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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

July 21, 2005
November 12, 2013
May 2005
May 2011   (final data collection date for primary outcome measure)
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
Brachial artery flow mediated dilation (endothelial function)
Complete list of historical versions of study NCT00122447 on ClinicalTrials.gov Archive Site
AIM 1: Change in hsCRP (High Sensitivity C-reactive Peptide) Level [ Time Frame: 12 months of intervention ] [ Designated as safety issue: No ]
Inflammatory marker
  • Insulin sensitivity and beta cell function
  • Inflammatory markers
  • Markers of oxidative stress
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.

Not Provided
 
Cardiovascular Disease (CVD) Risk and Prevention in Early Glucose Intolerance
CVD Risk and Prevention in Early Glucose Intolerance

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Impaired Glucose Tolerance
  • Prediabetic State
  • Drug: Aspirin
    325 mg PO QD
    Other Name: Bayer aspirin
  • Drug: Alpha lipoic acid
    600 mg PO BID
  • Drug: Olmesartan
    40 mg PO QD
    Other Name: Benicar
  • 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

  • Active Comparator: Anti-inflammatory agent
    Aspirin (ASA)
    Intervention: Drug: Aspirin
  • Active Comparator: Angiotensin receptor blocker (ARB)
    Olmesartan (ARB)
    Intervention: Drug: Olmesartan
  • Active Comparator: Antioxidant
    Alpha lipoic acid (ALA)
    Intervention: Drug: Alpha lipoic acid
  • Placebo Comparator: Placebo
    Aspirin placebo once a day Olmesartan placebo once a day Alpha lipoic acid placebo twice a day
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
84
May 2011
May 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00122447
IRB00000749, UL1RR025008, Sankyo CS-866, 1K23DK070715-01A1
No
Dr. Mary Rhee, Emory University
Emory University
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Daiichi Sankyo Inc.
  • National Center for Research Resources (NCRR)
Principal Investigator: Mary K Rhee, MD, MS Emory University
Emory University
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP