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Assessment of the Effects of a DPP-4 Inhibitor (Sitagliptin) Januvia on Immune Function in Healthy Individuals

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00813228
First received: December 19, 2008
Last updated: March 14, 2014
Last verified: January 2014

December 19, 2008
March 14, 2014
December 2008
Not Provided
Changes in plasma TGF-Beta 1 levels.
Same as current
Complete list of historical versions of study NCT00813228 on ClinicalTrials.gov Archive Site
Changes in plasma or stimulated PBMC cytokines levels, changes in stimulated PBMC proliferation, changes in peripheral blood gene expression and changes in immune phenotyping.
Same as current
Not Provided
Not Provided
 
Assessment of the Effects of a DPP-4 Inhibitor (Sitagliptin) Januvia on Immune Function in Healthy Individuals
Assessment of the Effects of a DPP-4 Inhibitor (Sitagliptin) Januvia on Immune Function in Healthy Individuals

Patients with diabetes have high blood sugar levels (hyperglycemia) because pancreatic beta-cells no longer produce sufficient insulin. Insufficient beta-cell function can be caused by an autoimmune killing of the beta-cells in type 1 diabetes (T1D), or by poorly understood mechanisms in type 2 diabetes (T2D). Glucagon-like peptide-1 (GLP-1) improves function of the insulin-producing beta cells, but GLP-1 has a very short circulating half-life because it is cleaved by the enzyme dipeptidyl peptidase IV (DPP-4). One current treatment being used to improve glycemia control in patients with T2D is sitagliptin, an inhibitor of DPP-4. By inhibiting DPP-4, sitagliptin increases GLP-1 levels, resulting in improved beta cell function. Sitagliptin is now being tested in individuals with new-onset T1D to determine whether it may help to preserve beta cell function. Because T1D is a disease in which the immune system destroys the insulin-producing beta cells in the pancreas, we wish to determine if and how sitagliptin alters immune function. Sitagliptin has been shown by Merck to be safe and effective with no overt immuno-toxicities. However, several lines of evidence suggest that DPP-4 inhibitors such as sitagliptin could be immunomodulatory.

This randomized clinical trial will study immune function in healthy volunteers given short-term (4 week) treatment with either sitagliptin or placebo. During the study, we will take blood samples at various time intervals before, during and after treatment. We will compare the immune response with and without sitagliptin treatment using blood samples from healthy individuals. We will measure changes in the magnitude and type of immune responses. The study period is nine weeks. The study s primary outcome will be changes in blood plasma levels of a protein marker associated with decreased inflammation: Transforming Growth Factor Beta 1 (TGF beta 1). In addition, we plan to use these blood samples to measure sitagliptin s effect on expression levels of several cytokines (immune proteins). We will also measure the level of proliferation in stimulated PBMCs (blood immune cells) and gene expression in whole blood after sitagliptin treatment.

Patients with diabetes have high blood sugar levels (hyperglycemia) because pancreatic b-cells no longer produce sufficient insulin. Insufficient b-cell function can be caused by an autoimmune killing of the b-cells in type 1 diabetes (T1D), or by poorly understood mechanisms in type 2 diabetes (T2D). Glucagon-like peptide -1 (GLP-1) improves function of the insulin-producing beta cells, but GLP-1 has a very short circulating half-life because it is cleaved by the enzyme dipeptidyl peptidase IV (DPP-4). One current treatment being used to improve glycemia control in patients with T2D is sitagliptin, an inhibitor of DPP-4. By inhibiting DPP-4, sitagliptin increases GLP-1 levels resulting in improved beta cell function. Sitagliptin is now being tested in individuals with new-onset T1D to determine whether it may help to preserve beta cell function. Because T1D is a disease in which the immune system destroys the insulin-producing beta cells in the pancreas, we wish to determine if and how sitagliptin alters immune function. Sitagliptin has been shown by Merck to be safe and effective with no overt immuno-toxicities. However, several lines of evidence suggest that DPP-4 inhibitors such as sitagliptin could be immunomodulatory.

This randomized clinical trial will study immune function in healthy volunteers given short-term (4 week) treatment with either sitagliptin or placebo. During the study, we will take blood samples at various time intervals before, during and after treatment. We will compare the immune response with and without sitagliptin treatment using blood samples from healthy individuals. We will measure changes in the magnitude and type of immune responses. The study period is nine weeks. The study s primary outcome will be changes in blood plasma levels of a protein marker associated with decreased inflammation: Transforming Growth Factor-Beta1 (TGFb1). In addition, we plan to use these blood samples to measure sitagliptin s effect on expression levels of several cytokines (immune proteins). We will also measure the level of proliferation in stimulated PBMCs (blood immune cells) and gene expression in whole blood after sitagliptin treatment.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
  • Diabetes Mellitus Type 1
  • Diabetes Mellitus Type 2
Drug: Sitagliptin (Januvia)
N/A
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
76
June 2011
Not Provided
  • INCLUSION CRITERIA:

Age greater than 18

Fasting blood glucose less than 100 mg/dl, and a normal Hgb A1c (less than 5.7%),

Available for follow up through 9 weeks.

In good general health without clinically significant medical history as deemed by study investigators.

EXCLUSION CRITERIA:

History of diabetes or other autoimmune diseases including (but not limited to) rheumatoid arthritis, lupus, multiple sclerosis.

Active hepatitis B, C and/ or HIV infection.

Recent diagnosis or active treatment for malignancy.

Recent (within 3 weeks) severe allergy symptoms such as allergy-induced asthma, skin eruptions or urticaria.

Recent (within 3 weeks) viral or bacterial infections.

History of other immune abnormalities, or the presence of disease processes or medications that, in the opinion of the investigator, may alter immune function.

Pregnant and nursing females.

Women who have child-bearing potential but not using adequate birth control.

History of hypersensitivity reaction to sitagliptin.

History of anemia (based on the NIH laboratory department hemoglobin reference range for normal individuals).

History of pancreatitis

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00813228
090055, 09-DK-0055
Not Provided
Not Provided
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Not Provided
Principal Investigator: Kristin V Tarbell, Ph.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health Clinical Center (CC)
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP