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Trial record 7 of 11 for:    lipoic acid ms

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

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ClinicalTrials.gov Identifier: NCT00122447
Recruitment Status : Completed
First Posted : July 22, 2005
Results First Posted : June 20, 2012
Last Update Posted : December 5, 2013
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Daiichi Sankyo, Inc.
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Dr. Mary Rhee, Emory University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Impaired Glucose Tolerance
Prediabetic State
Interventions Drug: Aspirin
Drug: Alpha lipoic acid
Drug: Olmesartan
Drug: Placebo
Enrollment 84
Recruitment Details

266 subjects with IGT were contacted: 121 refused, 63 ineligible, 84 screened/enrolled.

Among the 84 enrolled subjects:

1 was withdrawn, 13 dropped out before randomization, 70 were randomized (17 alpha lipoic acid, 18 aspirin, 18 olmesartan, 17 placebo).

After randomization, 10 dropped out, and 3 were withdrawn.

Pre-assignment Details  
Arm/Group Title Aspirin (ASA) 325 mg PO Once Daily Olmesartan (ARB) 40 mg PO Once Daily Alpha Lipoic Acid (ALA) 600 mg PO Twice Daily Placebo
Hide Arm/Group Description Anti-inflammatory agent Angiotensin receptor blocker (ARB) Antioxidant Aspirin placebo PO once a day Olmesartan placebo PO once a day Alpha lipoic acid placebo PO twice a day
Period Title: Overall Study
Started 18 18 17 17
Completed 17 13 16 14
Not Completed 1 5 1 3
Arm/Group Title Aspirin (ASA) 325 mg PO Once Daily Olmesartan (ARB) 40 mg PO Once Daily Alpha Lipoic Acid (ALA) 600 mg PO Twice Daily Placebo Total
Hide Arm/Group Description Anti-inflammatory agent Angiotensin receptor blocker (ARB) Antioxidant Aspirin placebo PO once a day Olmesartan placebo PO once a day Alpha lipoic acid placebo PO twice a day Total of all reporting groups
Overall Number of Baseline Participants 18 18 17 17 70
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 18 participants 17 participants 17 participants 70 participants
51.4  (12.8) 55.2  (8.5) 52.4  (7.0) 51.3  (11.7) 52.6  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 18 participants 17 participants 17 participants 70 participants
Female
13
  72.2%
10
  55.6%
10
  58.8%
6
  35.3%
39
  55.7%
Male
5
  27.8%
8
  44.4%
7
  41.2%
11
  64.7%
31
  44.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 18 participants 17 participants 17 participants 70 participants
Black or African American 13 12 10 14 49
White 5 6 7 3 21
1.Primary Outcome
Title AIM 1: Change in Flow Mediated Dilation (FMD) (%)
Hide Description 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
Time Frame 12 months of intervention
Hide Outcome Measure Data
Hide Analysis Population Description
Based on the number of subjects who completed 12 months of intervention and testing
Arm/Group Title Aspirin (ASA) 325 mg PO Once Daily Olmesartan (ARB) 40 mg PO Once Daily Alpha Lipoic Acid (ALA) 600 mg PO Twice Daily Placebo
Hide Arm/Group Description:
Anti-inflammatory agent
Angiotensin receptor blocker (ARB)
Antioxidant
Aspirin placebo PO once a day Olmesartan placebo PO once a day Alpha lipoic acid placebo PO twice a day
Overall Number of Participants Analyzed 17 13 15 13
Mean (Standard Deviation)
Unit of Measure: percentage of arterial dilation change
-0.0012  (0.030) 0.018  (0.032) 0.014  (0.034) 0.0053  (0.030)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aspirin (ASA) 325 mg PO Once Daily, Placebo
Comments Null hypothesis: no difference between active treatment group compared to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.943
Comments Association between treatment arm, compared to placebo, on change in FMD from baseline to 12 months of intervention, adjusted for age, sex, race, and LDL-cholesterol.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.001
Confidence Interval (2-Sided) 95%
-0.025 to 0.023
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.012
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olmesartan (ARB) 40 mg PO Once Daily, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.280
Comments Association between treatment arm, compared to placebo, on change in FMD from baseline to 12 months of intervention, adjusted for age, sex, race, and LDL-cholesterol.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.014
Confidence Interval (2-Sided) 95%
-0.012 to 0.039
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.013
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Alpha Lipoic Acid (ALA) 600 mg PO Twice Daily, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.313
Comments Association between treatment arm, compared to placebo, on change in FMD from baseline to 12 months of intervention, adjusted for age, sex, race, and LDL-cholesterol.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.012
Confidence Interval (2-Sided) 95%
-0.012 to 0.037
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.012
Estimation Comments [Not Specified]
2.Secondary Outcome
Title AIM 1: Change in hsCRP (High Sensitivity C-reactive Peptide) Level
Hide Description Inflammatory marker
Time Frame 12 months of intervention
Hide Outcome Measure Data
Hide Analysis Population Description
Based on the number of subjects who completed 12 months of intervention and testing
Arm/Group Title Aspirin (ASA) 325 mg PO Once Daily Olmesartan (ARB) 40 mg PO Once Daily Alpha Lipoic Acid (ALA) 600 mg PO Twice Daily Placebo
Hide Arm/Group Description:
Anti-inflammatory agent
Angiotensin receptor blocker (ARB)
Antioxidant
Aspirin placebo PO once a day Olmesartan placebo PO once a day Alpha lipoic acid placebo PO twice a day
Overall Number of Participants Analyzed 11 11 11 10
Mean (Standard Error)
Unit of Measure: mg/L
-1.27  (0.86) -2.34  (1.1) 0.23  (0.70) 0.32  (0.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aspirin (ASA) 325 mg PO Once Daily, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.449
Comments Association between treatment arm, compared to placebo, on change in hsCRP from baseline to 12 months of intervention, adjusted for age, sex, and race.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.941
Confidence Interval (2-Sided) 95%
-3.435 to 1.552
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.229
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olmesartan (ARB) 40 mg PO Once Daily, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments Association between treatment arm, compared to placebo, on change in hsCRP from baseline to 12 months of intervention, adjusted for age, sex, and race.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -2.677
Confidence Interval (2-Sided) 95%
-5.133 to -0.221
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.211
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Alpha Lipoic Acid (ALA) 600 mg PO Twice Daily, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.943
Comments Association between treatment arm, compared to placebo, on change in hsCRP from baseline to 12 months of intervention, adjusted for age, sex, and race.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.088
Confidence Interval (2-Sided) 95%
-2.367 to 2.542
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.210
Estimation Comments [Not Specified]
3.Other Pre-specified Outcome
Title AIM 2: Difference in FMD (Measure of Endothelial Function)
Hide Description

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.

Time Frame Cross-sectional
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Normal Glucose Tolerance (NGT) Impaired Glucose Tolerance (IGT) Diabetes
Hide Arm/Group Description:
Normal fasting glucose (<100 mg/dl) and normal 2-hr glucose level (<140 mg/dl) after 75g OGTT

After 75g OGTT:

Fasting glucose <126 mg/dl and 2-hr glucose level 140-199 mg/dl

After 75g OGTT:

Fasting glucose >=126 mg/dl and 2-hr glucose level >=200 mg/dl

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 12 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Aspirin Olmesartan Alpha Lipoic Acid Placebo Enrolled, But Not Yet Randomized
Hide Arm/Group Description Anti-inflammatory agent Angiotensin receptor blocker (ARB) Antioxidant Aspirin placebo once a day Olmesartan placebo once a day Alpha lipoic acid placebo twice a day Enrolled into study, but not yet randomized to study medication
All-Cause Mortality
Aspirin Olmesartan Alpha Lipoic Acid Placebo Enrolled, But Not Yet Randomized
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Aspirin Olmesartan Alpha Lipoic Acid Placebo Enrolled, But Not Yet Randomized
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      0/18 (0.00%)      0/17 (0.00%)      0/17 (0.00%)      1/14 (7.14%)    
Gastrointestinal disorders           
Cancer [1]  0/18 (0.00%)  0 0/18 (0.00%)  0 0/17 (0.00%)  0 0/17 (0.00%)  0 1/14 (7.14%)  1
[1]
Pt was diagnosed with pancreatic cancer soon after enrollment, but before randomization to intervention group.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aspirin Olmesartan Alpha Lipoic Acid Placebo Enrolled, But Not Yet Randomized
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      1/18 (5.56%)      0/17 (0.00%)      0/17 (0.00%)      0/14 (0.00%)    
Cardiac disorders           
Reaction to nitroglycerin during FMD test [1]  0/18 (0.00%)  0 1/18 (5.56%)  1 0/17 (0.00%)  0 0/17 (0.00%)  0 0/14 (0.00%)  0
[1]
During baseline FMD testing, prior to actually starting study medication, a vasavagal response to NTG was developed.
Not fully powered due to under-enrollment and high drop-out rate. Higher than anticipated precision error of FMD measures. Possible Hawthorne effect with lifestyle changes. Short treatment period relative to long-term CVD risk in prediabetes.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Mary Rhee, M.D.
Organization: Emory University School of Medicine
Phone: 404-778-1660
Responsible Party: Dr. Mary Rhee, Emory University
ClinicalTrials.gov Identifier: NCT00122447     History of Changes
Other Study ID Numbers: IRB00000749
UL1RR025008 ( U.S. NIH Grant/Contract )
Sankyo CS-866 ( Other Identifier: Daiichi Sankyo )
1K23DK070715-01A1 ( U.S. NIH Grant/Contract )
First Submitted: July 21, 2005
First Posted: July 22, 2005
Results First Submitted: May 18, 2012
Results First Posted: June 20, 2012
Last Update Posted: December 5, 2013