Trial Outcomes & Findings for Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D) (NCT NCT00392678)
NCT ID: NCT00392678
Last Updated: 2019-04-08
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
277 participants
Primary outcome timeframe
14 week
Results posted on
2019-04-08
Participant Flow
3 private practices and 14 universities. First patient recruited February 2007; last patient end of study visit, May 2008
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.
Participant milestones
| Measure |
3 Gram
Salsalate 3.0 g daily, divided
|
3.5 Gram
Salsalate 3.5 g daily, divided
|
4 Gram
Salsalate 4.0 g daily, divided
|
Placebo
Matched by appearance to active drug
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
27
|
27
|
27
|
27
|
|
Overall Study
COMPLETED
|
27
|
26
|
25
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
2
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D)
Baseline characteristics by cohort
| Measure |
3 Gram
n=27 Participants
Salsalate 3.0 g daily, divided
|
3.5 Gram
n=27 Participants
Salsalate 3.5 g daily, divided
|
4 Gram
n=27 Participants
Salsalate 4.0 g daily, divided
|
Placebo
n=27 Participants
matched to active drug
|
Total
n=108 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
23 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
91 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Age, Continuous
|
55.4 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
56.7 years
STANDARD_DEVIATION 9.8 • n=7 Participants
|
55.0 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
55.9 years
STANDARD_DEVIATION 8.2 • n=4 Participants
|
56 years
STANDARD_DEVIATION 9 • n=21 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
45 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
63 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=5 Participants
|
27 participants
n=7 Participants
|
27 participants
n=5 Participants
|
27 participants
n=4 Participants
|
108 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 14 weekThe 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.
Outcome measures
| Measure |
3.0 g/d
n=27 Participants
Salsalate 3.0 g/d, divided
|
3.5 g/d
n=26 Participants
Salsalate 3.5 g/d, divided
|
4.0 g/d
n=25 Participants
Salsalate 4.0 g/d, divided
|
Placebo
n=26 Participants
Placebo matched to active drug
|
|---|---|---|---|---|
|
Change in HbA1c Baseline to End of Trial in TINSAL-T2D Stage 1
|
-0.36 % (units of HbA1c)
Interval -0.55 to -0.17
|
-0.34 % (units of HbA1c)
Interval -0.54 to -0.15
|
-0.49 % (units of HbA1c)
Interval -0.69 to -0.3
|
-0.01 % (units of HbA1c)
Interval -0.2 to 0.19
|
SECONDARY outcome
Timeframe: 14 weekChange from baseline to either 14 or 26 weeks, or last HbA1c measurement prior to rescue therapy
Outcome measures
| Measure |
3.0 g/d
n=26 Participants
Salsalate 3.0 g/d, divided
|
3.5 g/d
n=27 Participants
Salsalate 3.5 g/d, divided
|
4.0 g/d
n=26 Participants
Salsalate 4.0 g/d, divided
|
Placebo
n=25 Participants
Placebo matched to active drug
|
|---|---|---|---|---|
|
Change in HbA1c
|
0 % HbA1c
Interval -0.2 to 0.2
|
-0.4 % HbA1c
Interval -0.6 to -0.2
|
-0.3 % HbA1c
Interval -0.5 to -0.2
|
-0.5 % HbA1c
Interval -0.7 to -0.3
|
SECONDARY outcome
Timeframe: 14 weekOutcome measures
| Measure |
3.0 g/d
n=26 Participants
Salsalate 3.0 g/d, divided
|
3.5 g/d
n=27 Participants
Salsalate 3.5 g/d, divided
|
4.0 g/d
n=26 Participants
Salsalate 4.0 g/d, divided
|
Placebo
n=25 Participants
Placebo matched to active drug
|
|---|---|---|---|---|
|
Change From Baseline and Trends in Fasting Glucose Over Time
|
13 mg/dl
Interval 2.0 to 24.0
|
-19 mg/dl
Interval -30.0 to -8.0
|
-14 mg/dl
Interval -25.0 to -3.0
|
-15 mg/dl
Interval -26.0 to -4.0
|
SECONDARY outcome
Timeframe: 14 weekChange 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) LDL-C/HDL-C ratio not calculated
Outcome measures
| Measure |
3.0 g/d
n=26 Participants
Salsalate 3.0 g/d, divided
|
3.5 g/d
n=27 Participants
Salsalate 3.5 g/d, divided
|
4.0 g/d
n=26 Participants
Salsalate 4.0 g/d, divided
|
Placebo
n=27 Participants
Placebo matched to active drug
|
|---|---|---|---|---|
|
Change in Lipids
Cholesterol
|
0 mg/dl
Interval -7.0 to 8.0
|
8 mg/dl
Interval 1.0 to 16.0
|
-1 mg/dl
Interval -9.0 to 7.0
|
6 mg/dl
Interval -1.0 to 14.0
|
|
Change in Lipids
HDL
|
0 mg/dl
Interval -2.0 to 1.0
|
3 mg/dl
Interval 1.0 to 4.0
|
1 mg/dl
Interval -1.0 to 3.0
|
2 mg/dl
Interval 0.0 to 4.0
|
|
Change in Lipids
LDL
|
0 mg/dl
Interval -7.0 to 6.0
|
15 mg/dl
Interval 9.0 to 22.0
|
3 mg/dl
Interval -3.0 to 10.0
|
8 mg/dl
Interval 2.0 to 15.0
|
|
Change in Lipids
TG
|
15 mg/dl
Interval -6.0 to 36.0
|
-34 mg/dl
Interval -55.0 to -13.0
|
-22 mg/dl
Interval -43.0 to 0.0
|
-16 mg/dl
Interval -38.0 to 5.0
|
|
Change in Lipids
Total to HDL ratio
|
0 mg/dl
Interval -0.2 to 0.3
|
0.1 mg/dl
Interval -0.1 to 0.4
|
-0.1 mg/dl
Interval -0.3 to 0.2
|
0.2 mg/dl
Interval -0.1 to 0.4
|
SECONDARY outcome
Timeframe: Baseline, week 14HOMA-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.
Outcome measures
| Measure |
3.0 g/d
n=26 Participants
Salsalate 3.0 g/d, divided
|
3.5 g/d
n=27 Participants
Salsalate 3.5 g/d, divided
|
4.0 g/d
n=26 Participants
Salsalate 4.0 g/d, divided
|
Placebo
n=25 Participants
Placebo matched to active drug
|
|---|---|---|---|---|
|
Change From Baseline in 14-week Insulin, C-peptide, Homeostasis Model [HOMA] Index
|
-3.0 pmol/l
Interval -39.0 to 33.0
|
15 pmol/l
Interval 12.0 to 42.0
|
7.6 pmol/l
Interval -21.4 to 36.6
|
27 pmol/l
Interval -31.0 to 85.0
|
SECONDARY outcome
Timeframe: 14 weeksSee adverse event module for details. Safety and tolerability of salsalate compared to placebo as assessed by adverse events.
Outcome measures
| Measure |
3.0 g/d
n=27 Participants
Salsalate 3.0 g/d, divided
|
3.5 g/d
n=27 Participants
Salsalate 3.5 g/d, divided
|
4.0 g/d
n=27 Participants
Salsalate 4.0 g/d, divided
|
Placebo
n=27 Participants
Placebo matched to active drug
|
|---|---|---|---|---|
|
Safety and Tolerability
|
17 participants
|
16 participants
|
16 participants
|
14 participants
|
SECONDARY outcome
Timeframe: Baseline, week 14HOMA-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
Outcome measures
| Measure |
3.0 g/d
n=26 Participants
Salsalate 3.0 g/d, divided
|
3.5 g/d
n=27 Participants
Salsalate 3.5 g/d, divided
|
4.0 g/d
n=26 Participants
Salsalate 4.0 g/d, divided
|
Placebo
n=25 Participants
Placebo matched to active drug
|
|---|---|---|---|---|
|
Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index
|
0.10 C-peptide in nmol/l
Interval 0.0 to 0.2
|
-0.07 C-peptide in nmol/l
Interval -0.17 to 0.01
|
-0.03 C-peptide in nmol/l
Interval -0.13 to 0.1
|
0.03 C-peptide in nmol/l
Interval -0.07 to 0.13
|
Adverse Events
Salsalate 3.0 g/d
Serious events: 1 serious events
Other events: 27 other events
Deaths: 0 deaths
Salsalate 3.5 g/d
Serious events: 2 serious events
Other events: 27 other events
Deaths: 0 deaths
Salsalate 4.0 g/d
Serious events: 0 serious events
Other events: 27 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Salsalate 3.0 g/d
n=27 participants at risk
Active: Salsalate 3.0 g/d
|
Salsalate 3.5 g/d
n=27 participants at risk
Active: Salsalate 3.5 g/d
|
Salsalate 4.0 g/d
n=27 participants at risk
Active: Salsalate 4.0 g/d
|
Placebo
n=27 participants at risk
Identical Placebo
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Acute Cholecystitis
|
3.7%
1/27 • Number of events 1 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
Musculoskeletal and connective tissue disorders
Cervical Disc Herniation
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
3.7%
1/27 • Number of events 1 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
Cardiac disorders
Congestive Heart Failure with Diastolic Dysfunction
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
3.7%
1/27 • Number of events 1 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
Musculoskeletal and connective tissue disorders
Lumbar laminectomy
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
3.7%
1/27 • Number of events 1 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
Other adverse events
| Measure |
Salsalate 3.0 g/d
n=27 participants at risk
Active: Salsalate 3.0 g/d
|
Salsalate 3.5 g/d
n=27 participants at risk
Active: Salsalate 3.5 g/d
|
Salsalate 4.0 g/d
n=27 participants at risk
Active: Salsalate 4.0 g/d
|
Placebo
n=27 participants at risk
Identical Placebo
|
|---|---|---|---|---|
|
Cardiac disorders
Cardiorespiratory
|
14.8%
4/27 • Number of events 5 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
3.7%
1/27 • Number of events 1 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
11.1%
3/27 • Number of events 5 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
11.1%
3/27 • Number of events 7 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
Nervous system disorders
Neurologic
|
25.9%
7/27 • Number of events 9 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
37.0%
10/27 • Number of events 13 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
29.6%
8/27 • Number of events 8 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
25.9%
7/27 • Number of events 7 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
Gastrointestinal disorders
Gastrointestinal
|
40.7%
11/27 • Number of events 13 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
29.6%
8/27 • Number of events 8 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
29.6%
8/27 • Number of events 8 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
7.4%
2/27 • Number of events 3 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
29.6%
8/27 • Number of events 10 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
18.5%
5/27 • Number of events 5 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
11.1%
3/27 • Number of events 3 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
25.9%
7/27 • Number of events 9 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
General disorders
General
|
25.9%
7/27 • Number of events 8 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
14.8%
4/27 • Number of events 4 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
7.4%
2/27 • Number of events 2 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
14.8%
4/27 • Number of events 4 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
Endocrine disorders
Hypoglycemia
|
18.5%
5/27 • Number of events 63 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
22.2%
6/27 • Number of events 46 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
22.2%
6/27 • Number of events 7 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
7.4%
2/27 • Number of events 2 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
|
Endocrine disorders
Hyperglycemia
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
0.00%
0/27 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
7.4%
2/27 • Number of events 7 • Screening, 4 week placebo run in, 14 week treatment.
AE/SAE use standard FDA definition.
|
Additional Information
Allison B. Goldfine, MD co-investigator
Joslin Diabetes Center
Phone: 617-309-2643
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place