Examining Genetic Influence on Response to Beta-Blocker Medications in People With Type 2 Diabetes
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|ClinicalTrials.gov Identifier: NCT00925119|
Recruitment Status : Terminated
First Posted : June 19, 2009
Results First Posted : December 22, 2017
Last Update Posted : January 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus, Type 2||Drug: Atenolol||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Uncoupling Protein Polymorphisms and Cardiometabolic Responses to Beta-Blockers|
|Study Start Date :||December 2009|
|Actual Primary Completion Date :||June 2013|
|Actual Study Completion Date :||May 2014|
Participants will receive atenolol for 8 weeks.
12.5 mg twice daily of atenolol for 1 week; increased to 25 mg twice daily for a total of 8 weeks, if the medication is well tolerated
- Change in Diastolic Function (Annular Tissue Velocity [Em]) [ Time Frame: 8 weeks ]
- Change in Free Fatty Acid Kinetics [ Time Frame: Baseline and Week 8 ]Estimate of peripheral lipolysis using modeling of free fatty acid levels collected during an IV glucose tolerance test. The change in threshold for insulin action (post-atenolol minus pre-atenolol) is the primary variable from this modeling that we analyzed.
- Change in Triglycerides [ Time Frame: Baseline and Week 8 ](Post atenolol triglycerides - Pre atenolol triglycerides)
- Change in Insulin Sensitivity [ Time Frame: Baseline and Week 8 ]
As measured by the Homeostatic model assessment of insulin resistance (HOMA2-IR) (post atenolol - pre atenolol).
he Homeostatic model assessment (HOMA) is a method for assessing insulin sensitivity from fasting glucose and insulin. A higher HOMA value indicates higher insulin resistance. The widely-used formulae available for HOMA1 provide only linear approximations of HOMA_%B and HOMA_IR, the inverse of HOMA_%S. These are: HOMA1_IR = [FPI (uU/ml) x FPG (mmol/l) ]/22.5 HOMA1_%B = (20 x FPI)/(FPG - 3.5) The results obtained for HOMA2 may differ considerably from HOMA1 computer-calculated values, especially for more extreme glucose and insulin values. For this reason, no attempt has been made to provide linear approximations of HOMA2 calculated values of HOMA_%B, HOMA_IR and HOMA_%S. The software needed to calculate HOMA2 values is available on this website: https://www.dtu.ox.ac.uk/homacalculator/download.php, subject to the conditions specified on the downloads page.
- Change in Glucose Effectiveness [ Time Frame: Baseline and Week 8 ]Glucose effectiveness as measured by insulin-modified IV glucose tolerance test using the MINMOD model.
- Change in HDL [ Time Frame: Baseline and Week 8 ]
- Change in Insulin [ Time Frame: Baseline and Week 8 ]fasting insulin (post - pre atenolol)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00925119
|United States, Maryland|
|University of Maryland|
|Baltimore, Maryland, United States, 21201|
|Principal Investigator:||Amber L. Beitelshees, PharmD, MPH||University of Maryland|