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Salsalate Therapy to Reduce Insulin Resistance and Cardiovascular Risk

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ClinicalTrials.gov Identifier: NCT00330733
Recruitment Status : Completed
First Posted : May 29, 2006
Results First Posted : April 22, 2014
Last Update Posted : April 22, 2014
Sponsor:
Collaborator:
Joslin Diabetes Center
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Atherosclerosis
Cardiovascular Disease
Inflammation
Insulin Resistance
Noninsulin-dependent Diabetes Mellitus
Interventions Drug: Salsalate
Drug: Placebo
Enrollment 71
Recruitment Details Participants were veterans aged 21–75 years with impaired fasting glucose (i.e. ≥5.6 but <7 mmol/l) or impaired glucose tolerance (2 h glucose values ≥7.8 but <11.1 mmol/l) during a standard 2 h 75 g OGTT. Study participants were recruited from clinics and hospitals throughout the Phoenix and Boston VA Health Care systems.
Pre-assignment Details After enrolment there were 1 week screening, 3 week single-masked placebo run-in (to assess compliance) and 12 week randomised, double-masked treatment periods, with participants randomised 1:1 to receive salsalate or placebo. 78 individuals entered the run-in phase.
Arm/Group Title Arm 1 Arm 2
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Matching placebo

Placebo: Matching placebo

Seventy-eight individuals entered the placebo run-in phase. Of these, 71 were randomised and 70 returned to receive study medication

Salsalate

Salsalate: Salsalate therapy

Period Title: Overall Study
Started 37 34
Received Study Medication 36 34
Completed 30 29
Not Completed 7 5
Arm/Group Title Arm 1 Arm 2 Total
Hide Arm/Group Description

Matching placebo

Placebo: Matching placebo

Salsalate

Salsalate: Salsalate therapy, double-masked

Total of all reporting groups
Overall Number of Baseline Participants 36 34 70
Hide Baseline Analysis Population Description
Seventy-eight individuals entered the placebo run-in phase. Of these, 71 were randomised and 70 returned to receive study medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 34 participants 70 participants
57  (9) 60  (6) 58  (8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 34 participants 70 participants
Female
1
   2.8%
2
   5.9%
3
   4.3%
Male
35
  97.2%
32
  94.1%
67
  95.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 36 participants 34 participants 70 participants
36 34 70
Euglycemic clamps   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/ kg . min
Number Analyzed 36 participants 34 participants 70 participants
4.08  (1.46) 3.8  (1.0) 3.93  (1.27)
[1]
Measure Description: glucose disposal
Oral Glucose Tolerance Test   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/dl. min
Number Analyzed 36 participants 34 participants 70 participants
167  (21) 165  (17) 166  (19)
[1]
Measure Description: Area Under the Curve Measurement
Fasting glucose  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 36 participants 34 participants 70 participants
105  (12) 103  (10) 104  (11)
1.Primary Outcome
Title Change in Systemic Glucose Disposal- Glucose Infusion Rates
Hide Description Participants were admitted to the Clinical Research Units at 06:00–08:00 hours after an overnight fast. Euglycaemic–hyperinsulinaemic clamps were conducted at baseline and at the end of the study. Because salsalate therapy appears to decrease insulin clearance leading to higher circulating insulin levels during the clamp, we reduced the infusion rate of insulin in the active treatment arm by 20% (from 100 to 80 mUm−2 min−1) at the study end. Insulin solutions were prepared by the site pharmacist so that study staff remained blinded to drug assignment. Whole-body insulin sensitivity was estimated from glucose infusion rate (GIR) during last 30 min of insulin infusions.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
analysis was performed on all participants with available baseline and final clamp studies
Arm/Group Title Arm 1 Arm 2
Hide Arm/Group Description:

Matching placebo

Placebo: Matching placebo

Salsalate

Salsalate: Salsalate therapy

Overall Number of Participants Analyzed 29 29
Median (95% Confidence Interval)
Unit of Measure: percent change from baseline
1
(-39 to 56)
6
(-20 to 61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm 1, Arm 2
Comments Paired comparisons (follow-up vs baseline) and unpaired group comparisons were performed by Student’s t tests or Wilcoxon signed rank tests.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Glucose Area Under the Curve in These Subjects
Hide Description [Not Specified]
Time Frame 3 months
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Plasma Levels of a Variety of Inflammatory Proteins
Hide Description [Not Specified]
Time Frame 8 and 12 weeks
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Parameters of Cardiovascular Disease Risk, Including Glucose, Triglycerides, HDL and Blood Pressure
Hide Description [Not Specified]
Time Frame 8 and 12 weeks
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Endothelial Dysfunction
Hide Description [Not Specified]
Time Frame 8 and 12 weeks
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm 1 Arm 2
Hide Arm/Group Description

Matching placebo

Placebo: Matching placebo The frequency of tinnitus was relatively low (n=4 for salsalate, n= 2 for placebo), only one instance was graded > mild. Gastrointestinal complaints did not differ between groups (n= 8 for salsalate, n=5 for placebo). No hypoglycaemia occurred.

Salsalate

Salsalate: Salsalate therapy The frequency of tinnitus was relatively low (n=4 for salsalate, n= 2 for placebo), only one instance was graded > mild. Gastrointestinal complaints did not differ between groups (n= 8 for salsalate, n=5 for placebo). No hypoglycaemia occurred.

All-Cause Mortality
Arm 1 Arm 2
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm 1 Arm 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/36 (0.00%)      0/34 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm 1 Arm 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/36 (19.44%)      12/34 (35.29%)    
Ear and labyrinth disorders     
tinnitus  [1]  2/36 (5.56%)  2 4/34 (11.76%)  4
Gastrointestinal disorders     
nausea   5/36 (13.89%)  5 8/34 (23.53%)  8
Indicates events were collected by systematic assessment
[1]
The frequency of tinnitus was relatively low (n=4 for salsalate, n= 2 for placebo), only one instance was graded > mild
Since we did not measure endogenous glucose production and lipolysis, the effects on hepatic glucose and lipid metabolism deserve further study. Sufficient numbers of women were not included, with which to confidently extend these results to women
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Peter Reaven
Organization: Phoenix VA Health Care System
Phone: 602 277 5551 ext 5817
EMail: Peter.Reaven@va.gov
Layout table for additonal information
Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
ClinicalTrials.gov Identifier: NCT00330733     History of Changes
Other Study ID Numbers: CLIN-011-05F
First Submitted: May 26, 2006
First Posted: May 29, 2006
Results First Submitted: December 18, 2013
Results First Posted: April 22, 2014
Last Update Posted: April 22, 2014