DiabetesPhase 4NCT01859793
Effects of Sitagliptin on Endothelial Function in Type 2 Diabetes on Background Metformin Therapy
A Phase 4 study testing sitagliptin in people with Diabetes and Atherosclerosis, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
The study is being performed to determine whether sitagliptin, a dipeptidyl peptidase-4 inhibitor, both acutely and chronically improves blood vessel function. Patients with type 2 diabetes who are on metformin will be enrolled in this study for up to 22 weeks in this double blinded cross over study where they will… Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Diabetes, Atherosclerosis
- What is being tested?
- sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Jul 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult age 21-70 years of age.
- Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.
- On stable metformin therapy for at least 6 weeks prior to enrollment.
- Glycosylated Hemoglobin ≥6.2% and ≤ 9.5%.
Who cannot join
- History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 50% on angiography or by confirmed history of myocardial infarction by standard criteria.)
- Evidence of other evident major illness including chronic renal insufficiency (creatinine clearance less than 60 mL/min),chronic liver disease (AST or ALT greater than 2.5 x normal), or cancer currently undergoing systemic therapy or had systemic therapy for cancer within 1 year of enrollment.
- Pregnancy as determined by urinary beta-HCG test
- Illicit drug use (heroin, cocaine etc) in the past 1 year.
- Alcohol abuse, defined as the equivalent of 14 beers/week for a man or 7 beers/week for a woman
- History of allergy to DPP-4 inhibitors at the time of screening/enrollment
Show all 10Show fewer
- Prior history of pancreatitis
- Patients currently on insulin or sulfonylurea therapy.
- Patients currently on digoxin.
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Trial locations and contacts
1 site in 1 country.
United States1 site
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: A Randomized, Crossover Design Study of Acute and Chronic Effects of Sitagliptin on Endothelial Function in Humans With Type 2 Diabetes on Background Metformin
The study is being performed to determine whether sitagliptin, a dipeptidyl peptidase-4 inhibitor, both acutely and chronically improves blood vessel function. Patients with type 2 diabetes who are on metformin will be enrolled in this study for up to 22 weeks in this double blinded cross over study where they will receive a sitagliptin pill once a day for 8 weeks and during a separate 8 weeks receive a matching placebo pill. The treatment periods are divided by a 4 week period. Blood vessel function will be measured by ultrasound before and after a single dose of sitagliptin and placebo, as well as after 8 weeks of treatment with each. Blood will also be taken to measure blood markers of inflammation at each time the ultrasounds are performed.
Read the detailed description
We plan to recruit 38 patients with T2DM for this single center, double blind randomized, interventional crossover trial comparing sitagliptin (100 mg/day) to matching placebo. We have chosen placebo over a comparator for this study as our goal is to determine whether sitagliptin both improves glycemic control and endothelial function, properties not shared by other popular classes of agents like sulfonylureas. Subjects will be randomized with a 1:1 allocation ratio to either sitagliptin 1st or placebo 1st.
The study have 5 total visits. Subjects who pass a phone screen will be invited to a screening visit for study eligibility (Visit 1) Informed consent will be reviewed; a unique study number will be assigned once written informed consent is obtained (no subject will be assigned more than 1 allocation number); relevant participant medical history will be recorded including currently prescribed medications; anthropometric measurements will be taken (height, weight, and waist circumference in metric units) and blood pressure will be recorded (measured in triplicate and averaged). Subjects will be allowed to take their blood pressure medication on the morning of their screening visit, but not the mornings of any of the other study visits to limit the acute influence of these medications on endothelial function. If the potential participant qualifies for the study, he/she will be randomized either to receive sitagliptin 1st (100 mg/day) or matching placebo. Prior to receiving either of set of pills, subjects will return to the study center within approximately 1-2 weeks of the screening visit to undergo initial tests of endothelial function and receive their pills. Prior to all study visits except screening, subjects will also be asked to refrain from any vigorous physical activity (no weight lifting, jogging or any activity vigorous than walking) 24 hours to reduce the risk of fasting hypoglycemia during the study visits. Subjects will also be asked to fast for 6-8 hours prior to the visit to limit the acute dietary influences on vascular endothelial function. At Visit 2, endothelial function will determined by brachial artery reactivity testing prior to and following a single dose of 100 mg of sitagliptin or matching placebo depending on the arm to which the subject was randomized. Blood samples will also be taken at this visit for systemic measurements of endothelial cell activation/inflammation (VCAM-1 and ICAM-1) prior to and 2 hours following acute drug administration. These will be measured at the indicated time points using commercially available kits.
Endothelial function, like the blood samples, will be measured just prior to medication administration and then 2 hours following medication administration by brachial artery reactivity testing as described in Section D.3. The 2 hour time from was chose in given the plasma levels of sitagliptin appear to peak 2 hours following dose administration.32 At the end of this visit, subjects will be given a 9 week supply of the study pills (sitagliptin or matching placebo) as dispensed by the Froedtert Hospital Investigational Pharmacy, and scheduled to return for Visit 3 approximately 8 weeks following Visit 2. Subjects will be asked to not take any study medication for the 24 hours prior to Visit 3. At Visit 3, subjects will undergo repeat testing of endothelial function. Following this study visit, subjects will remain off study pills until they return for Visit 4 approximately 4 weeks following Visit 3. Visit 4 repeats Visit 2 except subjects will receive the set of pills to which they had been randomized to receive second. Subjects will return to the study center for Visit 5 approximately 8 weeks after Visit 4. Visit 5 is identical to Visit 3. Subject adherence will be determined by pill counts performed by MCW Translational Research Unit nursing staff who will perform all pill accounting. All medication dispensation will be handled by the Froedtert Hospital Investigational Drug Pharmacy.
- Conditions
- Diabetes, Atherosclerosis
- Being tested
- sitagliptin, Placebo
- Keywords
- dipeptidyl peptidase-4 inhibitor, endothelium, vascular, diabetes type 2, nitric oxide, inflammation
- Medical subject headings
- Diabetes Mellitus, Atherosclerosis, Diabetes Mellitus, Type 2, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sitagliptinDrug
Also called Januvia
100 mg pill, administered once/day orally
PlaceboDrug
Matching placebo in appearance given once/day orally
| Study group | Role | What they receive |
|---|---|---|
| Matching Placebo | Placebo comparator | Matching Placebo for Sitagliptin Receives: Drug: Placebo |
| Sitagliptin | Active comparator | 100mg pill, PO administered once daily. Receives: Drug: sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brachial Artery Flow Mediated Dilation
A measurement of endothelial function in humans
Measured: Change before and after a single dose (2 hours post) and 8 weeks after daily dosing
Secondary outcomes (2)
Circulating Inflammatory Marker ICAM-1
Measured: Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication
Circulating Inflammatory Markers VCAM-1
Measured: Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2013 (estimated)
- Study startJun 2013
- Primary completionJan 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Michael E. Widlansky, Medical College of Wisconsin
- Investigators
- Michael E Widlansky, MD, MPH, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01859793
- Sponsor's protocol ID
- Merck-50600
- Status last verified
- Aug 2016
- First submitted
- 17 May 2013
- Last updated
- 21 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data set may be shared in a de-identified manner by request from qualified investigators with appropriate qualifications
Publications
Widlansky ME, Puppala VK, Suboc TM, Malik M, Branum A, Signorelli K, Wang J, Ying R, Tanner MJ, Tyagi S. Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy. Vasc Med. 2017 Jun;22(3):189-196. doi: 10.1177/1358863X16681486. Epub 2017 Feb 1.
PubMed 28145158
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Crossover Design Study of Acute and Chronic Effects of Sitagliptin on Endothelial Function in Humans With Type 2 Diabetes on Background Metformin
- ClinicalTrials.gov ID
- NCT01859793
- Acronym / sponsor ID
- Merck-50600
- Conditions
- Diabetes, Atherosclerosis
- Keywords
- dipeptidyl peptidase-4 inhibitor, endothelium, vascular, diabetes type 2, nitric oxide, inflammation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jun 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 22 May 2013 (estimated)
- Results
- Posted 21 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is being performed to determine whether sitagliptin, a dipeptidyl peptidase-4 inhibitor, both acutely and chronically improves blood vessel function. Patients with type 2 diabetes who are on metformin will be enrolled in this study for up to 22 weeks in this double blinded cross over study where they will receive a sitagliptin pill once a day for 8 weeks and during a separate 8 weeks receive a matching placebo pill. The treatment periods are divided by a 4 week period. Blood vessel function will be measured by ultrasound before and after a single dose of sitagliptin and placebo, as well as after 8 weeks of treatment with each. Blood will also be taken to measure blood markers of inflammation at each time the ultrasounds are performed.
Detailed description
We plan to recruit 38 patients with T2DM for this single center, double blind randomized, interventional crossover trial comparing sitagliptin (100 mg/day) to matching placebo. We have chosen placebo over a comparator for this study as our goal is to determine whether sitagliptin both improves glycemic control and endothelial function, properties not shared by other popular classes of agents like sulfonylureas. Subjects will be randomized with a 1:1 allocation ratio to either sitagliptin 1st or placebo 1st.
The study have 5 total visits. Subjects who pass a phone screen will be invited to a screening visit for study eligibility (Visit 1) Informed consent will be reviewed; a unique study number will be assigned once written informed consent is obtained (no subject will be assigned more than 1 allocation number); relevant participant medical history will be recorded including currently prescribed medications; anthropometric measurements will be taken (height, weight, and waist circumference in metric units) and blood pressure will be recorded (measured in triplicate and averaged). Subjects will be allowed to take their blood pressure medication on the morning of their screening visit, but not the mornings of any of the other study visits to limit the acute influence of these medications on endothelial function. If the potential participant qualifies for the study, he/she will be randomized either to receive sitagliptin 1st (100 mg/day) or matching placebo. Prior to receiving either of set of pills, subjects will return to the study center within approximately 1-2 weeks of the screening visit to undergo initial tests of endothelial function and receive their pills. Prior to all study visits except screening, subjects will also be asked to refrain from any vigorous physical activity (no weight lifting, jogging or any activity vigorous than walking) 24 hours to reduce the risk of fasting hypoglycemia during the study visits. Subjects will also be asked to fast for 6-8 hours prior to the visit to limit the acute dietary influences on vascular endothelial function. At Visit 2, endothelial function will determined by brachial artery reactivity testing prior to and following a single dose of 100 mg of sitagliptin or matching placebo depending on the arm to which the subject was randomized. Blood samples will also be taken at this visit for systemic measurements of endothelial cell activation/inflammation (VCAM-1 and ICAM-1) prior to and 2 hours following acute drug administration. These will be measured at the indicated time points using commercially available kits.
Endothelial function, like the blood samples, will be measured just prior to medication administration and then 2 hours following medication administration by brachial artery reactivity testing as described in Section D.3. The 2 hour time from was chose in given the plasma levels of sitagliptin appear to peak 2 hours following dose administration.32 At the end of this visit, subjects will be given a 9 week supply of the study pills (sitagliptin or matching placebo) as dispensed by the Froedtert Hospital Investigational Pharmacy, and scheduled to return for Visit 3 approximately 8 weeks following Visit 2. Subjects will be asked to not take any study medication for the 24 hours prior to Visit 3. At Visit 3, subjects will undergo repeat testing of endothelial function. Following this study visit, subjects will remain off study pills until they return for Visit 4 approximately 4 weeks following Visit 3. Visit 4 repeats Visit 2 except subjects will receive the set of pills to which they had been randomized to receive second. Subjects will return to the study center for Visit 5 approximately 8 weeks after Visit 4. Visit 5 is identical to Visit 3. Subject adherence will be determined by pill counts performed by MCW Translational Research Unit nursing staff who will perform all pill accounting. All medication dispensation will be handled by the Froedtert Hospital Investigational Drug Pharmacy.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Matching Placebo | Placebo comparator | Drug: PlaceboMatching Placebo for Sitagliptin |
| Sitagliptin | Active comparator | Drug: sitagliptin100mg pill, PO administered once daily. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult age 21-70 years of age.
- Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.
- On stable metformin therapy for at least 6 weeks prior to enrollment.
- Glycosylated Hemoglobin ≥6.2% and ≤ 9.5%.
Key exclusion criteria (10 listed)
- History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 50% on angiography or by confirmed history of myocardial infarction by standard criteria.)
- Evidence of other evident major illness including chronic renal insufficiency (creatinine clearance less than 60 mL/min),chronic liver disease (AST or ALT greater than 2.5 x normal), or cancer currently undergoing systemic therapy or had systemic therapy for cancer within 1 year of enrollment.
- Pregnancy as determined by urinary beta-HCG test
- Illicit drug use (heroin, cocaine etc) in the past 1 year.
- Alcohol abuse, defined as the equivalent of 14 beers/week for a man or 7 beers/week for a woman
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sitagliptinAlso: Januvia100 mg pill, administered once/day orally | Drug | Sitagliptin |
| PlaceboMatching placebo in appearance given once/day orally | Drug | Matching Placebo |
Primary outcome
Brachial Artery Flow Mediated Dilation
Time frame: Change before and after a single dose (2 hours post) and 8 weeks after daily dosing
A measurement of endothelial function in humans
2 secondary outcomes
Circulating Inflammatory Marker ICAM-1
Time frame: Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication
Circulating Inflammatory Markers VCAM-1
Time frame: Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28145158Widlansky ME, Puppala VK, Suboc TM, Malik M, Branum A, Signorelli K, Wang J, Ying R, Tanner MJ, Tyagi S. Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy. Vasc Med. 2017 Jun;22(3):189-196. doi: 10.1177/1358863X16681486. Epub 2017 Feb 1.
- Individual participant dataSharing planned: Yes. Data set may be shared in a de-identified manner by request from qualified investigators with appropriate qualifications
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael E Widlansky, MD, MPH principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sitagliptin in people with Diabetes and Atherosclerosis, run by Medical College of Wisconsin 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 10 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 21 Oct 2016. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Brachial Artery Flow Mediated Dilation (time frame: Change before and after a single dose (2 hours post) and 8 weeks after daily dosing). 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 NCT01859793, which also lists 1 linked publication.
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 21 Oct 2016.