Examining Genetic Influence on Response to Beta-Blocker Medications in People With Type 2 Diabetes

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by National Heart, Lung, and Blood Institute (NHLBI).
Recruitment status was  Recruiting
Sponsor:
Collaborator:
University of Maryland
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00925119
First received: June 17, 2009
Last updated: September 10, 2010
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Atenolol
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Uncoupling Protein Polymorphisms and Cardiometabolic Responses to Beta-Blockers

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Change in diastolic function (annular tissue velocity [Em]) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in free fatty acid kinetics [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in insulin sensitivity, glucose effectiveness, glucose, insulin, high-density lipoprotein (HDL), or triglycerides [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: December 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atenolol
Participants will receive atenolol for 8 weeks.
Drug: 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

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

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes for more than 1 year before study entry

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00925119

Contacts
Contact: Amber L Beitelshees, PharmD, MPH 410-706-0118 abeitels@medicine.umaryland.edu

Locations
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Sub-Investigator: Alan Shuldiner, MD         
Sub-Investigator: Richard Horenstein, MD         
Sub-Investigator: Stephen Liggett, MD         
Sub-Investigator: John C. McLenithan, PhD         
Sub-Investigator: John Gottdiener, MD         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Amber L. Beitelshees, PharmD, MPH University of Maryland, Baltimore County
  More Information

No publications provided

Responsible Party: Amber L. Beitelshees, PharmD, MPH, University of Maryland School of Medicine
ClinicalTrials.gov Identifier: NCT00925119     History of Changes
Other Study ID Numbers: 660, K23 HL091120
Study First Received: June 17, 2009
Last Updated: September 10, 2010
Health Authority: United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Diabetes
Atenolol
Genetic

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Adrenergic beta-Antagonists
Atenolol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists

ClinicalTrials.gov processed this record on September 30, 2014