Assessment of the Effects of a DPP-4 Inhibitor (Sitagliptin) Januvia on Immune Function in Healthy Individuals
| Status: | Completed |
|---|---|
| Conditions: | Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/6/2019 |
| Start Date: | December 18, 2008 |
| End Date: | June 17, 2011 |
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.
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.
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.
- 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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Click here to add this to my saved trials
