Cardiovascular Disease (CVD) Risk and Prevention in Early Glucose Intolerance

This study has been completed.
Sponsor:
Collaborators:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Dr. Mary Rhee, Emory University
ClinicalTrials.gov Identifier:
NCT00122447
First received: July 21, 2005
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to determine whether cardiovascular disease (CVD) risk markers, β-cell function, and insulin sensitivity can be improved by targeting mechanisms of both diabetes and CVD - using an antioxidant, an angiotensin II receptor blocker (ARB), or an anti-inflammatory agent - in patients with impaired glucose tolerance (IGT) in a randomized, controlled trial.


Condition Intervention
Impaired Glucose Tolerance
Prediabetic State
Drug: Aspirin
Drug: Alpha lipoic acid
Drug: Olmesartan
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: CVD Risk and Prevention in Early Glucose Intolerance

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • AIM 1: Change in Flow Mediated Dilation (FMD) (%) [ Time Frame: 12 months of intervention ] [ Designated as safety issue: No ]
    Surrogate measure of endothelial function defined as the percent change in dilation of the brachial artery after cuff compression of arm compared to before cuff compression


Secondary Outcome Measures:
  • AIM 1: Change in hsCRP (High Sensitivity C-reactive Peptide) Level [ Time Frame: 12 months of intervention ] [ Designated as safety issue: No ]
    Inflammatory marker


Other Outcome Measures:
  • AIM 2: Difference in FMD (Measure of Endothelial Function) [ Time Frame: Cross-sectional ] [ Designated as safety issue: No ]

    Comparison of FMD (measure of endothelial function) between NGT, IGT and diabetes at baseline. FMD is a surrogate measure of endothelial function defined as the percent change in dilation of the brachial artery after cuff compression of arm compared to before cuff compression.

    No analysis was conducted due to under-recruitment.



Enrollment: 84
Study Start Date: May 2005
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Anti-inflammatory agent
Aspirin (ASA)
Drug: Aspirin
325 mg PO QD
Other Name: Bayer aspirin
Active Comparator: Angiotensin receptor blocker (ARB)
Olmesartan (ARB)
Drug: Olmesartan
40 mg PO QD
Other Name: Benicar
Active Comparator: Antioxidant
Alpha lipoic acid (ALA)
Drug: Alpha lipoic acid
600 mg PO BID
Placebo Comparator: Placebo
Aspirin placebo once a day Olmesartan placebo once a day Alpha lipoic acid placebo twice a day
Drug: Placebo

Identical placebo for each active comparator:

placebo aspirin 325 mg PO QD; placebo for alpha lipoic acid 600 mg PO BID; placebo for olmesartan 40 mg PO QD


  Hide Detailed Description

Detailed Description:

Diabetes is a common, major health problem in the United States, and it significantly increases the risk of developing heart disease, which is the leading cause of death. Research studies have shown that the risk of heart disease is increased, even in the "pre-diabetes" or impaired glucose tolerance (IGT) stage, before the onset of true diabetes. While many studies have shown that aggressive management of diabetes lowers the risk of heart disease, at the present time, it is not known how best to treat patients with impaired glucose tolerance (pre-diabetes) to prevent the development of heart disease. It is also not known where in the range of blood sugar levels risk begins to increase. The purpose of this study is to determine:

  • whether medications, which target pathways involved in the development of heart disease, can decrease the risk of heart disease in individuals with impaired glucose tolerance; and
  • whether a "high" blood sugar level measured one hour after drinking a standard high-sugar drink is associated with an increased risk of heart disease even in individuals who have no evidence of diabetes or pre-diabetes.

The purpose of Aim 1 of this study is to determine whether medications, which target pathways involved in the development of heart disease, can decrease the risk of heart disease in individuals with impaired glucose tolerance. One hundred-twenty volunteers with impaired glucose tolerance and 30 volunteers with normal glucose tolerance (normal blood sugars after ingesting a standard high-sugar drink) will be recruited from the "Screening for Impaired Glucose Tolerance" (SIGT) study. The 30 volunteers with normal glucose tolerance will not take any study medication, but will undergo medical testing to determine their risk of heart disease at the beginning of the study, after which their participation in the study will be complete. The 120 volunteers with impaired glucose tolerance will be randomly assigned to one of four medications to be taken over a one-year period:

  • alpha lipoic acid (an antioxidant, dietary supplement);
  • olmesartan (a drug used to treat high blood pressure);
  • aspirin (an anti-inflammatory drug); and
  • placebo (an inactive, "dummy" pill).

Subjects with impaired glucose tolerance will undergo medical testing to determine their risk of heart disease at the beginning of the study (before beginning study medications), after 3 months of intervention, and again at the end of the study (12 months after enrollment). Test results will be compared between the subjects taking each of the active medications and those taking placebo, to determine if the medications lead to a significant reduction in the risk for the development of heart disease. The medical tests used in this study are currently used in medical practice, and include blood and urine specimens, ultrasound testing of the artery at the arm, and an insulin sensitivity test (test of how effectively the body uses sugar). All visits and tests will be conducted in the General Clinical Research Centers of Emory University Hospital and Grady Memorial Hospital.

The purpose of Aim 2 of this study is to determine whether a "high" blood sugar level measured one hour after drinking a standard high-sugar drink (1-hour blood sugar level) is associated with an increased risk of heart disease even in individuals who have no evidence of diabetes or pre-diabetes. Seventy-five volunteers with normal glucose tolerance (normal blood sugars after ingesting a standard high-sugar drink) will be recruited from the SIGT study, as well as 15 subjects with impaired glucose tolerance and 15 with diabetes. The subjects with normal glucose tolerance will be grouped into those with "low", "middle", and "high" 1-hour blood sugar levels. All subjects will undergo medical testing (as in Aim 1 above) to determine their risk of heart disease. Test results of subjects with "low", "middle", and "high" 1-hour blood sugar levels will be compared against one another, as well as against those of subjects with IGT and diabetes. If subjects with normal glucose tolerance but "high" 1-hour blood sugar levels are found to have increased risk for heart disease compared to those with "low" 1-hour blood sugar levels, then the 1-hour blood sugar levels may provide important information regarding an increased risk of heart disease even in individuals with normal glucose tolerance but "high" 1-hour blood sugar levels - a population which otherwise would not be identified with the current standard tests used for the diagnosis of diabetes and pre-diabetes.

Over 40 million Americans have pre-diabetes (impaired glucose tolerance), which is associated with an increased risk of the development of both diabetes and heart disease. Findings from these studies will provide important insights into the pathways that lead to the development of heart disease related to pre-diabetes, prevention of heart disease in the pre-diabetic population, and identification of individuals at high risk for heart disease earlier in their natural history - even before the onset of pre-diabetes.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Impaired glucose tolerance

Exclusion Criteria:

  • Diagnosis of diabetes
  • Taking an ACE inhibitor (ACE-I), angiotensin II receptor blocker (ARB), or aspirin
  • Have systolic blood pressure >140 mm Hg
  • Have a chronic inflammatory disorder (i.e. rheumatoid arthritis, inflammatory bowel disease, sinusitis)
  • Vascular disease (cardiac, peripheral, cerebral)
  • Renal insufficiency or hepatic abnormalities
  • Gastrointestinal bleeding (defined as gastric or duodenal ulcer, hematemesis, and/or blood in the stool) or significant other upper gastrointestinal problems (i.e. gastritis) within the previous 6 months
  • Anemia or a history of bleeding disorder
  • Have a history of ARB or aspirin allergy
  • Have the syndrome of asthma, rhinitis, and nasal polyps
  • Have other medical problems which would preclude taking potential study medications for 12 months
  • Are pregnant or have a positive pregnancy test
  • Are breast feeding
  • Are unable or unwilling to tolerate having one catheter in each arm for 4 hours
  • Have health status such that the envisioned blood sampling would confer a physiologic risk
  • Have other physical, social, or behavioral problems which would decrease the likelihood that they would remain in the study for 12 months
  • Do not appear capable of giving informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00122447

Locations
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
Grady Health System
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
Daiichi Sankyo Inc.
Investigators
Principal Investigator: Mary K Rhee, MD, MS Emory University
  More Information

No publications provided

Responsible Party: Dr. Mary Rhee, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT00122447     History of Changes
Other Study ID Numbers: IRB00000749, UL1RR025008, Sankyo CS-866, 1K23DK070715-01A1
Study First Received: July 21, 2005
Results First Received: May 18, 2012
Last Updated: November 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Prediabetic state
Cardiovascular disease
Diabetes
Glucose intolerance

Additional relevant MeSH terms:
Cardiovascular Diseases
Glucose Intolerance
Prediabetic State
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Aspirin
Anti-Inflammatory Agents
Olmesartan medoxomil
Thioctic Acid
Olmesartan
Angiotensin Receptor Antagonists
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014