Losartan Versus Hydrochlorothiazide in Reversing Remodeling of Small Arteries in Pre-Hypertensive Pre-Diabetic Subjects

NCT00388388 | Terminated Phase 2 DMC

• 1 other identifier: CPC030
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pre-hypertension; Pre-diabetes

Keywords

Remodeling; Resistance arteries; angiotensin receptor blocker; thiazide diuretic

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (1)

• 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

  6 months

Study Arms (2)

1

EXPERIMENTAL

Losartan treatment

Drug: losartan, hydrochlorothiazide

2

ACTIVE COMPARATOR

Hydrochlorothiazide, 12.5-25 mg per day once a day for 6 months

Drug: losartan, hydrochlorothiazide

Interventions

losartan, hydrochlorothiazide DRUG

Losartan, 50-100 mg per day, once a day, for 6 months. Hydrochlorothiazide, 12.5-25 mg per day, once a day, for 6 months.

Also known as: Cozaar, Apo-hydro

1; 2

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prehypertensive 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 or impaired glucose tolerance on oral glucose tolerance test (OGTT) at screening and after two weeks of placebo therapy (Week -2)

You may not qualify if:

• 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 μmol/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

Sponsors & Collaborators

• Sir Mortimer B. Davis - Jewish General Hospital: lead
• Merck Frosst Canada Ltd.: collaborator

Study Sites (1)

Cardiovascular Prevention Centre, Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (4)

• 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. doi: 10.1161/01.cir.101.14.1653.

  PMID: 10758046 BACKGROUND

• 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. doi: 10.3317/jraas.2000.009.

  PMID: 11967798 BACKGROUND

• 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. doi: 10.1097/00004872-200201000-00011.

  PMID: 11791028 BACKGROUND

• 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. doi: 10.1161/01.HYP.0000230234.84356.36. Epub 2006 Jun 19.

  PMID: 16785331 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Prehypertension; Glucose Intolerance

Interventions

hydrochlorothiazide, losartan drug combination; Losartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Ernesto L. Schiffrin, MD, PhD

  Physician-Chief, SMBD - Jewish General Hospital & Professor of Medicine, McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician-in-Chief

Study Record Dates

• First Submitted: October 13, 2006
• First Posted: October 16, 2006
• Study Start: March 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 19, 2015

Record last verified: 2015-05

Locations

CA (1)