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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02299388

Enrollment

Registered

2014-11-24

Start date

2014-10-31

Completion date

2016-12-31

Last updated

2021-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Non-Insulin-Dependent, Hypertensive Disease

Keywords

Type 2 Diabetes Mellitus, Hypertension, ambulatory blood pressure monitoring, Endothelial Dysfunction, Pulse pressure, Renin-angiotensin system, heart rate variability

Brief summary

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.

Interventions

DRUGLiraglutide 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change in Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitors.	Baseline and 8 Weeks	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.

Secondary

Measure	Time frame	Description
Change in Pulse Pressure, Mean Arterial, Diastolic and Nocturnal Blood Pressures.	Baseline and 8 Weeks	1. Change in mean arterial blood pressure and diastolic blood pressure from baseline to 8 weeks in the intent-to-treat (ITT) population. 2. 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. 3. Change in pulse pressure: defined as the difference in systolic and diastolic BPs from baseline to week 8.

Other

Measure	Time frame	Description
Change in Renin-Angiotensin System (Plasma Renin and Aldosterone Levels and Urine Angiotensinogen Levels)	Baseline and 8 Weeks	To understand the mechanisms of BP lowering effect of Liraglutide, the investigators will study the effects on Renin Angiotensin system by measuring Plasma renin and aldosterone levels and Urine Angiotensinogen levels (U-AGT-using an assay developed at Tulane Hypertension Center).
Change in Endothelial Function. (Using Endo PAT)	Baseline and 8 Weeks	To understand the BP lowering effect of Liraglutide, the investigators will study the Endothelial function - using Endo PAT
Change in Urinary Sodium Excretion	Baseline and 8 Weeks	To understand the BP lowering effect of Liraglutide, the investigators will assess urinary sodium excretion by collecting 24 hours Urine Sodium.
Change in Catecholamines (Collecting 24 Hrs Urine for Metanephrines and Catecholamines.)	Baseline and 8 Weeks	To understand the BP lowering effect of Liraglutide, the investigators will analyse the catecholamines by collecting 24 hrs urine for metanephrines and catecholamines.
Change in Autonomic Function (Heart Rate Variability Using Endo PAT.)	Baseline and 8 Weeks	To understand the BP lowering effect of Liraglutide, the investigators will study the the autonomic function by assessing the heart rate variability using Endo PAT.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	6
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.	5
Total	11

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Liraglutide	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	2 Participants	3 Participants
Age, Categorical Between 18 and 65 years	5 Participants	3 Participants	8 Participants
Age, Continuous	57.67 years	59.8 years	58.64 years
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants	5 Participants	11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	3 Participants	5 Participants	8 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	0 Participants	3 Participants
Region of Enrollment United States	6 Participants	5 Participants	11 Participants
Sex: Female, Male Female	3 Participants	5 Participants	8 Participants
Sex: Female, Male Male	3 Participants	0 Participants	3 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 5
other Total, other adverse events	0 / 6	0 / 5
serious Total, serious adverse events	0 / 6	0 / 5

Outcome results

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.