CompletedNCT00339833Updated Mar 6, 2013Results posted

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

A Phase 4 interventional study of Salsalate and Placebo in Type 2 Diabetes and Diabetes, sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Completed at 1 site in United States. Open to participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2013-03-06.

Sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 54
Allocation: Randomized
Ages: 18 Years to 45 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Type 2 Diabetes
Diabetes

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Keywords

Salsalate
Insulin Resistance
Diabetes Mellitus
Inflammation
Diabetes
HCV

In context

Diabetes Mellitus, Type 2

9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.

This study's enrollment of 54 is below the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.

Browse Diabetes Mellitus, Type 2 studies →

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is the lead sponsor of 537 studies on the registry; 54 are open to participants now.

Of its 80 completed or terminated interventional studies of FDA-regulated products, 51 (64%) have results posted.

Browse National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 54 participants (actual)

Study arms

Experimental
Salsalate
Salsalate (3g/day) for 7 days
Drug: Salsalate
Placebo comparator
Placebo
Placebo
Drug: Placebo

Interventions

DrugSalsalate
The intervention was salsalate (3g/day) for 7 days.
DrugPlacebo
Identical placebo for 7 days.

What researchers measure

Primary outcomes

Change in Fasting Plasma Glucose Concentration
Time frame: 7 days
Change in the Average Serum Insulin Concentration During the Last 40 Min of Clamp
Time frame: last 40 min of clamp

Results

Posted Mar 6, 2013

Participant flow

Recruitment location: clinical research unit at the NIDKK (Phoenix, AZ, USA)

Participant flow — Overall Study
Milestone	Salsalate	Placebo
Started	28	26
Completed	22	18
Not completed	6	8
Withdrew: Withdrawal by subject	1	2
Withdrew: Toothache	0	1
Withdrew: Indigestion	0	1
Withdrew: Chest pain	0	1
Withdrew: Minor infection	0	1
Withdrew: Poor venous access	2	2
Withdrew: Anaemia or excess drop in glycaemia	2	0
Withdrew: Error in data records	1	0

Outcome measures

PrimaryChange in Fasting Plasma Glucose Concentration

Time frame:: 7 days
Reported as:: Mean · mmol/l

Change in Fasting Plasma Glucose Concentration
mmol/l	Salsalate	Placebo
Change in Fasting Plasma Glucose Concentration	4.7 ± 6.5	0.0 ± 3.7

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

Time frame:: last 40 min of clamp
Reported as:: Mean · l/min

Change in the Average Serum Insulin Concentration During the Last 40 Min of Clamp
l/min	Salsalate	Placebo
Change in the Average Serum Insulin Concentration During the Last 40 Min of Clamp	0.15 ± 0.21	-0.06 ± 0.23

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Salsalate	—	0/22 (0%)	0/22 (0%)
Placebo	—	0/18 (0%)	0/18 (0%)

Baseline characteristics

Age Continuous
Age Continuous(years)	Salsalate	Placebo	Total
Mean	29 ± 7	33 ± 8	31 ± 7.5

Sex: Female, Male
Sex: Female, Male(Participants)	Salsalate	Placebo	Total
Female	12	9	21
Male	10	9	19

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	Salsalate	Placebo	Total
Hispanic	0	1	1
White	3	3	6
Native American	19	14	33

Region of Enrollment
Region of Enrollment(participants)	Salsalate	Placebo	Total
United States	22	18	40

BMI
BMI(kg/m2)	Salsalate	Placebo	Total
Mean	37 ± 5	38 ± 6	37.5 ± 5.5

Body Fat
Body Fat(% body fat)	Salsalate	Placebo	Total
Mean	38 ± 6	38 ± 7	38 ± 6.5

Fasting plasma glucose
Fasting plasma glucose(mmol/l)	Salsalate	Placebo	Total
Median	5.11 ± 0.33	5.06 ± 0.33	5.09 ± 0.33

2 hour plasma glucose
2 hour plasma glucose(mmol/l)	Salsalate	Placebo	Total
Mean	6.67 ± 1.17	6.61 ± 1.83	6.64 ± 1.50

3 further baseline measures are reported on the registry.

Study locations

1 site

NIDDK, Phoenix
Phoenix, Arizona 85014, United States

References and documents

Publications

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. PubMed 11445664 ↗
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. PubMed 8653533 ↗
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. PubMed 9794114 ↗
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. PubMed 19104769 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 6, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00339833
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Responsible party: Clifton Bogardus (Principal Investigator, National Institutes of Health Clinical Center (CC)) — Principal investigator
First posted: Jun 21, 2006
Start date: Mar 2003
Primary completion: Jul 2008
Completion: Jul 2008
Results posted: Mar 6, 2013
Last update: Mar 6, 2013

Study contacts

Bogardus Clifton, MD

principal investigator · National Institues of Diabetes and Digestive and Kidney Disease

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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