Beneficial Effect of Salicylates: Insulin Action, Secretion or Clearance?

The possibility that obesity-associated inflammatory changes may play a role in the pathogenesis of type 2 diabetes (2DM) has led to increased interest in the possibility that salicylates might represent a useful treatment to improve glucose tolerance. Several studies, performed in patients with 2DM, as well as in nondiabetic, obese individuals, have demonstrated that salicylates have beneficial effects on glucose and insulin metabolism, but have not led to a coherent view as to the mechanism(s) involved.

In this research proposal we will use specific methods to quantify insulin mediated glucose uptake (IMGU), glucose-stimulated insulin secretion rate (GS-ISR), and insulin clearance (I-Cl) in overweight/obese, nondiabetic, insulin resistant individuals. We will use the insulin suppression test (IST) to quantify IMGU in nondiabetic, overweight/obese volunteers to identify those individuals who are sufficiently insulin resistant to be enrolled in this study. We will then use the graded glucose infusion technique in these insulin resistant subjects to generate specific measures of both GS-IS and I-Cl. Following these baseline measurements, salsalate or placebo will be administered for one month to the participants, after which time the IST and the graded glucose infusion will be repeated to quantify and compare the changes in IMGU, GS-ISR, and I-Cl that have resulted from salsalate versus placebo. These results will provide for the first time quantitative data of the effect of salicylates on IMGU, GS-ISR, and I-Cl in overweight/obese, insulin resistant, nondiabetic individuals.

Study Overview

• Status: Completed
• Conditions: Pre Diabetes; Insulin Resistant
• Intervention / Treatment: Drug: salsalate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers,
• BMI 25-35kg/m2,
• Without severe anemia, kidney, liver disease or any current GI ulcers or bleeding
• Or on any medication contraindicated with salsalate

Exclusion Criteria:

• Recent history of GI bleed or ulcers,
• CVD or on anticoagulants
• Severe kidney or liver disease
• Allergies to aspirin
• Taking aspirin or anti inflammatory medication on a regular basis and cannot be taken off for the duration of the study

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: salsalate 3500mg in 2 divided doses a day; Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner	Drug: salsalate; Participants will take 3, 500 mg tablets with breakfast and 4, 500 mg tablets with dinner
PLACEBO_COMPARATOR: placebo; Participants will take 3 placebo tablets with breakfast and 4 placebo tablets with dinner	Drug: Placebo; Participants will take 3 tablets with breakfast and 4 tablets with dinner

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of Insulin Action With the Insulin Suppression Test (IST)	Compare changes in insulin sensitivity as assesses by the IST before and after treatment between salsalate and placebo group	after treatment for one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of Insulin Clearance With the Graded Glucose Infusion Test (GGIT)	compare changes in insulin clearance as assessed by the GGIT before and after treatment with salsalate to placebo	one month on treatment

Collaborators and Investigators

• Sponsor: Stanford University

Publications and helpful links

General Publications

• Kim SH, Liu A, Ariel D, Abbasi F, Lamendola C, Grove K, Tomasso V, Ochoa H, Reaven G. Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study. Diabetes Care. 2014 Jul;37(7):1944-50. doi: 10.2337/dc13-2977.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: March 5, 2013
• First Submitted That Met QC Criteria: December 9, 2013
• First Posted (ESTIMATE): December 11, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): May 5, 2016
• Last Update Submitted That Met QC Criteria: April 1, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: insulin resistant
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Salicylsalicylic acid
• Other Study ID Numbers: 19254

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO