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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Clifton Bogardus, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00339833
First received: June 19, 2006
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Diabetes
Drug: Salsalate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Salsalate Treatment on Insulin Sensitivity and Insulin Secretion in Obese Non-Diabetic Individuals

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change in Fasting Plasma Glucose Concentration [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Change in the Average Serum Insulin Concentration During the Last 40 Min of Clamp [ Time Frame: last 40 min of clamp ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: March 2003
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Salsalate
Salsalate (3g/day) for 7 days
Drug: Salsalate
The intervention was salsalate (3g/day) for 7 days.
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Identical placebo for 7 days.

Detailed Description:

In healthy subjects, low-grade inflammation, as measured by serum levels of cytokines or acute phase proteins, is positively associated with adiposity. Recent studies indicate that chronic low-grade inflammation in non-diabetic individuals may cause decline in insulin sensitivity and increases the risk of developing type 2 diabetes. It has been proposed that reduction of low-grade inflammation may reduce the risk of development of type 2 diabetes. In agreement with this hypothesis, the class of anti-inflammatory drugs called salicylates (such as aspirin) that influence a specific anti-inflammatory pathway have been found to decrease plasma glucose levels and increase insulin sensitivity in rodents as well as people with type 2 diabetes.

In the present study, we propose testing whether administration of the anti-inflammatory drug Salsalate improves insulin sensitivity in obese non-diabetic individuals and whether this improvement is related with a decrease in serum markers of inflammation. Subjects will be randomly assigned to two treatment groups: placebo or Salsalate (3g/d). An oral glucose tolerance test and a combined euglycemic/hyperglycemic clamp to assess insulin sensitivity and insulin secretion will be performed before and after seven days of treatment. Results of this study may help to identify novel strategies to prevent type 2 diabetes in high-risk groups.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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)

EXCLUSION CRITERIA:

  • 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.
  • History of metabolic acidosis.
  • Allergy to aspirin, other salicylates, or bleeding diathesis or currently on oral anticoagulants.
  • Any current viral illness.
  • Active cancer within 5 years prior to screening for the study.
  • Positive urine drug screening test.
  • Inability to provide informed consent.
  • Smokers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00339833

Locations
United States, Arizona
NIDDK, Phoenix
Phoenix, Arizona, United States, 85014
Sponsors and Collaborators
Investigators
Principal Investigator: Bogardus Clifton, MD National Institues of Diabetes and Digestive and Kidney Disease
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Clifton Bogardus, Principal Investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00339833     History of Changes
Other Study ID Numbers: 999903121, 03-DK-N121, 03-DK-N121
Study First Received: June 19, 2006
Results First Received: December 29, 2010
Last Updated: January 29, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Salsalate
Insulin Resistance
Diabetes Mellitus
Inflammation
Diabetes
HCV

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Insulin
Sodium Salicylate
Salicylsalicylic acid
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 23, 2014