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Targeting Inflammation Using Salsalate for Type 2 Diabetes-Stage II (TINSALT2D-II)

Primary Purpose

Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Salsalate

Salsalate Placebo

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Type 2 Diabetes Mellitus (T2D), Inflammation, Obesity, Metabolic Syndrome, Salicylates

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 (including SFU, non-SFU, and dipeptidyl peptidase IV (DPP-4) inhibitors), alpha-glucosidase inhibitors, or bile acid sequestrants (dosed once per day such that study drug can be administered ≥ 4 hours prior to sequestrant); or a combination of up to two of these at maximal dose. Dosing must be stable for 8 weeks prior to screening. Participant must have been diagnosed with T2D at least 8 weeks before screening.
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:

No prior participation in Stage I of TINSAL-T2D ; exception: a participant who failed screening for HbA1c in Stage I will be allowed to re-screen for Stage II.
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), alone or in combination in the previous 6 months; or exendin-4 (Byetta), alone or in combination in the previous 3 months
Pregnancy or lactation
Patients requiring oral 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). If on blood pressure medications, dosing should be stable for 2 weeks prior to randomization.
History of drug or alcohol abuse, or current weekly alcohol consumption >10 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed DCCktail 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), dipyridamole (Persantine), heparin or other anticoagulants
Use of probenecid (Benemid, probalan), sulfinpyrazone (Anturane) or other uricosuric agents
Macroalbuminuria, defined as spot urine protein >300 mcg/mg Cr at screening
Pre-existing chronic tinnitus

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

Salsalate, 3.5 g/d orally, divided dosing

Salsalate Placebo, orally, divided dosing

Outcomes

Primary Outcome Measures

The Primary Outcome for the TINSAL-T2D Study is Change in HbA1c Level From Baseline to Week 48 From Baseline, Compared Between Treatment Groups.

HbA1c (%, percentage of HbA1c) change from baseline.

Secondary Outcome Measures

Change From Baseline in Fasting Glucose Over Time.

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%

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)

Changes in WBC and Differential, High-sensitivity C Reactive Protein (hsCRP), Other Inflammatory Markers

Response Rates for Exceeding Hyperglycemic Targets Between Active and Placebo Treated Groups; Need for Rescue Therapy; Need for Discontinuation of Study Medication

Response Rates in Patients Initially Treated With Lifestyle Modification, Insulin Secretagogue, Metformin or Combination Therapy

Full Information

NCT ID

NCT00799643

First Posted

November 26, 2008

Last Updated

November 8, 2017

Sponsor

Joslin Diabetes Center

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00799643

Brief Title

Targeting Inflammation Using Salsalate for Type 2 Diabetes-Stage II

Acronym

TINSALT2D-II

Official Title

Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate

Study Type

Interventional

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Completed

Study Start Date

November 2008 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

undefined (undefined)

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. Enrollment in the first stage is complete. The primary objective of the first stage was to select a dose of salsalate that is both well-tolerated and demonstrates a trend toward improvement in glycemic control. 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.

6. Conditions and Keywords

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

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus (T2D), Inflammation, Obesity, Metabolic Syndrome, Salicylates

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

638 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Salsalate, 3.5 g/d orally, divided dosing

Arm Title

Arm Type

Placebo Comparator

Arm Description

Salsalate Placebo, orally, divided dosing

Intervention Type

Drug

Intervention Name(s)

Salsalate

Other Intervention Name(s)

disalsid

Intervention Description

Salsalate 3.5 g/d orally, divided dosing

Intervention Type

Drug

Intervention Name(s)

Salsalate Placebo

Primary Outcome Measure Information:

Title

The Primary Outcome for the TINSAL-T2D Study is Change in HbA1c Level From Baseline to Week 48 From Baseline, Compared Between Treatment Groups.

Description

HbA1c (%, percentage of HbA1c) change from baseline.

Time Frame

48 weeks from baseline

Secondary Outcome Measure Information:

Title

Change From Baseline in Fasting Glucose Over Time.

Time Frame

48 weeks from baseline

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%

Time Frame

24 and 48 weeks

Title

Time Frame

48 weeks

Title

Changes in WBC and Differential, High-sensitivity C Reactive Protein (hsCRP), Other Inflammatory Markers

Time Frame

24 and 48 weeks

Title

Response Rates for Exceeding Hyperglycemic Targets Between Active and Placebo Treated Groups; Need for Rescue Therapy; Need for Discontinuation of Study Medication

Time Frame

24 and 48 weeks

Title

Response Rates in Patients Initially Treated With Lifestyle Modification, Insulin Secretagogue, Metformin or Combination Therapy

Time Frame

24 and 48 weeks

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 (including SFU, non-SFU, and dipeptidyl peptidase IV (DPP-4) inhibitors), alpha-glucosidase inhibitors, or bile acid sequestrants (dosed once per day such that study drug can be administered ≥ 4 hours prior to sequestrant); or a combination of up to two of these at maximal dose. Dosing must be stable for 8 weeks prior to screening. Participant must have been diagnosed with T2D at least 8 weeks before screening. 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: No prior participation in Stage I of TINSAL-T2D ; exception: a participant who failed screening for HbA1c in Stage I will be allowed to re-screen for Stage II. 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), alone or in combination in the previous 6 months; or exendin-4 (Byetta), alone or in combination in the previous 3 months Pregnancy or lactation Patients requiring oral 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). If on blood pressure medications, dosing should be stable for 2 weeks prior to randomization. History of drug or alcohol abuse, or current weekly alcohol consumption >10 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed DCCktail 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), dipyridamole (Persantine), heparin or other anticoagulants Use of probenecid (Benemid, probalan), sulfinpyrazone (Anturane) or other uricosuric agents Macroalbuminuria, defined as spot urine protein >300 mcg/mg Cr at screening Pre-existing chronic tinnitus

Overall Study Officials: