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Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D) (TINSAL-T2D)

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ClinicalTrials.gov Identifier: NCT00392678
Recruitment Status : Completed
First Posted : October 26, 2006
Results First Posted : July 26, 2013
Last Update Posted : December 11, 2017
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Joslin Diabetes Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Type 2 Diabetes
Interventions Drug: Salsalate
Drug: Placebo
Enrollment 277
Recruitment Details 3 private practices and 14 universities. First patient recruited February 2007; last patient end of study visit, May 2008
Pre-assignment Details Screening, followed by 4-week single mask placebo lead-in. 277 participants signed screening consent. Some participants were ineligible, some withdrew consent, and some had treatment side effects during placebo lead-in.
Arm/Group Title Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d Placebo
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified] [Not Specified]
Period Title: Overall Study
Started 27 27 27 27
Completed 27 26 25 26
Not Completed 0 1 2 1
Arm/Group Title Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d Placebo Total
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 27 27 27 27 108
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 27 participants 27 participants 27 participants 108 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
23
  85.2%
22
  81.5%
24
  88.9%
22
  81.5%
91
  84.3%
>=65 years
4
  14.8%
5
  18.5%
3
  11.1%
5
  18.5%
17
  15.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants 27 participants 27 participants 27 participants 108 participants
55.4  (9.4) 56.7  (9.8) 55.0  (10.2) 55.9  (8.2) 56  (9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 27 participants 27 participants 27 participants 108 participants
Female
13
  48.1%
9
  33.3%
11
  40.7%
12
  44.4%
45
  41.7%
Male
14
  51.9%
18
  66.7%
16
  59.3%
15
  55.6%
63
  58.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 27 participants 27 participants 27 participants 27 participants 108 participants
27 27 27 27 108
1.Primary Outcome
Title The Primary Outcome for the TINSAL-T2D Study is Change in HbA1c Level From Baseline to Week 14 (Stage 1) in the Intent-to-treat (ITT) Population With Last Observation Carried Forward.
Hide Description [Not Specified]
Time Frame 14 week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d Placebo
Hide Arm/Group Description:
Salsalate 3.0 g/d, divided
Salsalate 3.5 g/d, divided
Salsalate 4.0 g/d, divided
Placebo
Overall Number of Participants Analyzed 27 26 25 26
Mean (95% Confidence Interval)
Unit of Measure: % (units of HbA1c)
-0.36
(-0.55 to -0.17)
-0.34
(-0.54 to -0.15)
-0.49
(-0.69 to -0.30)
-0.01
(-0.20 to 0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Salsalate 3.0 g/d, Salsalate 3.5 g/d, Salsalate 4.0 g/d, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Either 14 or 26 Weeks, or Last HbA1c Measurement Prior to Rescue Therapy
Hide Description see primary outcome
Time Frame 14 week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d
Hide Arm/Group Description:
Placebo
Salsalate 3.0 g/d, divided
Salsalate 3.5 g/d, divided
Salsalate 4.0 g/d, divided
Overall Number of Participants Analyzed 26 27 26 25
Mean (95% Confidence Interval)
Unit of Measure: % HbA1c
0
(-0.2 to 0.2)
-0.4
(-0.6 to -0.2)
-0.3
(-0.5 to -0.2)
-0.5
(-0.7 to -0.3)
3.Secondary Outcome
Title Change From Baseline and Trends in Fasting Glucose Over Time
Hide Description [Not Specified]
Time Frame 14 week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d
Hide Arm/Group Description:
Placebo
Salsalate 3.0 g/d, divided
Salsalate 3.5 g/d, divided
Salsalate 4.0 g/d, divided
Overall Number of Participants Analyzed 26 27 26 25
Mean (95% Confidence Interval)
Unit of Measure: mg/dl
13
(2 to 24)
-19
(-30 to -8)
-14
(-25 to -3)
-15
(-26 to -4)
4.Secondary Outcome
Title Response Rates for Reduction in Fasting Glucose of ≥20 mg/dl, a Reduction in HbA1c of ≥0.5%, and a Reduction in HbA1c of ≥0.8%
Hide Description This was an aim proposed for the longer duration study and is reported under TINSAL-T2D stage 2.
Time Frame 14-26 week
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Change in Lipids (Low-density Lipoprotein Cholesterol [LDL-C], Non-high-density Lipoprotein Cholesterol [Non-HDL-C], Triglycerides [TG], Total Cholesterol [TC], High-density Lipoprotein Cholesterol [HDL C], TC/HDL-C Ratio, and LDL-C/HDL-C Ratio)
Hide Description LDL-C/HDL-C ratio not calculated
Time Frame 14 week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d
Hide Arm/Group Description:
Placebo
Salsalate 3.0 g/d, divided
Salsalate 3.5 g/d, divided
Salsalate 4.0 g/d, divided
Overall Number of Participants Analyzed 26 27 26 27
Mean (95% Confidence Interval)
Unit of Measure: mg/dl
Cholesterol
0
(-7 to 8)
8
(1 to 16)
-1
(-9 to 7)
6
(-1 to 14)
HDL
0
(-2 to 1)
3
(1 to 4)
1
(-1 to 3)
2
(0 to 4)
LDL
0
(-7 to 6)
15
(9 to 22)
3
(-3 to 10)
8
(2 to 15)
TG
15
(-6 to 36)
-34
(-55 to -13)
-22
(-43 to 0)
-16
(-38 to 5)
Total to HDL ratio
0
(-0.2 to 0.3)
0.1
(-0.1 to 0.4)
-0.1
(-0.3 to 0.2)
0.2
(-0.1 to 0.4)
6.Secondary Outcome
Title Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index
Hide Description HOMA-IR was not calcuated due to potential confounding effect of salicylates to inhibit insulin clearance. Change in insulin from Baseline to Week 14 in data table below.
Time Frame Baseline, week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d
Hide Arm/Group Description:
Placebo
Salsalate 3.0 g/d, divided
Salsalate 3.5 g/d, divided
Salsalate 4.0 g/d, divided
Overall Number of Participants Analyzed 26 27 26 25
Median (Inter-Quartile Range)
Unit of Measure: pmol/l
-3.0 [1] 
(36 to NA)
15 [1] 
(27 to NA)
7.6 [1] 
(29 to NA)
27 [1] 
(58 to NA)
[1]
NA IQR provided as Q3-Q1
7.Secondary Outcome
Title Response Rates for Exceeding Hyperglycemic Targets Between Active and Placebo Treated Groups
Hide Description Please see adverse events module for hyperglycemia.
Time Frame 14 week
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Need for Rescue Therapy
Hide Description This aim was proposed for the TINSAL-T2D stage 2 trial and is separately reported.
Time Frame 14 weeks
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Need for Discontinuation of Study Medication
Hide Description This aim was proposed for the TINSAL-T2D stage 2 trial and is separately reported.
Time Frame 14 week
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Response Rates in Patients Initially Treated With Lifestyle Modification, Insulin Secretagogue, Metformin or Combination Therapy
Hide Description This aim was proposed for the TINSAL-T2D stage 2 trial and is separately reported.
Time Frame 14-26 week
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Response Rates for a Reduction in HbA1c for Obese vs Non-obese Participants
Hide Description This aim was proposed for the TINSAL-T2D stage 2 trial and is separately reported.
Time Frame 14-26 week
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Safety and Tolerability of Salsalate Compared to Placebo as Assessed by Adverse Events.
Hide Description See adverse event module for details.
Time Frame 14 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d Placebo
Hide Arm/Group Description:
Salsalate 3.0 g/d, divided
Salsalate 3.5 g/d, divided
Salsalate 4.0 g/d, divided
Placebo
Overall Number of Participants Analyzed 27 27 27 27
Measure Type: Number
Unit of Measure: participants
17 16 16 14
13.Secondary Outcome
Title Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index
Hide Description HOMA-IR was not calcuated due to potential confounding effect of salicylates to inhibit insulin clearance. Change in C-peptide from Baseline to Week 14 is in the data table below
Time Frame Baseline, week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d
Hide Arm/Group Description:
Placebo
Salsalate 3.0 g/d, divided
Salsalate 3.5 g/d, divided
Salsalate 4.0 g/d, divided
Overall Number of Participants Analyzed 26 27 26 25
Mean (95% Confidence Interval)
Unit of Measure: C-peptide in nmol/l
0.10
(0 to 0.2)
-0.07
(-0.17 to 0.01)
-0.03
(-0.13 to 0.10)
0.03
(-0.07 to 0.13)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d Placebo
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified] [Not Specified]
All-Cause Mortality
Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/27 (3.70%)      2/27 (7.41%)      0/27 (0.00%)      1/27 (3.70%)    
Cardiac disorders         
Congestive Heart Failure with Diastolic Dysfunction [1]  0/27 (0.00%)  0 1/27 (3.70%)  1 0/27 (0.00%)  0 0/27 (0.00%)  0
Gastrointestinal disorders         
Acute Cholecystitis [2]  1/27 (3.70%)  1 0/27 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Cervical Disc Herniation [3]  0/27 (0.00%)  0 1/27 (3.70%)  1 0/27 (0.00%)  0 0/27 (0.00%)  0
Lumbar laminectomy [4]  0/27 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 1/27 (3.70%)  1
[1]
Hospitalization for Congestive Heart Failure with Diastolic Dysfunction.
[2]
Hospitalization for Acute Cholecystitis, laparoscopic cholecystectomy performed.
[3]
1. Hospitalization for Cervical Disc Herniation.
[4]
Hospitalization for Lumbar laminectomy.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Salsalate 3.0 g/d Salsalate 3.5 g/d Salsalate 4.0 g/d Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/27 (100.00%)      27/27 (100.00%)      27/27 (100.00%)      25/27 (92.59%)    
Cardiac disorders         
Cardiorespiratory  [1]  4/27 (14.81%)  5 1/27 (3.70%)  1 3/27 (11.11%)  5 3/27 (11.11%)  7
Endocrine disorders         
Hypoglycemia   5/27 (18.52%)  63 6/27 (22.22%)  46 6/27 (22.22%)  7 2/27 (7.41%)  2
Hyperglycemia   0/27 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 2/27 (7.41%)  7
Gastrointestinal disorders         
Gastrointestinal  [2]  11/27 (40.74%)  13 8/27 (29.63%)  8 8/27 (29.63%)  8 2/27 (7.41%)  3
General disorders         
General  [3]  7/27 (25.93%)  8 4/27 (14.81%)  4 2/27 (7.41%)  2 4/27 (14.81%)  4
Musculoskeletal and connective tissue disorders         
Musculoskeletal  [4]  8/27 (29.63%)  10 5/27 (18.52%)  5 3/27 (11.11%)  3 7/27 (25.93%)  9
Nervous system disorders         
Neurologic  [5]  7/27 (25.93%)  9 10/27 (37.04%)  13 8/27 (29.63%)  8 7/27 (25.93%)  7
Indicates events were collected by systematic assessment
[1]
Includes palpitations, chest pain or discomfort, and swelling of legs or feet
[2]
incudes heartburn, nausea, vomiting, diarrhea
[3]
Includes fainting, dizziness, weakness or fatigue.
[4]
Includes stiffness, muscle or joint pain, arthritis, backache.
[5]
Includes blurry vision, dots or flashes in vision, tinnitus, and numbness or tingling.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Allison B. Goldfine, MD co-investigator
Organization: Joslin Diabetes Center
Phone: 617-309-2643
Responsible Party: Joslin Diabetes Center
ClinicalTrials.gov Identifier: NCT00392678     History of Changes
Other Study ID Numbers: CHS 06-20, NIH U01 DK74556
U01DK074556 ( U.S. NIH Grant/Contract )
First Submitted: October 25, 2006
First Posted: October 26, 2006
Results First Submitted: February 20, 2013
Results First Posted: July 26, 2013
Last Update Posted: December 11, 2017