To Evaluate the Effect of Liraglutide on Ambulatory Blood... | NCT02299388

NCT02299388

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Novo Nordisk A/S	INDUSTRY

Description Module

Detailed Description

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Liraglutide	Active Comparator	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
Placebo	Placebo Comparator	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Liraglutide or Placebo	Drug	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.

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Other Outcomes

Measure	Description	Time Frame
Change in Endothelial Function. (Using Endo PAT)	To understand the BP lowering effect of Liraglutide, the investigators will study the Endothelial function - using Endo PAT	Baseline and 8 Weeks
Change in Autonomic Function (Heart Rate Variability Using Endo PAT.)

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Tina Thethi, MD	AdventHealth	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Tulane University Health Science Center, Tidewater building and Tulane Hospital and Clinics		New Orleans	Louisiana	70112	United States

Arm/Group Information

ID	Title	Description
FG000	Liraglutide	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. Liraglutide or Placebo: 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.
FG001	Placebo	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. Liraglutide or Placebo: 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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Liraglutide	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. Liraglutide or Placebo: 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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Only 2 subjects in the placebo group completed 80% ambulatory blood pressure measurements at visits 2 (baseline) and visit 5 (8 weeks).

Posted

Mean

Full Range

mm/Hg

Baseline and 8 Weeks

ID	Title	Description
OG000	Liraglutide	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. Liraglutide or Placebo: 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Liraglutide	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. Liraglutide or Placebo: 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.

ID	Term
D003924	Diabetes Mellitus, Type 2
D006973	Hypertension

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones