable cardioverter defibrillators
* Pregnant
* Creatinine clearance less than 35 ml/min
* Hematologic dysfunction (white blood cell \[WBC\] count less than 3000 or hematocrit less than 28%)
* Allergy to amide anesthetics

Primary outcomes:
measure: Change in Diastolic Function (Annular Tissue Velocity [Em])
timeFrame: 8 weeks
measure: Change in Free Fatty Acid Kinetics
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Change in Triglycerides
timeFrame: Baseline and Week 8
measure: Change in Insulin Sensitivity
timeFrame: Baseline and Week 8
measure: Change in Glucose Effectiveness
timeFrame: Baseline and Week 8
measure: Change in HDL
timeFrame: Baseline and Week 8
measure: Change in Insulin
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Amber L. Beitelshees, PharmD, MPH
role: PRINCIPAL_INVESTIGATOR
References: