Liraglutide and Peripheral Artery Disease

Study Overview
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Brief Summary
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STARDUST is an open-label, two-arm randomized controlled trial, aimed at evaluating the effects of liraglutide on peripheral perfusion, as compared with the aggressive treatment of cardio-metabolic risk factors, in people with type 2 diabetes and peripheral artery disease. The potential benefits for participants in the study include the possibility of improving peripheral perfusion with drugs that have been evaluated as effective in controlling diabetes and safe and protective for cardiovascular health. The primary outcome of the study is the change of peripheral transcutaneous oxygen tension between groups at three and six months. Participants in the study will be followed for 6 months in order to evaluate the effects of liraglutide and the change of other secondary outcomes.

Official Title
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Effects of the Glucagon Like-peptide 1 (GLP-1) Receptor Agonist Liraglutide on Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: a Randomized Controlled Trial

Conditions
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Type 2 Diabetes, Peripheral Arterial Disease

Intervention / Treatment
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* Drug: Liraglutide
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of type 2 diabetes within at least 6 months peripheral arterial disease documented within al least 1 year by doppler ultrasound, angio-CT or arteriography peripheral transcutaneous oxygen pressure between 30 and 49 mmHg on anterior and/or posterior tibial arteries Hba1c 6,5-8% treatment of diabetes with metformin, insulin and/or sulfonylurea Exclusion Criteria: diagnosis of type 1 diabetes current treatment with GLP-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase -4 (DPP-4) inhibitors GLP-1RAs allergy or intolerance participation to other clinical studies history of pancreatitis, thyroid disease, diabetic gastroparesis or inflammatory bowel disease current or planned pregnancy acute myocardial infarction and/or acute cerebrovascular disease within 14 days from the screening visit planned revascularization procedure renal function with estimated glomerular filtration rate (eGFR) below 15 ml/min history of cancer and/or oncological treatment within 5 years from the screening visit current treatment with corticosteroids psychiatric or other clinical conditions which may interfere with the study

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide group<br>Patients in this arm will receive liraglutide, according to the current clinical practice. | Drug: Liraglutide<br>* Patients in this arm will receive one daily subcutaneous injection of liraglutide. The starting dose is 0.6 mg/dl per day. The dose has to be increased to 1.2 mg/dl per day after the first week of treatment and to 1.8 mg/dl after the second one.<br>* Other names: Intervention group;|
| Other: Control group<br>Patients in this arm will be strictly monitored with optimization of the therapy for atherosclerosis major risk factors. | Other: Control<br>* Patients in this arm will be strictly monitored for atherosclerosis major risk factors, such as hypertension and dyslipidemia, and treated according to current clinical practice.<br>* Other names: Control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral transcutaneous oxygen pressure | Change in transcutaneous oxygen pressure (mmHg) on anterior and posterior tibial arteries | 3 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Glucose control |  | 3 and 6 months | 
| Glucose control | fasting glucose differences between groups | 3 and 6 months | 
| Weight change |  | 3 and 6 months | 
| BMI change |  | 3 and 6 months | 
| Waist circumference change |  | 3 and 6 months | 
| Blood pressure change |  | 3 and 6 months | 
| Lipid profile | Difference between groups in total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides | 3 and 6 months | 
| Inflammation | Difference between groups in C reactive protein, fibrinogen, Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin (IL)-6 | 6 months | 
| Renal function | Difference between groups in creatininemia, uremia, albuminuria level | 3 and 6 months | 
| estimated glomerular filtration rate | Renal function | 3 and 6 months | 
| Angiogenesis | Difference between groups in endothelial progenitors cells circulating levels and vascular endothelial growth factor (VEGF) | 6 months | 
| Ankle-brachial Index (ABI) change | Difference between groups in ABI | 6 months | 
| Sexual hormonal profile | Difference between groups in sexual hormones levels [testosterone/estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), SHBG) | 6 months | 
| Male sexual function | Difference between groups in Erectile function (IIEF-5) | 6 months | 
| Female sexual function | Difference between groups in Female sexual function (FSFI) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes, Liraglutide, Transcutaneous Oxygen Tension, Peripheral arterial disease, Inflammation, Angiogenesis, Endothelial Dysfunction, Diabetic microvascular complications