A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients - Full Text View

Purpose

The epidemic of obesity is associated with a considerable rise in the incidence of the metabolic syndrome, type 2 diabetes mellitus, and hypertension. Insulin resistance plays an important role in the pathogenesis of obesity related hypertension. These patients are at high risk to suffer from cardiovascular events. However, current guidelines for treatment of hypertension do not provide specific recommendation for the pharmacotherapy of obese hypertensive patients due to lack of prospective randomized intervention studies in non-diabetic obese hypertensive patients.

Aside from their antihypertensive effects, angiotensin II receptor blockers (ARB) were shown to improve insulin sensitivity. Furthermore, metformin is commonly used to treat the obese type 2 diabetes mellitus. Metformin can also lower body weight and increase insulin sensitivity. In a prospective, double-blind, double-dummy, randomized, parallel-group study, we will evaluate the effects of ARB (telmisartan and candesartan) or amlodipine combination with metformin on weight gain, visceral fat, and metabolic parameters in obese hypertensive patients without diabetes mellitus compared with obese hypertensives on ARB or amlodipine treatment alone. This study will help to develop future comprehensive treatment strategies and guidelines for obesity related hypertension.

Condition	Intervention	Phase
Hypertension Obesity	Drug: Telmisartan plus Metformin Drug: Telmisartan Drug: Candesartan Drug: Candesartan plus Metformin Drug: Amlodipine Drug: Amlodipine plus Metformin	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Which is the Best Treatment for Non-diabetic Hypertension With Obesity: Telmisartan, Amlodipine or Candesartan, Alone or Plus MEtformin? (HOT-ACME 1)

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines High Blood Pressure Obesity

Drug Information available for: Metformin Metformin hydrochloride Amlodipine Amlodipine besylate Candesartan Telmisartan Candesartan cilexetil

U.S. FDA Resources

Further study details as provided by Third Military Medical University:

Primary Outcome Measures:

Blood Pressure [ Time Frame: Baseline, 24 weeks(End of trial) ] [ Designated as safety issue: No ]
Metabolic profiles, including lipid profile and blood glucose [ Time Frame: Baseline, 24 weeks(End of trial) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Abdominal fat assessed by CT [ Time Frame: Baseline, 24 weeks(End of trial) ] [ Designated as safety issue: Yes ]
Obesity parameters, including waist circumference (WC) and body mass index (BMI) [ Time Frame: Baseline, 24 weeks(End of trial) ] [ Designated as safety issue: Yes ]
Insulin resistance assessed by fasting serum insulin and HOMA-IR [ Time Frame: Baseline, 24 weeks(End of trial) ] [ Designated as safety issue: Yes ]
Incidents of side effects between groups [ Time Frame: Baseline, 24 weeks(End of trial) ] [ Designated as safety issue: Yes ]

Enrollment:	360
Study Start Date:	February 2008
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group T Telmisartan	Drug: Telmisartan Telmisartan 80mg 1/d Other Name: Telmisartan Alone
Experimental: Group T+M Telmisartan plus Metformin	Drug: Telmisartan plus Metformin Telmisartan 80mg 1/d, Metformin 250mg 2/d Other Name: Telmisartan Plus Metformin
Experimental: Group C Candesartan	Drug: Candesartan Candesartan 8mg daily Other Name: Candesartan Alone
Experimental: Group C+M Candesartan pus Metformin	Drug: Candesartan plus Metformin Candesartan 8mg 1/d Metformin 250mg 2/d Other Name: Candesartan Plus Metformin
Active Comparator: Group A Amlodipine	Drug: Amlodipine Amlodipine 5mg 1/d Other Name: Amlodipine alone
Experimental: Group A+M Amlodipine plus Metformin	Drug: Amlodipine plus Metformin Amlodipine 5mg 1/d, Metformin 250mg 2/d Other Name: Amlodipine plus Metformin

Eligibility

Ages Eligible for Study:	30 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Grade 1 or 2 hypertension: 140mmHg≤SBP<180mmHg, and/or 90mmHg≤DBP<110mmHg
Waist circumference higher than 90cm in men, 80cm in women

Exclusion Criteria:

Diabetes
Grade 3 hypertension: SBP≥180mmHg, or DBP≥110mmHg
known allergy or hypersensitivity to trial drugs
Myocardial infarction or cerebrovascular accident in the year preceding the trial
Clinical Congestive Heart Failure
History of hepatitis or cirrhosis
History of kidney disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538486

Locations

China
The third hospital affiliated to the Third Military Medical University
Chongqing, China, 400042

Sponsors and Collaborators

Third Military Medical University

Investigators

Principal Investigator:	Zhiming Zhu, MD, PhD	The third hospital affiliated to the Third Military Medical University. China
Study Director:	Zhiming Zhu, MD, PhD	The third hospital affiliated to the Third Military Medical University. China

More Information

Publications:

He H, Zhao Z, Chen J, Ni Y, Zhong J, Yan Z, Li Y, Liu D, Pletcher MJ, Zhu Z. Metformin-based treatment for obesity-related hypertension: a randomized, double-blind, placebo-controlled trial. J Hypertens. 2012 Jul;30(7):1430-9. doi: 10.1097/HJH.0b013e328353e249.

Responsible Party:	Zhiming Zhu, Director of Dept. of Hypertension & Endocrinology, Third Military Medical University
ClinicalTrials.gov Identifier:	NCT00538486 History of Changes
Other Study ID Numbers:	HOT-ACME 1
Study First Received:	October 1, 2007
Last Updated:	May 12, 2013
Health Authority:	China: Ministry of Health

Keywords provided by Third Military Medical University:

Hypertension
Abdominal obesity
Treatment

Additional relevant MeSH terms:

Hypertension
Obesity
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Metformin
Amlodipine
Candesartan
Candesartan cilexetil
Telmisartan
Benzoates

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013

A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients (HOT-ACME)