AzTrials
AzTrials

Diabetes Mellitus Type 1Phase 1NCT00813228

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

A Phase 1 study testing Sitagliptin (Januvia) in people with Diabetes Mellitus Type 1 and Diabetes Mellitus Type 2, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
Sitagliptin (Januvia)
How many people
76 participants
Where
1 siteUnited States
Study dates
6 Jan 2009to 26 Nov 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.

Read the detailed description

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.

Being tested
Sitagliptin (Januvia)
Keywords
Immune Function, DDP-4, Sitagliptin, GLP-1, TGF Beta
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Camurati-Engelmann Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sitagliptin (Januvia)Drug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in plasma TGF-Beta 1 levels.

Secondary outcomes (1)
  1. Changes in plasma or stimulated PBMC cytokines levels, changes in stimulated PBMC proliferation, changes in peripheral blood gene expression and changes in immune phenotyping.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2008 (estimated)
  2. Study start6 Jan 2009
  3. Primary completion26 Nov 2019
  4. Study completion26 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Enrolment
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00813228
Sponsor's protocol ID
090055
Other IDs
09-DK-0055
Status last verified
26 Nov 2019
First submitted
19 Dec 2008
Last updated
29 Nov 2019
Results posted
No

Publications

  • Drucker DJ. Glucagon-like peptide-1 and the islet beta-cell: augmentation of cell proliferation and inhibition of apoptosis. Endocrinology. 2003 Dec;144(12):5145-8. doi: 10.1210/en.2003-1147. No abstract available.

    PubMed 14645210
  • Thompson MA, Ohnuma K, Abe M, Morimoto C, Dang NH. CD26/dipeptidyl peptidase IV as a novel therapeutic target for cancer and immune disorders. Mini Rev Med Chem. 2007 Mar;7(3):253-73. doi: 10.2174/138955707780059853.

    PubMed 17346218
  • Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007 Jul 11;298(2):194-206. doi: 10.1001/jama.298.2.194.

    PubMed 17622601

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sitagliptin (Januvia) in people with Diabetes Mellitus Type 1 and Diabetes Mellitus Type 2, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in plasma TGF-Beta 1 levels.. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00813228, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in