Type 2 DiabetesPhase 4NCT02024477

Effect of Saxagliptin on EPCs as a Cellular Biomarker for Evaluating Endothelial Dysfunction in Early T2DM Patients

A Phase 4 study testing Saxagliptin in people with Type 2 Diabetes, run by George Washington University 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

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Trial summary

Who is it for?: Ages 40 to 70 years
Conditions the study is for: Type 2 Diabetes
What is being tested?: Saxagliptin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 42 participants
Where: 1 siteUnited States
Study dates: Nov 2013to Dec 2017
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 40 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adults aged 40-70 years.
Diagnosis of type 2 diabetes within the previous 8 years using criteria of the American Diabetes Association
Currently treated with no hypoglycemic agents other than a stable dose (>3 months) of metformin (≥1.0 to ≤2 grams daily).
HbA1C between 6 to 9% (both inclusive)
BMI 25 to 39.9 kg/m2 (both inclusive)

Who cannot join

Contraindications for moderate exercise
Implanted devices (e.g., pacemakers) that may interact with Tanita scale
Previous coronary or cerebrovascular event within 6 months of screening or active or clinically significant coronary and/or peripheral vascular disease.
Low hematocrit <28 Units
Pre-existing liver disease and/or ALT and AST >2.5X's UNL
Kidney disease (serum creatinine levels ≥1.5 mg/dL for men, ≥1.4 mg/dL for women,Creatinine Clearance ≤50 mL/min)

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History of pancreatitis, or cancer (except basal cell carcinoma)
Statin use started (or dose change) in the last 3 months.
Use of oral or injectable anti-diabetic medication other than Metformin
Use of any form of consistent-long term steroid medication (oral, inhaled injected or nasal) within the last 3 months
Systolic BP> 140 mmHg and diastolic BP> 90 mmHg
Active wounds or recent surgery within 3 months.
Inflammatory disease, or current use of anti-inflammatory drugs
triglycerides >400 mg/dL
untreated hyper/hypothyroidism Additionally, patients who are active smokers, patients who are pregnant, nursing women, and post menopausal women who are on hormone replacement therapy will be excluded.
Patients on low dose oral contraceptives will be allowed to participate as these formulations contain lesser amount of estrogens.

Trial locations and contacts

1 site in 1 country.

United States1 site

Medical Faculty Associates Inc
Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: Effect of Saxagliptin (DPP-4 Inhibitor) on Endothelial Progenitor Cells (EPCs) as a Cellular Biomarker for Evaluating Endothelial Dysfunction in Early Type 2 Diabetes Patients

Type 2 diabetes is a national epidemic. Diabetes has undesirable effects on blood vessels which may contribute to heart disease. Endothelial Progenitor Cells(EPCs) are found in the blood . Research has shown that improving the survival of these special blood cells may decrease the harmful effects of diabetes on blood vessels and reduce or reverse heart disease. Saxagliptin is an FDA(Food and Drug Administration) approved prescription medicine used along with diet and exercise to lower blood sugar in people with Type 2 diabetes. It is in a class of diabetes medication called DPP-4 inhibitors. DPP-4 inhibitors have been shown to increase EPCs in patients with Type 2 diabetes.

Hypothesis: We believe poor viability and function of EPCs in early diabetes ultimately affects the repair and regeneration of the endothelium and that prompt intervention using saxagliptin with another oral hypoglycemic agent, Metformin, may reduce or reverse cardiovascular risk by improving EPC survival and function above and beyond adequate glucose metabolism control.

Read the detailed description

Type 2 diabetes is a national epidemic 1,2 with significant macro and microvascular complications. Insulin resistance in prediabetes and early and late diabetes are associated with endothelial dysfunction.

A few studies indicate that EPCs can act as a suitable bio-marker for monitoring cardiovascular morbidity. In this proposal we suggest that EPCs or CD34 positive cells can act as a suitable cellular biomarker for estimating and following endothelial dysfunction in early type 2 diabetes patients.

EPCs have been used as a regenerative tool in ischemic myocardium and diabetic wound healing. Endothelial dysfunction with associated inflammation may be a consequence of excess super-oxide presence in a setting of diabetes which is a pro-oxidative stress condition causing EPC dysfunction and senescence. Therefore monitoring EPC number, function and gene expression may serve as a very useful cellular bio-marker for cardiovascular complications in early type 2 diabetes.

Though lifestyle modification has been proposed as a main stay for prevention and treatment of early type 2 diabetes, several new therapies for diabetes have been developed in recent years. Incretins and incretin mimetics appear to hold promise. Oral DPP-4 inhibitors have been shown to increase EPCs in patients with type 2 diabetes reportedly via SDF-1 alpha up-regulation. Interestingly, up-regulation of SDF-1 alpha and vascular endothelial growth factor (VEGF), both chemotactic factors increase mobilization and recruitment of EPCs in the face of acute ischemic injury for repair and regeneration.

Several studies have shown positive effect of incretins (Glucagon like peptide, GLP-1) and incretin receptor agonists (GLP-1 receptor agonists) on cardiovascular risk factors in type 2 diabetes patients and even in patients with chronic heart failure and left ventricular dysfunction who do not have diabetes.

DPP-4 Inhibitors may have cardio-protective effects of their own, as they increase bio-availability of endogenous GLP-1. They improve blood flow and nitric oxide production in endothelium. These are unique properties not demonstrated by other oral diabetes medications. The mechanism underlying these effects may be mediated by increased nitric oxide bioavailability but is not completely known. It is possible that Saxagliptin, a member of DPP-4 inhibitor group of drugs may be able to improve number and function of CD34+ endothelial progenitor cells by up-regulating chemotactic agent SDF1 alpha (DPP-4 degrades SDF-1) and its receptor CXCR47, 20, 21, 30, 31.

Poor viability and function of EPCs in early diabetes may ultimately affect the repair and regeneration of the endothelium and prompt intervention may reduce or reverse cardiovascular risk by improving EPC survival and function above and beyond adequate glucose metabolism control.

Therefore we would like to explore the effect of saxagliptin in addition to lifestyle intervention, on number and function and gene expression of EPC and impact on endothelial dysfunction in type 2 diabetes.

Conditions: Type 2 Diabetes
Being tested: Saxagliptin, Placebo
Keywords: endothelial cells, cellular biomarker, endothelial dysfunction
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

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

SaxagliptinDrug
Also called Onglyza
5 mg tablet once daily for 12 weeks
PlaceboDrug
1 tablet daily for 12 weeks

Study groups in NCT02024477
Study group	Role	What they receive
Placebo	Placebo comparator	Matching placebo 1 pill daily for 12 weeks Receives: Drug: Placebo
saxagliptin	Active comparator	Saxagliptin 5mg once daily for 12 weeks Receives: Drug: Saxagliptin

What is being measured

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

CD34+ Endothelial Progenitor Cells Number
We will use patient's peripheral blood derived CD34+ cells looking at number of CD34+ Endothelial Progenitor Cell as % of the total Mononuclear cell population. Post saxagliptin will be compared to pre saxagliptin measurement
Measured: Up to 12 weeks post saxagliptin
CD 34+ Cell Function
function of EPC cell as migration of CD34+ cells in response to SDF-1a ( 100 ng/mL). Results are expressed in fluorescence ratio between cells exposed to the chemotactic factor and cells exposed to chemo attractant-free media ( control) followed by lysis in presence of CyQuant GR dye.
Measured: Up to 12 weeks post saxagliptin Up to 12 weeks post saxagliptin: Visit 1 at Baseline, Visit 2 at 6 weeks, and Visit 3 at 12 weeks

Secondary outcomes (5)

Serum Endothelial Inflammatory Marker hsCRP
Measured: Baseline 6 and 12 weeks post saxagliptin
Fasting Lipid Profile LDL/HDL
ratio of LDL over HDL
Measured: Baseline, 6 and 12 weeks post saxagliptin
Glycemic Control
measuring HbA1c levels
Measured: Baseline, 6 and 12 weeks post saxagliptin
Adiposity
measured using a Tanita Body Composition Fat Analyzer scale, measured as percentage body fat
Measured: Baseline, 6 and 12 weeks post saxagliptin
Arterial Stiffness
Arterial stiffness assessed using Vascular Flow and wave measurement equipment, SphygmoCor CP system from ATCOR. Reported as Augmentation Index adjusted for a heart rate of 75. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. Lower the value, better correlated outcome as positive augmentation represents stiffer artery.
Measured: Baseline, 6 and 12 weeks post saxagliptin

Timeline

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

Nov 2013Dec 2017

First posted31 Dec 2013 (estimated)
Study startNov 2013
Primary completionSep 2017
Study completionDec 2017

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 Type 2 DiabetesStudies of the same condition, open and under way.
More trials run by George Washington UniversityThe 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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02024477
Sponsor's protocol ID: CV181-305
Status last verified: Jan 2019
First submitted: 13 Dec 2013
Last updated: 15 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No: There is no current plan for sharing IPD with other researchers.

Publications

Dore FJ, Domingues CC, Ahmadi N, Kundu N, Kropotova Y, Houston S, Rouphael C, Mammadova A, Witkin L, Khiyami A, Amdur RL, Sen S. The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial. Cardiovasc Diabetol. 2018 May 3;17(1):65. doi: 10.1186/s12933-018-0709-9.
PubMed 29724198

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Saxagliptin (DPP-4 Inhibitor) on Endothelial Progenitor Cells (EPCs) as a Cellular Biomarker for Evaluating Endothelial Dysfunction in Early Type 2 Diabetes Patients
ClinicalTrials.gov ID: NCT02024477
Acronym / sponsor ID: CV181-305
Conditions: Type 2 Diabetes
Keywords: endothelial cells, cellular biomarker, endothelial dysfunction
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: George Washington UniversityUniversity, hospital or other
Collaborators: AstraZeneca
Study start: Nov 2013
Primary completion: Sep 2017 (actual)
Study completion: Dec 2017 (actual)
First posted: 31 Dec 2013 (estimated)
Results: Posted 29 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboMatching placebo 1 pill daily for 12 weeks
saxagliptin	Active comparator	Drug: SaxagliptinSaxagliptin 5mg once daily for 12 weeks

Who may qualify

Ages: 40 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Adults aged 40-70 years.
Diagnosis of type 2 diabetes within the previous 8 years using criteria of the American Diabetes Association
Currently treated with no hypoglycemic agents other than a stable dose (>3 months) of metformin (≥1.0 to ≤2 grams daily).
HbA1C between 6 to 9% (both inclusive)
BMI 25 to 39.9 kg/m2 (both inclusive)

Key exclusion criteria (16 listed)

Contraindications for moderate exercise
Implanted devices (e.g., pacemakers) that may interact with Tanita scale
Previous coronary or cerebrovascular event within 6 months of screening or active or clinically significant coronary and/or peripheral vascular disease.
Low hematocrit <28 Units
Pre-existing liver disease and/or ALT and AST >2.5X's UNL

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
SaxagliptinAlso: Onglyza5 mg tablet once daily for 12 weeks	Drug	saxagliptin
Placebo1 tablet daily for 12 weeks	Drug	Placebo

Primary outcome

CD34+ Endothelial Progenitor Cells Number
Time frame: Up to 12 weeks post saxagliptin
We will use patient's peripheral blood derived CD34+ cells looking at number of CD34+ Endothelial Progenitor Cell as % of the total Mononuclear cell population. Post saxagliptin will be compared to pre saxagliptin measurement
CD 34+ Cell Function
Time frame: Up to 12 weeks post saxagliptin Up to 12 weeks post saxagliptin: Visit 1 at Baseline, Visit 2 at 6 weeks, and Visit 3 at 12 weeks
function of EPC cell as migration of CD34+ cells in response to SDF-1a ( 100 ng/mL). Results are expressed in fluorescence ratio between cells exposed to the chemotactic factor and cells exposed to chemo attractant-free media ( control) followed by lysis in presence of CyQuant GR dye.

5 secondary outcomes

Serum Endothelial Inflammatory Marker hsCRP
Time frame: Baseline 6 and 12 weeks post saxagliptin
Fasting Lipid Profile LDL/HDL
Time frame: Baseline, 6 and 12 weeks post saxagliptin
Glycemic Control
Time frame: Baseline, 6 and 12 weeks post saxagliptin
Adiposity
Time frame: Baseline, 6 and 12 weeks post saxagliptin
Arterial Stiffness
Time frame: Baseline, 6 and 12 weeks post saxagliptin

Results and safety

Results posted to the registry on 29 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	21	21
Saxagliptin	21	21

Primary outcome: CD34+ Endothelial Progenitor Cells Number

Time frame: Up to 12 weeks post saxagliptin. Mean (Standard Deviation). Unit: % of Mononuclear Cells

Measure	Placebo n = 21	Saxagliptin n = 21
Value	2.0 (0.3)	2.8 (0.5)

Primary outcome: CD 34+ Cell Function

Time frame: Up to 12 weeks post saxagliptin Up to 12 weeks post saxagliptin: Visit 1 at Baseline, Visit 2 at 6 weeks, and Visit 3 at 12 weeks. Mean (Standard Deviation). Unit: Ratio

Measure	Placebo n = 21	Saxagliptin n = 21
Visit 1 - Week 0	1.2 (0.1)	1.05 (0.06)
Visit 2 - Week 6	1.05 (0.15)	1.55 (0.2)
Visit 3 - Week 12	1.0 (0.06)	1.2 (0.05)

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 20 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 21 (4.8%)	0 of 21 (0%)	0 of 21
Saxagliptin	1 of 21 (4.8%)	0 of 21 (0%)	0 of 21

Limitations and caveats (from the sponsor): Limitations of our study may include the relatively short duration of 12 week Saxagliptin therapy, which may have been inadequate to see significant changes in certain clinical and cellular parameters.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29724198Dore FJ, Domingues CC, Ahmadi N, Kundu N, Kropotova Y, Houston S, Rouphael C, Mammadova A, Witkin L, Khiyami A, Amdur RL, Sen S. The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial. Cardiovasc Diabetol. 2018 May 3;17(1):65. doi: 10.1186/s12933-018-0709-9.
Individual participant dataSharing planned: No. There is no current plan for sharing IPD with other researchers.

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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.

Sabyaschi Sen, PhD, MD principal investigator

George Washington University

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 Saxagliptin in people with Type 2 Diabetes, run by George Washington University 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 5 inclusion and 16 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 15 Feb 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. 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 29 Jan 2019). 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?

CD34+ Endothelial Progenitor Cells Number (time frame: Up to 12 weeks post saxagliptin). The study lists 2 primary outcomes in all. 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 NCT02024477, 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 15 Feb 2019.