To Evaluate the Effect of Liraglutide on Ambulatory Blood Pressure-A Pilot Study

Study Overview
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Brief Summary
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The investigators are conducting this research to study the effect of Liraglutide on blood pressure. Several studies have shown increased cardiovascular complications and deaths in diabetics with hypertension. The importance of blood pressure control in diabetes has been shown in many clinical trials. No drug already approved for treating Type 2 Diabetes Mellitus is known to reduce blood pressure along with improving diabetes. However, prior research studies with liraglutide have suggested that treatment with liraglutide improves blood pressure. This effect is seen very quickly and even prior to any weight loss. The mechanism behind this effect is yet to be determined.

Detailed Description
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The investigators are conducting this research to study the effect of Liraglutide on blood pressure. Several studies have shown increased cardiovascular complications and deaths in diabetics with hypertension. The importance of blood pressure control in diabetes has been shown in many clinical trials. No drug already approved for treating Type 2 Diabetes Mellitus is known to reduce blood pressure along with improving diabetes. However, prior research studies with liraglutide have suggested that treatment with liraglutide improves blood pressure. This effect is seen very quickly and even prior to any weight loss. The mechanism behind this effect is yet to be determined. Blood pressure will be monitored using the 24 hour Ambulatory Blood Pressure monitor: a device that monitors your blood pressure while you continue normal activity. We have chosen this method to monitor blood pressure because most of the prior studies have proven it to be superior over a single blood pressure recording and its ability to better predict clinical outcomes. It is well known that both diabetes and hypertension cause endothelial dysfunction. Endothelium is the inner lining of the blood vessels. When it is functioning, it is supposed to regulate blood clotting, help with the body's immune response, controls the volume of fluid and other substances that pass through the blood vessels. Hence, normal endothelial function protects the blood vessels from atherosclerosis (hardening) and builds up of plaque. When it is not functioning well (as in diabetes, hypertension, cigarette smokers etc.) it does not perform one or more of these functions. Hence, in this study, we will also measure the endothelial function using a machine: ENDO PAT. This is a non-invasive diagnostic test which is done in the doctor's office. Usually takes about 15 minutes. It is not painful. It generates an EndoScore which indicates the current state of the endothelial health. This is a PILOT study (a small-scale study designed to determine if a larger, full-scale study is doable) to prove this effect which if proven will be extended to a larger, multicenter trial. Of note: Liraglutide has already been approved for treating Type 2 Diabetes Mellitus.

Official Title
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To Evaluate the Effect of Liraglutide on Ambulatory Blood Pressure-A Pilot Study

Conditions
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Diabetes Mellitus, Non-Insulin-Dependent, Hypertensive Disease

Intervention / Treatment
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* Drug: Liraglutide or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes, as an adjunct to diet and exercise to improve glycemic control (as per approved label. HbA1c>7% and ≤10.5% at randomization. Men and women of 18-75 years of age. Women of childbearing potential must agree to use contraception or must not otherwise be at risk of becoming pregnant. A urine pregnancy test will be done at the time of screening and then every 4 weeks for the duration of 8 weeks. If positive, this will be confirmed with a serum pregnancy test which if positive, appropriate action will be taken as outlined in the detailed protocol. Blood pressure≥ 130/80 mm Hg and ≤160/100mmHg on stable treatment (no change in anti hypertensive treatment for 3 months prior to screening) or no treatment. No change in treatment for BP over 8 weeks of the study will be allowed. Patient understands the study procedures, alternative treatments are available, and the risks involved with the study, and voluntarily agree to participate by providing written informed consent. Exclusion Criteria: 1. Type 1 diabetes and/or history of ketoacidosis determined by medical history. 2. History of severe diabetic or autonomic neuropathy, gastroparesis or limb ulceration or amputation. 3. Therapy with DPP-4 inhibitor, or GLP -1 analog or receptor agonist in the past 6 months. 4. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures. 5. Patients on corticosteroids within 3 months or recurrent continuous corticosteroid treatment (>2 weeks). 6. Use of weight loss drugs within 3 months of screening or weight loss of ≥10 % in the last 6 months. 7. Surgery in the past 30 days prior to screening and/or any serious or chronic illness within 6 months or anticipated surgery during the trial period. 8. Serum creatinine >1.4mg/dL (women)/>1.5mg/dL (men). 9. Serum Triglyceride Level >500 mg/dL. 10. History of pancreatitis. 11. History of drug or alcohol abuse. 12. Poor mental function or any reason to expect patient difficulty in complying with study requirements. 13. Contraindications to Liraglutide: Personal or family history of medullary thyroid cancer or MEN-2 syndrome 14. Known or suspected allergy to Liraglutide. 15. Diagnosed Secondary hypertension.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liraglutide<br>All subjects will be advised a low sodium diet. This will be a placebo controlled, double blind and randomized trial of effects of Liraglutide on systolic BP control. Eligible patients will have ABPM measurements and laboratory blood collection at baseline (prior to initiation of Liraglutide or Placebo), at 4 and 8 weeks of therapy. Patients will return 24 hours following ABPM placement for device and data retrieval. Each subject will be asked to keep a log of activities throughout the day. | Drug: Liraglutide or Placebo<br>* All subjects will be advised a low sodium diet. Eligible patients will have ABPM measurements and laboratory blood collection at baseline (prior to initiation of Liraglutide or Placebo), at 4 and 8 weeks of therapy. Patients will return 24 hours following ABPM placement for device and data retrieval.<br>* Other names: Victoza;|
| Placebo Comparator: Placebo<br>All subjects will be advised a low sodium diet. This will be a placebo controlled, double blind and randomized trial of effects of Liraglutide on systolic BP control. Eligible patients will have ABPM measurements and laboratory blood collection at baseline (prior to initiation of Liraglutide or Placebo), at 4 and 8 weeks of therapy. Patients will return 24 hours following ABPM placement for device and data retrieval. Each subject will be asked to keep a log of activities throughout the day. | Drug: Liraglutide or Placebo<br>* All subjects will be advised a low sodium diet. Eligible patients will have ABPM measurements and laboratory blood collection at baseline (prior to initiation of Liraglutide or Placebo), at 4 and 8 weeks of therapy. Patients will return 24 hours following ABPM placement for device and data retrieval.<br>* Other names: Victoza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitors. | To determine whether Liraglutide lowers systolic BP through the day compared to placebo in patients with T2DM who are not on any anti-hypertensive medications or whose BP medications are unchanged over the study period of 8 weeks. | Baseline and 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pulse Pressure, Mean Arterial, Diastolic and Nocturnal Blood Pressures. | Change in mean arterial blood pressure and diastolic blood pressure from baseline to 8 weeks in the intent-to-treat (ITT) population. Change in nocturnal BP: the absence of the nocturnal (between 23:00-06:00 hrs) decline in BP of >/= 10% (defined as non-dippers) and whether restoration occurs following Liraglutide therapy. Change in pulse pressure: defined as the difference in systolic and diastolic BPs from baseline to week 8. | Baseline and 8 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, Hypertension, ambulatory blood pressure monitoring, Endothelial Dysfunction, Pulse pressure, Renin-angiotensin system, heart rate variability