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| Sponsor: | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00813228 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Diabetes Mellitus Type 1 Diabetes Mellitus Type 2 |
Drug: Sitagliptin (Januvia) |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study |
| Official Title: | Assessment of the Effects of a DPP-4 Inhibitor (Sitagliptin) Januvia on Immune Function in Healthy Individuals |
| Estimated Enrollment: | 40 |
| Study Start Date: | December 2008 |
| Estimated Study Completion Date: | October 2009 |
| Estimated Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Age greater than 18
Fasting blood glucose less than 100 mg/dl, and a normal Hgb A1c (less than 6.4%),
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).
Contacts and Locations| Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
| Contact: TTY | 1-866-411-1010 |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
More Information
| Study ID Numbers: | 090055, 09-DK-0055 |
| Study First Received: | December 19, 2008 |
| Last Updated: | November 25, 2009 |
| ClinicalTrials.gov Identifier: | NCT00813228 History of Changes |
| Health Authority: | United States: Federal Government |
|
Immune Function DDP-4 Sitagliptin GLP-1 TGF Beta |
|
Metabolic Diseases Autoimmune Diseases Immune System Diseases Molecular Mechanisms of Pharmacological Action Diabetes Mellitus Endocrine System Diseases Enzyme Inhibitors |
Pharmacologic Actions Sitagliptin Protease Inhibitors Dipeptidyl-Peptidase IV Inhibitors Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Glucose Metabolism Disorders |
