Effect of Salicylate on Glucose Metabolism in Insulin Resistance States

NCT00258128 | Completed Phase 1 Results

• 3 other identifiers: CHS 00-01R37DK051729R01DK051729
• Study Type: interventional
• Target: 17
• Locations: 0 countries
• Sites: N/A

Brief Summary

Data supports diet induced obesity leads to activation of the IKK/NF-kB inflamatory pathway and that chronic inflammation leads to insulin resistance and diabetes. In rodents, salicylates inhibit IKK/NF-kB and may improve insulin sensitivity. We will study if this is true in people.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Glucose

  fasting glucose

  4 weeks

Secondary Outcomes (1)

• Adiponectin

  4 weeks

Study Arms (2)

Treatment

EXPERIMENTAL

This third small study has a randomized, masked, placebo controlled parallel design to compare salsalate 4.0 g/d to placebo. This is the salsalate 4.0 g/d arm.

Drug: Salsalate

Placebo

PLACEBO COMPARATOR

This third small study has a randomized, masked, placebo controlled parallel design to compare salsalate 4.0 g/d to placebo. This is the placebo arm.

Drug: Placebo

Interventions

Salsalate DRUG

Active

Also known as: Disalcid

Treatment

Placebo DRUG

Placebo for salslate, used only in the third trial

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age 18 to 65 years, inclusive; HbA1c \>6.0% (off medication-diabetic) normal hemoglobin and hematocrit, without donation of blood in the previous 2 months; without involvement in any study evaluating an investigational drug or device for the previous 2 months; normal clotting studies; female postmenopausal or surgically sterile, or using barrier or oral contraception and with a negative pregnancy test.

You may not qualify if:

• pregnant or lactating women; patients with persistent ketonuria or a history of ketoacidosis (suggesting the need for insulin therapy); current of previous use of insulin for glucose control; patients with abnormal liver function defined as elevation of bilirubin, alkaline phosphatase, ALT, AST, or GGTP more than 1.5 times the upper limit of normal; patients with kidney disease (serum creatinine \> 1.5 mg/dL) macroalbuminuria (1+ protein on a standard urine dip-stick, or \> 300 mg urinary albumin/day)- (patients with microalbuminuria will be enrolled); patients with any significant diseases or conditions, including emotional or psychiatric disorders and substance abuse, including history of binge drinking, that, in the opinion of the investigator, are likely to alter the patient's ability to complete the study; patients with metabolic acidosis (abnormal anion gap); history of gastric ulcer, dyspepsia, or upper or lower GI bleed; history of allergy to aspirin, or bleeding diathesis or currently on oral anticoagulants including warfarin, heparin, aspirin or other NSAIDs; patients with major vascular event within 6 months of screening for the study (e.g., myocardial infarction stroke, coronary artery bypass graft (CABG) surgery, angioplasty, peripheral vascular surgery); patients with chronic heart disease, or a history of myocardial infarction or stroke. Symptomatic angina pectoris or cardiac insufficiency as defined by the NYHA; classification as Functional Class III or IV; patients with HbA1C \> 13% (normal range 4-6%); patients who smoke more than one pack of cigarettes daily; patients taking treatment medications known to affect insulin sensitivity (e.g. diuretics, beta-blockers); patients taking warfarin, heparin or NSAID on a chronic basis; patients with inadequately controlled serum lipid levels (total cholesterol ≥ 275 mg/dL and fasting triglycerides ≥ 450 mg/dL); patients with history of cancer within 5 years prior to screening for the study other than basal cell carcinoma; active alcohol or other substance abuse.

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Related Publications (3)

• Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008 Feb;31(2):289-94. doi: 10.2337/dc07-1338. Epub 2007 Oct 24.

  PMID: 17959861 BACKGROUND

• Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. doi: 10.1172/JCI29069.

  PMID: 16823477 BACKGROUND

• Goldfine AB, Silver R, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci. 2008 May;1(1):36-43. doi: 10.1111/j.1752-8062.2008.00026.x.

  PMID: 19337387 RESULT

MeSH Terms

Conditions

Insulin Resistance

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Small study size, sort duration of treatment, multiple endpoints. See manuscript: Goldfine AB, et al. Clin Transl Sci. 2008 May;1(1):36-43.

Results Point of Contact

• Title: Allison B. Goldfine, MD
• Organization: Joslin Diabetes Center

allison.goldfine@joslin.harvard.edu

617-309-2400

Study Officials

• Steven Shoelson

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2005
• First Posted: November 24, 2005
• Study Start: January 1, 2000
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: April 30, 2019
• Results First Posted: April 30, 2019

Record last verified: 2019-04