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| ID | Type | Description | Link |
|---|---|---|---|
| K23HL091120 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atenolol | Experimental | Participants will receive atenolol for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atenolol | Drug | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Diastolic Function (Annular Tissue Velocity [Em]) | 8 weeks | |
| Change in Free Fatty Acid Kinetics | 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. | Baseline and Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Triglycerides | (Post atenolol triglycerides - Pre atenolol triglycerides) | Baseline and Week 8 |
| Change in Insulin Sensitivity | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amber L. Beitelshees, PharmD, MPH | University of Maryland, Baltimore | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland | Baltimore | Maryland | 21201 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Atenolol | Participants will receive atenolol for 8 weeks. Atenolol: 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Atenolol | Participants will receive atenolol for 8 weeks. Atenolol: 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Diastolic Function (Annular Tissue Velocity [Em]) | Data were not able to be collected from the echocardiography. | Posted | 8 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Atenolol | Participants will receive atenolol for 8 weeks. Atenolol: 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Amber Beitelshees | University of Maryland | 410-706-0118 | abeitels@medicine.umaryland.edu |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D001262 | Atenolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| Baseline and Week 8 |
| Change in Glucose Effectiveness | Glucose effectiveness as measured by insulin-modified IV glucose tolerance test using the MINMOD model. | Baseline and Week 8 |
| Change in HDL | Baseline and Week 8 |
| Change in Insulin | fasting insulin (post - pre atenolol) | Baseline and Week 8 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Primary | Change in Free Fatty Acid Kinetics | 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. | Modeling data not available in all subjects | Posted | Mean | Standard Deviation | mU/mL | Baseline and Week 8 |
|
|
|
| Secondary | Change in Triglycerides | (Post atenolol triglycerides - Pre atenolol triglycerides) | Data available in 17 subjects | Posted | Mean | Standard Deviation | mg/dL | Baseline and Week 8 |
|
|
|
| Secondary | Change in Insulin Sensitivity | 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. | Post and Pre atenolol data available in 17 subjects | Posted | Mean | Standard Deviation | arbitrary units | Baseline and Week 8 |
|
|
|
| Secondary | Change in Glucose Effectiveness | Glucose effectiveness as measured by insulin-modified IV glucose tolerance test using the MINMOD model. | Data could not be determined because assumptions for MINMOD model were not met. | Posted | Baseline and Week 8 |
|
|
| Secondary | Change in HDL | Posted | Mean | Standard Deviation | mg/dL | Baseline and Week 8 |
|
|
|
| Secondary | Change in Insulin | fasting insulin (post - pre atenolol) | Posted | Mean | Standard Deviation | mU/mL | Baseline and Week 8 |
|
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|
| 0 |
| 19 |
| 4 |
| 19 |
| Bradycardia | Cardiac disorders |
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| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |