Targeting Inflammation Using Salsalate for Type 2 Diabetes-Stage II (TINSALT2D-II)
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| ClinicalTrials.gov Identifier: NCT00799643 |
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Recruitment Status :
Completed
First Posted : December 1, 2008
Results First Posted : November 25, 2013
Last Update Posted : December 11, 2017
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Sponsor:
Joslin Diabetes Center
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Joslin Diabetes Center
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Type 2 Diabetes Mellitus | Drug: Salsalate Drug: Salsalate Placebo | Phase 2 Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 638 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Targeting Inflammation in Type 2 Diabetes: Clinical Trial Using Salsalate |
| Study Start Date : | November 2008 |
| Actual Primary Completion Date : | September 2012 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Type 2 diabetes
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 1
Salsalate, 3.5 g/d orally, divided dosing
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Drug: Salsalate
Salsalate 3.5 g/d orally, divided dosing
Other Name: disalsid |
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Placebo Comparator: 2
Salsalate Placebo, orally, divided dosing
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Drug: Salsalate Placebo |
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. [ Time Frame: 48 weeks from baseline ]HbA1c (%, percentage of HbA1c) change from baseline.
Secondary Outcome Measures :
- Change From Baseline in Fasting Glucose Over Time. [ Time Frame: 48 weeks from baseline ]
- 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 ]
- 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) [ Time Frame: 48 weeks ]
- Changes in WBC and Differential, High-sensitivity C Reactive Protein (hsCRP), Other Inflammatory Markers [ Time Frame: 24 and 48 weeks ]
- 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 ]
- Response Rates in Patients Initially Treated With Lifestyle Modification, Insulin Secretagogue, Metformin or Combination Therapy [ Time Frame: 24 and 48 weeks ]
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00799643
Locations
Show 21 study locations
Sponsors and Collaborators
Joslin Diabetes Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
| Principal Investigator: | Steven E. Shoelson, MD, PhD | Joslin Diabetes Center | |
| Study Director: | Allison B. Goldfine, MD | Joslin Diabetes Center | |
| Study Director: | Vivian Fonseca, MD | Tulane University | |
| Study Director: | Kathleen Jablonski, PhD | George Washington University | |
| Study Director: | Myrlene Staten, MD | National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) |
Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Joslin Diabetes Center |
| ClinicalTrials.gov Identifier: | NCT00799643 |
| Other Study ID Numbers: |
CHS 06-20-2 U01DK074556 ( U.S. NIH Grant/Contract ) |
| First Posted: | December 1, 2008 Key Record Dates |
| Results First Posted: | November 25, 2013 |
| Last Update Posted: | December 11, 2017 |
| Last Verified: | November 2017 |
Keywords provided by Joslin Diabetes Center:
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Type 2 Diabetes Mellitus (T2D) Inflammation Obesity Metabolic Syndrome Salicylates |
Additional relevant MeSH terms:
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Diabetes Mellitus Diabetes Mellitus, Type 2 Inflammation Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Pathologic Processes Salicylsalicylic acid Sodium Salicylate Anti-Inflammatory Agents, Non-Steroidal |
Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Cyclooxygenase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |