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Type 2 Diabetes MellitusPhase 4NCT02380521

Exenatide Once Weekly, Cardiovascular Risk and Type-2 Diabetes

A Phase 4 study testing Exenatide once weekly (BYDUREON™) in people with Type 2 Diabetes Mellitus, run by University of Palermo at 1 site in Italy.

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

The glucagon-like peptide 1 (GLP-1) agonist exenatide represents an effective therapy in patients with type 2 diabetes mellitus (T2DM), which also seems to have some important non-glycemic effects. Yet, these non-glycemic effects are still largely unknown. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
Exenatide once weekly (BYDUREON™)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteItaly
Study dates
Jan 2015to Nov 2016
Phase
Phase 4
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of informed consent prior to any study specific procedures;
  • Men and women with T2DM aged >18 years;
  • BMI >25 kg/m2;
  • HbA1c 7.5-8.5 %;
  • Receiving metformin therapy (doses ranging from 1500 to 3000 mg daily) for at least 8 weeks.

Who cannot join

  • Pregnancy or willingness to become pregnant;
  • Moderate and severe liver dysfunction;
  • Moderate and severe renal failure;
  • Previous major cardiovascular event;
  • Severe infections at the discretion of the investigator (such as human immunodeficiency virus [HIV], hepatitis B virus [HBV] and hepatitis C virus [HCV]);
  • Any malignancy;
  • Plasma triglycerides >400 mg/dL, plasma LDL-cholesterol > 250 mg/dL.

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • University Hospital of Palermo

    Palermo, 90127

Other trials in Italy

About this study

Official title: Effect of Exenatide Once Weekly on Cardiovascular Risk Markers in Patients With Type-2 Diabetes

The glucagon-like peptide 1 (GLP-1) agonist exenatide represents an effective therapy in patients with type 2 diabetes mellitus (T2DM), which also seems to have some important non-glycemic effects. Yet, these non-glycemic effects are still largely unknown.

The effect of exenatide once weekly was investigated in controlled, blinded and open-label clinical studies in subjects with T2DM who were controlled on diet and exercise alone or in combination with oral antidiabetic agents, but also in multi-dose controlled studies and such studies resulted in significant reductions in glycemic parameters (mean glycated hemoglobin (HbA1c), fasting serum/plasma glucose as well as postprandial plasma glucose levels), but also in body weight, over 24 to 30 weeks. Meaningful reductions were observed as early as week 4 of treatment, and maintained through 6 years of treatment.

Read more

The study investigating cardiovascular effects of exenatide once weekly is currently undergoing. The results available are not numerous (such as DURATION-2, DURATION-3, DURATION-4 studies) and cannot lead to definitive conclusions.

In this study the investigators will evaluate the effect of exenatide once-weekly on multiple cardiovascular risk markers. These markers are related to subclinical atherosclerosis, endothelial dysfunction, oxidative stress and atherogenic lipoproteins.

The investigators will perform an open label, single-arm, prospective, intervention study using exenatide once weekly for a period of 8 months on 60 patients with T2DM.

Read the detailed description

The research hypothesis is to assess whether exenatide once weekly can reduce subclinical atherosclerosis (as measured by carotid-intima media thickness [cIMT]) in patients with T2DM.

The primary objective is to assess whether exenatide once weekly can reduce subclinical atherosclerosis (as measured by cIMT) in patients with T2DM.

Primary endpoint: Reduction in cIMT. The secondary objective is to assess whether exenatide once weekly can reduce atherogenic lipoproteins, oxidative stress and endothelial dysfunction in patients with T2DM.

Secondary endpoint: Reduction in atherogenic lipoproteins, oxidative stress and improvement of endothelial dysfunction.

The purpose of the present 8 months study is to elucidate largely unknown non-glycemic effects of exenatide as add-on to metformin, including effects on cIMT, oxidative stress parameters and atherogenic lipoproteins, in addition to its benefit on glycemic control, weight loss and other efficacy parameters, as well as the safety profile of exenatide.

The data for clinical and biochemical analyses, including collection of efficacy variables, ECG, pulse and physical examination, will be collected at baseline and after 8 months of therapy (at 6 months of the treatment, only the routine laboratory analyses, including HbA1c, will be performed).

Clinical diagnostic tools will include the measurement of:

  1. cIMT, that will be assessed by B-mode real-time ultrasound using a single sonographer (Medison SonoAce Pico, with a probe of 7.5-10.0 MHz) in a standardized manner with fixed angles of insonation;
  2. Endothelial dysfunction, that will be assessed by flow mediated dilation of brachial artery.

Biochemical analyses will include the analysis of:

  1. Routine testing: blood testing, liver and kidney profile, plasma lipids, glucose metabolism parameters;
  2. Oxidative stress parameters (plasma glutathione, serum lipid hydroperoxides, reactive oxygen species);
  3. Atherogenic lipoproteins, e.g. the analysis of 11 distinct lipoproteins including very-low-density lipoprotein (VLDL), 3 intermediate density lipoprotein (IDL) subclasses and 7 low density lipoprotein (LDL) subclasses.
Being tested
Exenatide once weekly (BYDUREON™)
Keywords
Exenatide once weekly, T2DM, IMT, Atherogenic lipoproteins
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.

  • Exenatide once weekly (BYDUREON™)Drug

    Also called BYDUREON™

    Exenatide is considered investigational medicinal product (IMP) and will be prescribed to enrolled patients in accordance with local requirements.

    Exenatide will be available at a fixed dose of 2 mg and supplied as a kit. Exenatide should be injected subcutaneously (SC) in the thigh, upper arm (deltoid region) or abdomen. The injection site does not have to be consistent throughout the study. Injection can be done at any time of the day irrespective of meals. It is recommended that the time of injection is consistent throughout the study. Subjects will be instructed to perform an air shot before the first injection.

    Subjects will follow a fixed dose of 2 mg

Study groups in NCT02380521
Study groupRoleWhat they receive
60 patients with T2DMExperimentalThese patients will be treated with exenatide once weekly for a period of 8 months
Receives: Drug: Exenatide once weekly (BYDUREON™)

What is being measured

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

  1. Subclinical atherosclerosis (as measured by cIMT) in patients with T2DM treated with exenatide once weekly

    Reduction in cIMT after 8 months of the treatment

    Measured: Change from baseline to 8 months of the treatment

Secondary outcomes (3)
  1. Atherogenic lipoproteins (as measured by the analysis of 11 distinct lipoprotein subclasses using the Lipoprint system®) in patients with T2DM treated with exenatide once weekly

    Reduction in atherogenic lipoproteins including small dense LDL particles after 8 months of the treatment

    Measured: Change from baseline to 8 months of the treatment

  2. Oxidative stress (as measured by markers of oxidative stress) in patients with T2DM treated with exenatide once weekly

    Reduction in oxidative stress after 8 months of the treatment

    Measured: Change from baseline to 8 months of the treatment

  3. Endothelial dysfunction (as measured by flow mediated dilation of brachial artery) in patients with T2DM treated with exenatide once weekly

    Improvement of endothelial dysfunction as indicated by changes in flow mediated dilation of brachial artery after 8 months of the treatment

    Measured: Change from baseline to 8 months of the treatment

Timeline

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

  1. First posted5 Mar 2015 (estimated)
  2. Study startJan 2015
  3. Primary completionJul 2016
  4. Study completionNov 2016

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 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02380521
Sponsor's protocol ID
ESR-14-10139
Status last verified
Nov 2016
First submitted
15 Feb 2015
Last updated
8 Nov 2016
Results posted
No
Data monitoring committee
No

Publications

  • Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, Porter L; DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008 Oct 4;372(9645):1240-50. doi: 10.1016/S0140-6736(08)61206-4. Epub 2008 Sep 7.

    PubMed 18782641
  • Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE; DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010 Aug 7;376(9739):431-9. doi: 10.1016/S0140-6736(10)60590-9. Epub 2010 Jun 26.

    PubMed 20580422
  • Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010 Jun 26;375(9733):2234-43. doi: 10.1016/S0140-6736(10)60406-0.

    PubMed 20609969
  • Russell-Jones D, Cuddihy RM, Hanefeld M, Kumar A, Gonzalez JG, Chan M, Wolka AM, Boardman MK; DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care. 2012 Feb;35(2):252-8. doi: 10.2337/dc11-1107. Epub 2011 Dec 30.

    PubMed 22210563
  • Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, Trautmann M, Porter L. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011 May;96(5):1301-10. doi: 10.1210/jc.2010-2081. Epub 2011 Feb 9.

    PubMed 21307137
  • Buse JB, Nauck M, Forst T, Sheu WH, Shenouda SK, Heilmann CR, Hoogwerf BJ, Gao A, Boardman MK, Fineman M, Porter L, Schernthaner G. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013 Jan 12;381(9861):117-24. doi: 10.1016/S0140-6736(12)61267-7. Epub 2012 Nov 7.

    PubMed 23141817

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Exenatide once weekly (BYDUREON™) in people with Type 2 Diabetes Mellitus, run by University of Palermo at 1 site in Italy.

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 7 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 8 Nov 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 Italy. 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 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?

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?

Subclinical atherosclerosis (as measured by cIMT) in patients with T2DM treated with exenatide once weekly (time frame: Change from baseline to 8 months of the treatment). 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 NCT02380521, which also lists 6 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 8 Nov 2016.

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