Salsalate Therapy to Reduce Insulin Resistance and Cardiovascular Risk

NCT00330733 | Completed Phase 2 Results DMC

• 1 other identifier: CLIN-011-05F
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The hypothesis is that salsalate therapy may be an effective and safe method to modulate inflammation in metabolically-critical tissues and thus reduce insulin resistance and its related complications. The objectives of the study are to (1) determine whether salsalate therapy improves insulin resistance in subjects with IGT and changes in glucose area under the curve following a standard oral glucose tolerance test (OGTT); (2) determine whether salsalate therapy reduces a) plasma levels of a variety of well established inflammatory proteins and b) mononuclear cell inflammatory activity to provide evidence of reduced systemic and tissue inflammation, respectively; and (3)also determine whether salsalate therapy improves parameters of cardiovascular disease risk, including features of metabolic syndrome (fasting glucose, triglycerides, HDL, and blood pressure) as well as endothelial dysfunction.

Conditions

Atherosclerosis; Cardiovascular Disease; Inflammation; Insulin Resistance; Noninsulin-dependent Diabetes Mellitus

Keywords

Cardiovascular Disease; Inflammation; Insulin Resistance; Type 2 DM

Outcome Measures

Primary Outcomes (1)

• Change in Systemic Glucose Disposal- Glucose Infusion Rates

  Participants were admitted to the Clinical Research Units at 06:00-08:00 hours after an overnight fast. Euglycaemic-hyperinsulinaemic clamps were conducted at baseline and at the end of the study. Because salsalate therapy appears to decrease insulin clearance leading to higher circulating insulin levels during the clamp, we reduced the infusion rate of insulin in the active treatment arm by 20% (from 100 to 80 mUm-2 min-1) at the study end. Insulin solutions were prepared by the site pharmacist so that study staff remained blinded to drug assignment. Whole-body insulin sensitivity was estimated from glucose infusion rate (GIR) during last 30 min of insulin infusions.

  3 months

Secondary Outcomes (6)

• Glucose Area Under the Curve in These Subjects

  3 months

• Plasma CRP

  8 and 12 weeks

• Endothelial Function

  Baseline and 12 weeks

• Plasma Interleukin 6

  8 and 12 weeks

• Plasma sVCAM

  8 and 12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Salsalate Therapy

ACTIVE COMPARATOR

Salsalate

Drug: Salsalate

Interventions

Salsalate DRUG

Participants were randomized to 12-week treatment with up to 4 g/day.

Also known as: Amigesic, Anaflex, Argesic-SA, Disalcid, Marthritic, Mono-Gesic, Salflex, Salsitab

Salsalate Therapy

Placebo DRUG

Participants were randomized to 12-week treatment matching the active salsalate arm.

Placebo

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female veterans between the age of 21-75 who have IFG (impaired fasting glucose) and/or IGT

You may not qualify if:

• any diabetes therapy in the prior 12-months period
• any acute illness
• Ongoing high dose aspirin or Salsalate Therapy
• history of GI bleeding
• hearing problems
• poor vascular access, prior pancreatitis, uncontrolled hypertension, pregnancy, renal disease or anemia

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Joslin Diabetes Center: collaborator

Study Sites (1)

Carl T. Hayden VA Medical Center

Phoenix, Arizona, 85012, United States

Location

Related Publications (1)

• Goldfine AB, Conlin PR, Halperin F, Koska J, Permana P, Schwenke D, Shoelson SE, Reaven PD. A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance. Diabetologia. 2013 Apr;56(4):714-23. doi: 10.1007/s00125-012-2819-3. Epub 2013 Jan 31.

  PMID: 23370525 RESULT

MeSH Terms

Conditions

Atherosclerosis; Cardiovascular Diseases; Inflammation; Insulin Resistance; Diabetes Mellitus, Type 2

Interventions

salicylsalicylic acid; Sodium Salicylate; polynoxylin

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Salicylic Acid; Salicylates; Hydroxybenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Limitations and Caveats

Since we did not measure endogenous glucose production and lipolysis, the effects on hepatic glucose and lipid metabolism deserve further study. Sufficient numbers of women were not included, with which to confidently extend these results to women

Results Point of Contact

• Title: Peter Reaven
• Organization: Phoenix VA Health Care System

Peter.Reaven@va.gov

602 277 5551

Study Officials

• Peter Reaven, MD

  Carl T. Hayden VA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2006
• First Posted: May 29, 2006
• Study Start: January 1, 2007
• Primary Completion: August 1, 2010
• Study Completion: September 1, 2010
• Last Updated: January 21, 2020
• Results First Posted: April 22, 2014

Record last verified: 2020-01

Locations

US (1)