Clinical trial NCT03956823: Clinical Efficacy of Telmisartan in Reducing Cardiac Remodeling Among Obese Patients With Hypertension
Official title: A Cohort Study of Telmisartan on Metabolic Components and Left Ventricular Remodeling in Obese Patients With Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypertension
Keywords: hypertension
obesity
telmisartan
metabolic abnormalities
cardiac remodeling
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2019-05-21
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypertension is closely related to metabolic abnormalities such as obesity, dyslipidemia and diabetes. When hypertension is complicated with metabolic abnormalities, target organ damage is more serious, the risk of cardiovascular adverse events is greater, and the treatment is more complex. The pathophysiological mechanism of obesity-associated hypertension has its particularity. Blood pressure control and effective control of obesity are important therapeutic targets. At present, there are no guidelines for the treatment of obesity-associated hypertension. Although several drugs have certain effects on fat metabolism, they have little effect on blood pressure and have some side effects in long-term use. Among the existing antihypertensive drugs, angiotensin II type 1 receptor (AT-1) antagonists have shown their particularity in improving glycolipid metabolism, but strict clinical trials are needed to confirm their effectiveness in weight loss and metabolism improvement. Previous studies have shown that obese patients with hypertension have severe insulin resistance, poor glycolipid metabolism and are prone to cardiovascular damage. Telmisartan can block AT-1 receptor and partially activate PPAR-γ, increase the expression of PPAR-γ target gene in preadipocytes, improve the function of visceral adipose tissue, and effectively prevent obesity-related cardiovascular diseases. It is presumed that telmisartan can act as a PPAR-γ agonist in clinic by altering the metabolic components and insulin sensitivity, but there is no clinical evidence for this. On the basis of previous studies, this study aims to evaluate the clinical efficacy of telmisartan or amlodipine in controlling blood pressure, reducing fat accumulation, improving insulin sensitivity, and reducing cardiac remodeling in obese patients with hypertension by prospective cohort study.

Detailed description: At present, there are no guidelines for the treatment of obese patients with hypertension. Blood pressure control and effective control of obesity are important therapeutic targets for obesity-associated hypertension. Whether telmisartan can be used as PPAR-γ agonist, unlike other AT-1 receptor antagonists and calcium channel blockers amlodipine, can improve the visceral adipose tissue function and cardiac remodeling in obese patients with hypertension by altering their metabolic components and insulin sensitivity while controlling blood pressure. There is no evidence that telmisartan can reduce cardiac remodeling in obese patients with hypertension.

1.Research contents:

1. To evaluate the clinical efficacy of telmisartan or amlodipine in controlling blood pressure, reducing fat accumulation, improving glycolipid metabolism and insulin sensitivity, and reducing cardiac remodeling in obese patients with hypertension;
2. To evaluate whether telmisartan can alter metabolic components and insulin sensitivity, improve visceral adipose tissue function and reduce cardiac remodeling in obese patients with hypertension by blocking AT-1 receptor and partially activating PPAR-gamma, which is different from other AT-1 receptor antagonists and calcium channel blockers amlodipine.

2.Research population 2.1 Entry criteria

Only those who possess the following four conditions can enter the study:

1. Essential hypertension patients (including confirmed hypertension without regular treatment, average blood pressure (≥160 or/and 100 mmHg) in two follow-up visits; or hypertension under combined antihypertensive treatment; or unsatisfactory blood pressure control with single drug treatment, blood pressure above 140 or/and 90 mmHg)；
2. Age ranges from 18 to 79；
3. Body mass index, BMI (≥30 kg/m2), or waist circumference, male (≥102 cm), female (≥ 88 cm)；
4. Ability to provide informed consent。

2.2 exclusion criteria

One of the following is not included:

(1) secondary hypertension; (2) acute cardiovascular and cerebrovascular events within 3 months; (3) severe cardiomyopathy, rheumatic heart disease, congenital heart disease;(4) unstable angina pectoris; (5) severe liver or kidney disease (ALT increased by 2 times; Creatinine \> 2. 5 mg/dL); (6) malignant tumors; (7) gout; (8) women who are taking birth control pills or are at risk of pregnancy; (9) have a history of allergy to research drugs; (10) patients with specific contraindications to the study drugs; (11) participants in other clinical trials; (12) patients with difficulty in long-term follow-up or poor compliance; (13) the competent doctor considers it inappropriate to participate in clinical research.

3.The input information of the subjects

1. Sample source: Since December 2018, patients with essential hypertension were diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University and treated with telmisartan or amlodipine alone under the guidance of doctors；
2. Recruitment procedures: selecting the subjects according to inclusion and exclusion criteria, and signing informed consent.

4.Criteria for termination or withdrawal of research subjects

1. Those who need revascularization because of myocardial infarction and unstable angina pectoris;
2. Heart failure;
3. Stroke.

5. Study Groups

1. Telmisartan group: Telmisartan 80 mg once a day
2. amlodipine group: amlodipine 5 mg once a day

6.Research evaluation index

1. Baseline indicators: age, sex, occupation, height, weight, BMI, waist-hip circumference, systolic blood pressure, diastolic blood pressure, heart rate;
2. Metabolic indicators: blood lipid, liver function, kidney function, oral glucose tolerance test, simultaneous insulin release test, plasma Glucagon, plasma aldosterone, plasma angiotensin II, abdominal fat distribution
3. Fat function: serum leptin, serum adiponectin, serum TNFalpha, serum IL-6, serum hs-CRP, serum PPAR-γ;
4. Cardiac remodeling: echocardiographic parameters .

7.Research steps

1. Clinical trials are ethically reviewed by ethics committees, and clinical trials are registered;
2. Collect cases according to inclusion and exclusion criteria, collect medical history data of subjects, and complete follow-up. At the same time, clinical and biochemical experiments were carried out;
3. Comprehensive analysis of experimental data, repetition and supplementation of necessary molecular biological experiments, comprehensive summary of the results, writing and publishing SCI papers and Chinese core journal papers.

Eligibility criteria: Inclusion Criteria:

* Essential hypertension patients (including those with unconventional diagnosed hypertension, whose average blood pressure was more than 160 or/and 100 mmHg in two outpatient follow-up visits; or those who were undergoing combined antihypertensive therapy; or those whose blood pressure control was unsatisfactory and whose blood pressure was more than 140 or/and 90 mmHg in single drug treatment);
* The age ranged from 18 to 79 years;
* Body mass index, BMI (≥ 30 kg/m2), or waist circumference, male (≥102 cm), female (≥88 cm);
* Ability to provide informed consent.

Exclusion Criteria:

* Secondary hypertension;
* Acute cardiovascular and cerebrovascular events occurred within 3 months;
* Complicated with severe cardiomyopathy, rheumatic heart disease, congenital heart disease;
* unstable angina pectoris;
* Severe liver or kidney diseases (ALT increased twice; creatinine \> 2.5 mg/d1);
* Tumor；
* Gout;
* Women who are taking contraceptives or are at risk of pregnancy; -Has a history of allergy to research drugs;
* Those who have clear contraindications to the research drugs;
* Those who are participating in other clinical trials;
* Those who are not easy to follow up for a long time or have poor compliance;
* Doctors in charge do not consider it advisable to participate in clinical research.

Primary outcomes:
measure: Revascularization for myocardial infarction and unstable angina pectoris
timeFrame: From date of randomization until the date of first documented progression，assessed up to 24 months
measure: Heart failure
timeFrame: From date of randomization until the date of first documented progression，assessed up to 24 months
measure: stroke
timeFrame: From date of randomization until the date of first documented progression，assessed up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Gang Tian, doctor
role: PRINCIPAL_INVESTIGATOR
References: