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

Differences in Endothelial Function Amongst Sitagliptin and Liraglutide Users: A Randomized, Open-label, Parallel-group and Active Controlled Trial

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

Study Overview

• Status: Completed
• Conditions: DIABETES Mellitus Type 2 Not Well Controlled
• Intervention / Treatment: Drug: Liraglutide; Drug: Sitagliptin

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Januvia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the effects on endothelial function of a three month treatment with Liraglutide compared to Sitagliptin.	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.	3months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Anna Cruceta
• Investigators: Principal Investigator: Antonio Ceriello, MD, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: January 7, 2013
• First Submitted That Met QC Criteria: February 4, 2013
• First Posted (ESTIMATE): February 6, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): September 15, 2015
• Last Update Submitted That Met QC Criteria: September 14, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: DIABETES Mellitus Type 2; Difficult control
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Liraglutide; Sitagliptin Phosphate
• Other Study ID Numbers: LAED001