Losartan vs. Hydrochlorothiazide in Reversing Remodeling of Small Arteries in Pre-Hypertensive Pre-Diabetic Subjects - Clinical Trials for Diabetic Hypertension

Losartan vs. Hydrochlorothiazide in Reversing Remodeling of Small Arteries in Pre-Hypertensive Pre-Diabetic Subjects
This study is currently recruiting participants.
Verified by Sir Mortimer B. Davis - Jewish General Hospital, March 2007
Sponsors and Collaborators: Sir Mortimer B. Davis - Jewish General Hospital
Merck Frosst Canada Ltd.

Information provided by: Sir Mortimer B. Davis - Jewish General Hospital
ClinicalTrials.gov Identifier: NCT00388388

Purpose
This randomized, double-blind, parallel group, two-centre pilot study will test the hypothesis that subjects who are otherwise healthy but fulfill the criteria for a diagnosis of pre-hypertension and pre-diabetes will have regression or reduced progression of hypertension-associated changes in their resistance arteries if their blood pressure is controlled for 6 months with losartan, whereas similar subjects whose blood pressure is equally well controlled using hydrochlorothiazide will have significantly less improvement of the changes in their resistance arteries.

Condition Intervention Phase
Pre-Hypertension
Pre-Diabetes
Drug: losartan, hydrochlorothiazide
Phase II

MedlinePlus related topics: Diabetes High Blood Pressure
Drug Information available for: Hydrochlorothiazide Losartan Losartan potassium
U.S. FDA Resources
Study Type:Interventional
Study Design:Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study
Official Title:Double-Blind, Randomized, Parallel Design Study Comparing Effectiveness of Losartan vs. Hydrochlorothiazide in Reversing or Preventing the Progression of the Remodeling of Resistance Arteries in Pre-Hypertensive Pre-Diabetic Subjects

Further study details as provided by Sir Mortimer B. Davis - Jewish General Hospital:

Primary Outcome Measures:
Effect of 6 months of losartan or hydrochlorothiazide on media/lumen ratio of gluteal subcutaneous resistance arteries in otherwise normal subjects who fulfill criteria for pre-hypertension and pre-diabetes

Secondary Outcome Measures:
Safety and tolerability of 6 month therapy with losartan or hydrochlorothiazide, and effect on media thickness, lumen diameter and vascular function of gluteal subcutaneous resistance arteries, and serum and tissue inflammatory markers in same subjects

Estimated Enrollment:30
Study Start Date:March 2007

Eligibility
Ages Eligible for Study:25 Years to 70 Years
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No
Criteria
Inclusion Criteria:

Prehypretensive prediabetic subjects (25-70 years old) defined as otherwise normal subjects with a mean SiSBP of 120-139 mmHg and fasting blood glucose of 6.1-6.9 mmol/L at screening and after two weeks of placebo therapy (Week -2)
Exclusion Criteria:

Hypertension or clinically significant renal disease
Cerebrovascular accident within the past year, or current transient ischemic attacks
Myocardial infarction within the past year; percutaneous coronary angioplasty or coronary artery bypass surgery within last 6 months
Clinically significant AV conduction disturbances and/or arrhythmias (e.g. second- or third-degree AV block; sick-sinus syndrome or clinically significant bradycardia- resting heart rate < 45 beats/minute), tachyarrhythmias; clinically significant arrhythmias, presence of accessory bypass tract (e.g. Wolff-Parkinson-White syndrome)
Angina pectoris
Current or prior history of heart failure or known left ventricular ejection fraction <40%
History of unexplained syncope or known syncopal disorder (e.g., Stokes-Adams Syndrome)
Known history of hemodynamically significant obstructive valvular disease or hypertrophic cardiomyopathy
Use of agents that may cause alteration of blood pressure is prohibited. This includes nitrates, or alpha or beta-blockers. Calcium channel blockers are allowed as second line therapy if hypertension develops during the study Major psychotropic agents and antidepressants are not permitted
Cimetidine is not permitted (famotidine and ranitidine and proton pump inhibitors are allowed).
NSAIDs are permitted if taken on a stable regimen. Aspirin in small doses (< 1 g/day) as cardioprotective agent and acetaminophen are permitted
Oral or inhaled steroids, ACTH, immunosuppressants or lithium are not allowed
Serum creatinine concentration >200 ìmol/L (adjusted for age and weight)
Urine dipstick or microscopic findings suggestive of significant renal or other disease.
Hematuria should be evaluated, the etiology established/documented, and treatment rendered as appropriate prior to entry
Off-treatment serum potassium concentration >5.5 mmol/L or <3.5 mmol/L
AST (SGOT) or ALT (SGPT) >2 x normal upper limit
Clinically significant laboratory values outside of the established normal range including but not limited to the following parameters: hemoglobin, platelet count or white blood cell count
Known hypersensitivity or contraindication to losartan or thiazide diuretics
History of clinically important malabsorption or gastrointestinal resection
Current urinary tract infection
Smoking 10 cigarettes or more.
Pregnancy or lactating females. Females of childbearing age who are not surgically sterilized and are using effective contraception may enter only if an exclusionary pregnancy test is done within 72 hours of the first double-blind dose of test agent. Pregnancy tests will then be done monthly throughout the study.
Vasculitis or vasculopathy: collagen-vascular diseases, chronic hepatitis B antigenemia, circulating immune complexes, complement disorders, amyloidosis, scleroderma, etc. Neoplasms, Acquired Immunodeficiency Syndrome (AIDS), or HIV positive
Bleeding or platelet disorder
Known absence of one kidney
Subjects abusing or who within past two years abused alcohol or other drug substances
Mentally or legally incapacitated subjects
Subjects who have participated in another investigational drug trial, including those using marketed drugs (i.e. patient has signed a consent form), within the 28 days prior to start of placebo therapy
Subjects who, in the opinion of the investigator, will not cooperate fully, keep appointments or are unreliable
Inability or unwillingness to sign the Patient Consent Form
Phase V of Korotkoff sounds cannot be detected
Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00388388

Contacts
Contact: Ernesto L. Schiffrin, MD, PhD 514-340-8222 ext 4835 ernesto.schiffrin@mcgill.ca
Contact: Ranjan Sudra 514-340-7538 rsudra@mtd.jgh.mcgill.ca

Locations
Canada, Quebec
Cardiovascular Prevention Centre, Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Ernesto L. Schiffrin, MD, PhD 514-340-8222 ext 4030 ernesto.schiffrin@mcgill.ca
Contact: Tracy Hodge, RN 514-340-8222 ext 4030 tract.hodge@jgh.mcgill.ca
Principal Investigator: Ernesto L. Schiffrin, MD, PhD

Sponsors and Collaborators
Sir Mortimer B. Davis - Jewish General Hospital
Merck Frosst Canada Ltd.
Investigators
Principal Investigator: Ernesto L. Schiffrin, MD, PhD Physician-Chief, SMBD - Jewish General Hospital & Professor of Medicine, McGill University

Sir Mortimer B. Davis - Jewish General Hospital and Lady Davis Institute for Medical Research

Publications:
Schiffrin EL, Park JB, Intengan HD, Touyz RM. Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation. 2000 Apr 11;101(14):1653-9.
Park JB, Intengan HD, Schiffrin EL. Reduction of resistance artery stiffness by treatment with the AT(1)-receptor antagonist losartan in essential hypertension. J Renin Angiotensin Aldosterone Syst. 2000 Mar;1(1):40-5. Erratum in: J Renin Angiotensin Aldosterone Syst 2000 Jun;1(2):124.
Schiffrin EL, Park JB, Pu Q. Effect of crossing over hypertensive patients from a beta-blocker to an angiotensin receptor antagonist on resistance artery structure and on endothelial function. J Hypertens. 2002 Jan;20(1):71-8.
Savoia C, Touyz RM, Endemann DH, Pu Q, Ko EA, De Ciuceis C, Schiffrin EL. Angiotensin receptor blocker added to previous antihypertensive agents on arteries of diabetic hypertensive patients. Hypertension. 2006 Aug;48(2):271-7. Epub 2006 Jun 19.

Study ID Numbers:CPC030
First Received:October 13, 2006
Last Updated:April 30, 2007
ClinicalTrials.gov Identifier:NCT00388388 [history]
Health Authority:Canada: Health Canada; Canada: Ethics Review Committee

Keywords provided by Sir Mortimer B. Davis - Jewish General Hospital:
Remodeling
Resistance arteries
angiotensin receptor blocker
thiazide diuretic

Study placed in the following topic categories:
Losartan
Metabolic Diseases
Glucose Intolerance
Diabetes Mellitus
Prediabetic State
Disease Progression
Vascular Diseases
Endocrine System Diseases
Angiotensin II
Hydrochlorothiazide
Hyperglycemia
Endocrinopathy
Glucose Metabolism Disorders
Metabolic disorder
Hypertension

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Diuretics
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions
Membrane Transport Modulators
Angiotensin II Type 1 Receptor Blockers
Natriuretic Agents
Therapeutic Uses
Cardiovascular Diseases
Anti-Arrhythmia Agents