The Effects of Anti-Inflammatory Treatment on Insulin Resistance in Healthy Volunteers

NCT00339833 | Completed Phase 4 Results

• 2 other identifiers: 99990312103-DK-N121
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This study, conducted at the Phoenix Indian Medical Center, Phoenix, Arizona, will determine whether reducing subclinical inflammation lessens insulin resistance in healthy, obese volunteers. The study findings may lead to new strategies for preventing type 2 diabetes. In diabetes, blood sugar is higher than normal and can result in serious medical problems, such as blindness and kidney failure. People with subclinical inflammation-inflammation that does not produce symptoms, such as fever, pain, or skin redness-are at increased risk for diabetes. Although the reasons for this are not completely understood, it is known that subclinical inflammation exacerbates insulin resistance, which is a cause of diabetes. Insulin is a hormone that helps control blood sugar, and when it does not work properly, the condition is known as insulin resistance. Normal, healthy volunteers between 18 and 45 years old with a body mass index of at least 30 kg/m2 and who have subclinical inflammation (determined by blood tests) may be eligible for this study. Candidates must be non-smokers and must not have an alcohol or drug problem. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Participants will maintain a standard diet and undergo tests and procedures during a 14-day inpatient stay at the Phoenix Indian Medical Center.

Conditions

Type 2 Diabetes; Diabetes

Keywords

Salsalate; Insulin Resistance; Diabetes Mellitus; Inflammation; Diabetes; HCV

Outcome Measures

Primary Outcomes (2)

• Change in Fasting Plasma Glucose Concentration

  7 days

• Change in the Average Serum Insulin Concentration During the Last 40 Min of Clamp

  last 40 min of clamp

Study Arms (2)

Salsalate

EXPERIMENTAL

Salsalate (3g/day) for 7 days

Drug: Salsalate

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Salsalate DRUG

The intervention was salsalate (3g/day) for 7 days.

Salsalate

Placebo DRUG

Identical placebo for 7 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: Greater than 18 and less than 45 years.
• Number: 44 completed studies (22 placebo, 22 Salsalate).
• Sex: 22 Males and 22 Females.
• BMI: Greater than or equal to 30 kg.m(2)

You may not qualify if:

• Age below 18 or above 45 years to minimize the risk of glucose clamp.
• Diabetes mellitus (as per 75 g OGTT, WHO 1999 criteria)
• Cardiovascular disease including: abnormal EKG, personal history of coronary heart disease;symptomatic angina pectoris or cardiac insufficiency as defined by NYHA; classification as functional class III or IV.
• Systolic blood pressure greater than 160mmHG and/or diastolic blood pressure greater than 100 mmHg and/or on antihypertensive therapy or resting heart rate greater than 90 bpm.
• Hematological disorder, including prolonged prothrombin time (normal range 10.9-12.9 sec) and partial thromboplastin time (24-36 sec) and thrombocytopenia (less than 150,000 mm(3)).
• Respiratory disease (including influenza, asthma)
• Allergies (including hay fever)
• Gastrointestinal (including peptic ulcer), hepatic or renal disease (ALT and AST greater than 3-fold above upper limit of normal range, creatinine greater than 1.3 mg/dl).
• Alcoholism, alcohol-induced autonomic neuropathy.
• Any endocrinological disorder, including hypopituitarism/pituitary dysfunctions or lesions, hypo/hyperthyroidism, insulinoma.
• CNS disease
• Psychosis or personal history of any psychiatric disorder.
• Taking medications within one month prior to beginning the study, including medications known to have pharmacological interactions with salicylates or that may affect insulin sensitivity and secretion (including salicylates, COX 1 and COX 2 inhibitors, warfarin, Beta-Blockers, phenothiazines, antidepressants, antiarrhythmic drugs, antimuscarinic drugs).
• Acute inflammation as assessed by history, physical and laboratory examination (subjects with C-reactive protein 2 standard deviations above the population mean will not be admitted). The population mean was calculated from subjects admitted at our research unit.
• Pregnant or lactating females or females on hormonal contraceptives.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

NIDDK, Phoenix

Phoenix, Arizona, 85014, United States

Location

Related Publications (4)

• Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, Pratley RE. Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obes Res. 2001 Jul;9(7):414-7. doi: 10.1038/oby.2001.54.

  PMID: 11445664 BACKGROUND

• Pratley RE, Wilson C, Bogardus C. Relation of the white blood cell count to obesity and insulin resistance: effect of race and gender. Obes Res. 1995 Nov;3(6):563-71. doi: 10.1002/j.1550-8528.1995.tb00191.x.

  PMID: 8653533 BACKGROUND

• Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia. 1998 Oct;41(10):1241-8. doi: 10.1007/s001250051058.

  PMID: 9794114 BACKGROUND

• Koska J, Ortega E, Bunt JC, Gasser A, Impson J, Hanson RL, Forbes J, de Courten B, Krakoff J. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia. 2009 Mar;52(3):385-93. doi: 10.1007/s00125-008-1239-x. Epub 2008 Dec 23.

  PMID: 19104769 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Insulin Resistance; Inflammation

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jonathan Krakoff, M.D./National Institute of Diabetes and Digestive and Kidney Diseases
• Organization: National Institutes of Health

jkrakoff@mail.nih.gov

6022005217

Study Officials

• Bogardus Clifton, MD

  National Institues of Diabetes and Digestive and Kidney Disease

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 19, 2006
• First Posted: June 21, 2006
• Study Start: March 1, 2003
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: March 6, 2013
• Results First Posted: March 6, 2013

Record last verified: 2013-01

Locations

US (1)