- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00925119
Examining Genetic Influence on Response to Beta-Blocker Medications in People With Type 2 Diabetes
Uncoupling Protein Polymorphisms and Cardiometabolic Responses to Beta-Blockers
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21201
- University of Maryland
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Atenolol
Participants will receive atenolol for 8 weeks.
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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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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Diastolic Function (Annular Tissue Velocity [Em])
Time Frame: 8 weeks
|
8 weeks
|
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Change in Free Fatty Acid Kinetics
Time Frame: Baseline and Week 8
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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
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Triglycerides
Time Frame: Baseline and Week 8
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(Post atenolol triglycerides - Pre atenolol triglycerides)
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Baseline and Week 8
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Change in Insulin Sensitivity
Time Frame: Baseline and Week 8
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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. |
Baseline and Week 8
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Change in Glucose Effectiveness
Time Frame: Baseline and Week 8
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Glucose effectiveness as measured by insulin-modified IV glucose tolerance test using the MINMOD model.
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Baseline and Week 8
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Change in HDL
Time Frame: Baseline and Week 8
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Baseline and Week 8
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Change in Insulin
Time Frame: Baseline and Week 8
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fasting insulin (post - pre atenolol)
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Baseline and Week 8
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Amber L. Beitelshees, PharmD, MPH, University of Maryland, Baltimore
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Sympatholytics
- Adrenergic beta-1 Receptor Antagonists
- Atenolol
Other Study ID Numbers
- HP-00040291
- K23HL091120 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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