Differences in Endothelial Function Amongst Sitagliptin and Liraglutide Users (LAED001)

• ClinicalTrials.gov Identifier: NCT01785043
• Recruitment Status: Completed
• First Posted: February 6, 2013
• Last Update Posted: September 15, 2015
• Sponsor: Anna Cruceta
• Information provided by (Responsible Party): Anna Cruceta, Fundacion Clinic per a la Recerca Biomédica

Study Description

Brief Summary:

Differences in endothelial function amongst Sitagliptin and Liraglutide Users. A randomized, open-label, parallel-group and active controlled trial

Condition or disease	Intervention/treatment	Phase
DIABETES Mellitus Type 2 Not Well Controlled	Drug: Liraglutide; Drug: Sitagliptin	Phase 4

Detailed Description:

Randomized, open-label, parallel-group, active controlled, phase IV study to assess the efficacy and safety of a 3 month treatment period with Liraglutide to Sitagliptin in type 2 diabetes patients not well controlled at the maximum tolerated dose of metformin.The study has been designed with a random design as it is one of the most important techniques for avoiding bias in clinical trials. The study will follow a parallel group, open-label design as liraglutide is administered by subcutaneous injection and sitagliptin orally in tablets. A double-dummy design has been rejected because it is highly complicated in a phase IV study, and any bias of an open-label design has a lower impact on objective variables (as it is our primary endpoint) and it could be compensated with the proposed random design.Sitagliptin has been selected as the active control as it is one of the prescribed treatments for type 2 diabetes patients not well controlled at the maximum tolerated dose of metformin.

The study objectives will be assessed after 3 months of therapy as it is considered a suitable timing for identifying short-term changes on flow-mediated vasodilation

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Differences in Endothelial Function Amongst Sitagliptin and Liraglutide Users: A Randomized, Open-label, Parallel-group and Active Controlled Trial
• Study Start Date: March 2013
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: September 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Liraglutide; Liraglutide will be administered once a day by subcutaneous injection (under the skin) in the abdomen, thigh, or upper arm. It will be given independently of meals and preferably at the same each day. The starting dose will be 0.6 mg. After one week, the dose will be increased to 1.2 mg, and then it will be increased to 1.8 mg one week later to achieve better control of blood glucose. When Liraglutide is added to existing treatment containing metformin, as it is our scenario, the dose of metformin does not have to be changed.	Drug: Liraglutide; Liraglutide is available if pre-filled pens (6 mg/ml) as a solution for injection (Victoza®). One ml of solution contains 6 mg of Liraglutide (human glucagon-like peptide-1 analogue produced by recombinant DNA technology in Saccharomyces cerevisiae). One pre-filled pen contains 18 mg Liraglutide in 3 ml.; Other Name: Victoza®
Active Comparator: Sitagliptin; Sitagliptin will be administered once daily at a 100 mg dose. When Sitagliptin is used in combination with metformin, as it is our scenario, the dose of metformin should be maintained. If a dose of Sitagliptin is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day. Sitagliptin will be used daily during the study period of 12 weeks.	Drug: Sitagliptin; Sitagliptin is available in 100 mg film-coated tablets (Januvia®). Each tablet contains sitagliptin phosphate monohydrate, equivalent to 100 mg sitagliptin.; Other Name: Januvia

Outcome Measures

Primary Outcome Measures :

1. Assess the effects on endothelial function of a three month treatment with Liraglutide compared to Sitagliptin. [ Time Frame: 3months ]
   The primary objective is to assess the effects on endothelial function of a three month treatment with Liraglutide compared to Sitagliptin, assessed as the baseline corrected change in endothelial function by flow-mediated vasodilation (FMD) of the brachial artery at 3 months.

Secondary Outcome Measures :

1. The evaluation of other emerging potential cardiovascular risk factors [ Time Frame: 3months ]
   1. Secondary objectives will include the evaluation of other emerging potential cardiovascular risk factors, such as oxidative stress markers, cytokines, and soluble cell adhesion molecules.
   2. The safety profile of both treatment groups will be also evaluated.

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
2. Male or female patients between 45 and 65 years old
3. Pre-existing type 2 diabetes with HbA1c between 7.0 and 9.5%
4. Triglycerides >1.68 mmol/L
5. HDL cholesterol <1.29 mmol/L in women and <1.04 mmol/L in men
6. Systolic blood pressure (SBP) <130 mmHg and diastolic blood pressure (DBP) <85 mmHg or treatment with antihypertensive agents

Exclusion Criteria:

1. Known or suspected hypersensitivity to trial product(s) or related products
2. Previous participation in this trial. Participation is defined as being randomised.
3. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive, or males who are sexually active and not surgically sterilised, who or whose partner are not using adequate contraception
4. Moderate or severe renal dysfunction (creatinine clearance <60 ml/min)
5. Previous type 2 diabetes treatment apart from metformin or insulin
6. Current smoker or history of smoking within 6 months prior to screening.
7. Evidence of overt cardiovascular disease, (documented coronary heart disease, class II-IV congestive heart failure, cerebrovascular disease, or peripheral vascular disease).
8. Caffeine intake within 24 hours of endothelial function measurements.
9. Use of any drug with known clinically significant sympathetic or parasympathetic effects, as determined by the Investigator.
10. Initiation or change (dose or treatment regimen) in concomitant blood pressure-lowering medication within 4 weeks prior to screening and throughout the day.
11. The receipt of any investigational medicinal product within 6 months prior to screening.
12. Presence of cancer or other significant medical condition
13. Inability to follow verbal or written instructions

Contacts and Locations

Locations

Spain

Hospital Clínic de Barcelona

Barcelona, Spain, 08036

Sponsors and Collaborators

Anna Cruceta

Investigators

• Principal Investigator: Antonio Ceriello, MD; Hospital Clinic of Barcelona

More Information

• Responsible Party: Anna Cruceta, Project manager Clinical Trials Unit, Fundacion Clinic per a la Recerca Biomédica
• ClinicalTrials.gov Identifier: NCT01785043
• Other Study ID Numbers: LAED001
• First Posted: February 6, 2013
• Last Update Posted: September 15, 2015
• Last Verified: September 2015

Keywords provided by Anna Cruceta, Fundacion Clinic per a la Recerca Biomédica:

DIABETES Mellitus Type 2; Difficult control

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sitagliptin Phosphate; Liraglutide; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action