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

Primary Purpose

Type 2 Diabetes

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Salsalate

Placebo

About this trial

This is an interventional treatment trial for Type 2 Diabetes focused on measuring Type 2 Diabetes, Inflammation, Obesity, Metabolic Syndrome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Type 2 diabetes on diet and exercise therapy or monotherapy with metformin, insulin secretagogue, or alpha-glucosidase inhibitors, or a low-dose combination of these at ≤ 50% maximal dose (see Appendix). Dosing is stable for 8 weeks prior to randomization.
FPG ≤ 225 mg/dL and HbA1c>7% and ≤9.5% at screening
Age ≥18 and <75
Women of childbearing potential agree to use an appropriate contraceptive method (hormonal, IUD, or diaphragm)

Exclusion Criteria:

Type 1 diabetes and/or history of ketoacidosis determined by medical history
History of severe diabetic neuropathy including autonomic neuropathy, gastroparesis or lower limb ulceration or amputation
History of long-term therapy with insulin (>30 days) within the last year
Therapy with rosiglitazone (Avandia) or pioglitazone (Actos), or extendin-4 (Byetta), alone or in combination in the previous 6 months
Pregnancy or lactation
Patients requiring corticosteroids within 3 months or recurrent continuous oral corticosteroid treatment (more than 2 weeks)
Use of weight loss drugs [e.g., Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanol-amine), or similar over-the-counter medications] within 3 months of screening or intentional weight loss of ≥ 10 lbs in the previous 6 months
Surgery within 30 days prior to screening
Serum creatinine >1.4 for women and >1.5 for men or eGFR <60 [possible chronic kidney disease stage 3 or greater calculated using the Modification of Diet in Renal Disease (MDRD) equation.
History of chronic liver disease including hepatitis B or C
History of peptic ulcer or endoscopy demonstrated gastritis
History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
History of malignancy, except participants who have been disease-free for greater than 10 years, or whose only malignancy has been basal or squamous cell skin carcinoma
New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure
History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack or any revascularization within 6 months
Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg or diastolic blood pressure >95 mmHg on three or more assessments on more than one day)
History of drug or alcohol abuse, or current weekly alcohol consumption >10 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 ounce of alcohol)
Hemoglobin <12 g/dL (males), <10 g/dL (females) at screening
Platelets <100,000 cu mm at screening.
AST (SGOT) >2.50 x ULN or ALT (SGPT) >2.50 x ULN at screening
Total Bilirubin >1.50 x ULN at screening
Triglycerides (TG) >500 mg/dL at screening
Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study
Previous allergy to aspirin
Chronic or continuous use (daily for more than 7 days) of nonsteroidal anti-inflammatory drugs within the preceding 2 months
Use of warfarin (Coumadin), clopidogrel (Plavix) or other anticoagulants
Use of probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or other uricosuric agents

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

3 gram

3.5 gram

4 gram

Arm Description

Placebo, appearance matched to active drug

Salsalate 3.0 grams daily, divided

Salsalate 3.5 g daily, divided

Salsalate 4.0 g daily, divided

Outcomes

Primary Outcome Measures

Change in HbA1c Baseline to End of Trial in TINSAL-T2D Stage 1

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.

Secondary Outcome Measures

Change in HbA1c

Change from baseline to either 14 or 26 weeks, or last HbA1c measurement prior to rescue therapy

Change From Baseline and Trends in Fasting Glucose Over Time

Change in Lipids

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) LDL-C/HDL-C ratio not calculated

Change From Baseline in 14-week Insulin, C-peptide, Homeostasis Model [HOMA] Index

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.

Safety and Tolerability

See adverse event module for details. Safety and tolerability of salsalate compared to placebo as assessed by adverse events.

Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index

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

Full Information

NCT ID

NCT00392678

First Posted

October 25, 2006

Last Updated

March 25, 2019

Sponsor

Joslin Diabetes Center

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT00392678

Brief Title

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

Acronym

TINSAL-T2D

Official Title

Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

October 2006 (undefined)

Primary Completion Date

July 2008 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Joslin Diabetes Center

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Growing evidence over recent years supports a potential role for low grade chronic inflammation in the pathogenesis of insulin resistance and type 2 diabetes. In this study we will determine whether salsalate, a member of the commonly used Non-Steroidal Anti-Inflammatory Drug (NSAID) class, is effective in lowering sugars in patients with type 2 diabetes. The study will determine whether salicylates represent a new pharmacological option for diabetes management. The study is conducted in two stages. The first stage is a dose ranging study, administering salsalate compared to placebo over three months. The primary objective of Stage 2 of the study is to evaluate the effects of salsalate on blood sugar control in diabetes; the tolerability of salsalate use in patients with type 2 diabetes (T2D); and the effects of salsalate on measures of inflammation, the metabolic syndrome, and cardiac risk. The second stage is a second trial and posted under alternate registration.

Detailed Description

The primary objective of the first stage of the TINSAL-T2D trial is to select a dose of salsalate that is both well-tolerated and demonstrates a trend toward improvement in glycemic control. The trial is a multicenter, single mask lead-in, double masked placebo controlled dose ranging study, comparing salsalte to placebo over 3 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes

Keywords

Type 2 Diabetes, Inflammation, Obesity, Metabolic Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

277 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo, appearance matched to active drug

Arm Title

3 gram

Arm Type

Active Comparator

Arm Description

Salsalate 3.0 grams daily, divided

Arm Title

3.5 gram

Arm Type

Active Comparator

Arm Description

Salsalate 3.5 g daily, divided

Arm Title

4 gram

Arm Type

Active Comparator

Arm Description

Salsalate 4.0 g daily, divided

Intervention Type

Drug

Intervention Name(s)

Salsalate

Other Intervention Name(s)

Disalcid, Salicylsalicylic acid

Intervention Description

Placebo and Salsalate 3.0 g/d; 3.5 g/d; 4.0 g/d orally, divided

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo to Salsalate

Intervention Description

Placebo to Salsalate

Primary Outcome Measure Information:

Title

Change in HbA1c Baseline to End of Trial in TINSAL-T2D Stage 1

Description

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.

Time Frame

14 week

Secondary Outcome Measure Information:

Title

Change in HbA1c

Description

Change from baseline to either 14 or 26 weeks, or last HbA1c measurement prior to rescue therapy

Time Frame

14 week

Title

Change From Baseline and Trends in Fasting Glucose Over Time

Time Frame

14 week

Title

Change in Lipids

Description

Time Frame

14 week

Title

Change From Baseline in 14-week Insulin, C-peptide, Homeostasis Model [HOMA] Index

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

Title

Safety and Tolerability

Description

See adverse event module for details. Safety and tolerability of salsalate compared to placebo as assessed by adverse events.

Time Frame

14 weeks

Title

Change in Insulin, C-peptide, Homeostasis Model [HOMA] Index

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Type 2 diabetes on diet and exercise therapy or monotherapy with metformin, insulin secretagogue, or alpha-glucosidase inhibitors, or a low-dose combination of these at ≤ 50% maximal dose (see Appendix). Dosing is stable for 8 weeks prior to randomization. FPG ≤ 225 mg/dL and HbA1c>7% and ≤9.5% at screening Age ≥18 and <75 Women of childbearing potential agree to use an appropriate contraceptive method (hormonal, IUD, or diaphragm) Exclusion Criteria: Type 1 diabetes and/or history of ketoacidosis determined by medical history History of severe diabetic neuropathy including autonomic neuropathy, gastroparesis or lower limb ulceration or amputation History of long-term therapy with insulin (>30 days) within the last year Therapy with rosiglitazone (Avandia) or pioglitazone (Actos), or extendin-4 (Byetta), alone or in combination in the previous 6 months Pregnancy or lactation Patients requiring corticosteroids within 3 months or recurrent continuous oral corticosteroid treatment (more than 2 weeks) Use of weight loss drugs [e.g., Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanol-amine), or similar over-the-counter medications] within 3 months of screening or intentional weight loss of ≥ 10 lbs in the previous 6 months Surgery within 30 days prior to screening Serum creatinine >1.4 for women and >1.5 for men or eGFR <60 [possible chronic kidney disease stage 3 or greater calculated using the Modification of Diet in Renal Disease (MDRD) equation. History of chronic liver disease including hepatitis B or C History of peptic ulcer or endoscopy demonstrated gastritis History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV) History of malignancy, except participants who have been disease-free for greater than 10 years, or whose only malignancy has been basal or squamous cell skin carcinoma New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack or any revascularization within 6 months Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg or diastolic blood pressure >95 mmHg on three or more assessments on more than one day) History of drug or alcohol abuse, or current weekly alcohol consumption >10 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 ounce of alcohol) Hemoglobin <12 g/dL (males), <10 g/dL (females) at screening Platelets <100,000 cu mm at screening. AST (SGOT) >2.50 x ULN or ALT (SGPT) >2.50 x ULN at screening Total Bilirubin >1.50 x ULN at screening Triglycerides (TG) >500 mg/dL at screening Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study Previous allergy to aspirin Chronic or continuous use (daily for more than 7 days) of nonsteroidal anti-inflammatory drugs within the preceding 2 months Use of warfarin (Coumadin), clopidogrel (Plavix) or other anticoagulants Use of probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or other uricosuric agents

Overall Study Officials: