Aliskiren vs Hydrochlorothiazide in Hypertensive Type II Diabetic Patients on Resistance Arteries

NCT01480791 | Withdrawn Phase 2

• 1 other identifier: CSPP100ACA03T
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be performed only at the Jewish General Hospital. It will investigate the effect of treatment with aliskiren, an inhibitor of renin, a substance produced by the kidney that constricts arteries and raises blood pressure, on the blood vessels, specifically the arteries, of subjects who have diabetes and elevated blood pressure (hypertension). To investigate blood vessels, different techniques will be used. For large arteries, these will be studied by non invasive methods using detection of the pulse wave or using ultrasound over the skin of the neck, the wrist and the groin. To study small vessels, the investigators will perform a biopsy on the buttock, under local anesthesia, and obtain a small sample of tissue from under the skin, from which the vessels will be dissected. The investigators have performed many hundreds of these small biopsies over the past 20 years for similar studies without any complications. The biopsies are very well tolerated. From this research the investigators will thus be able to learn what the structure and function of these vessels is in these patients, in comparison to a normal healthy group. The hypertensive diabetic subjects will then be assigned by chance (randomized trial) to treatment with the renin inhibitor aliskiren or a comparator, the diuretic hydrochlorothiazide. Aliskiren is a relatively new drug used to treat hypertension that is very well tolerated and is now being evaluated in numerous trials in hypertensive diabetic individuals. The diuretic is a well-know agent used to treat high blood pressure now for many years, and which is very well tolerated. Physicians, nurses and scientists involved in the study will be unaware of who is receiving which drug, as will be the patients (this is the meaning of double-blind trial). However, if there is any problem, the secret code will be broken and the individual withdrawn from the study. Subjects will be treated for a year, and the study procedures (non invasive and the biopsy) repeated at 6 months and after one year of treatment. During the study, blood samples will be drawn and urine collected at certain intervals to ensure safety of the treatment. Once tissues are obtained they will be studied in the laboratory. The study of the vessels will allow treatment us to determine how the treatment with the renin inhibitor aliskiren affects the structure and function as well as cellular and molecular aspects of arteries of hypertensive diabetic persons. The investigators expect these studies to provide us knowledge on mechanisms and perhaps new targets for future therapies of cardiovascular disease and hypertension.

Conditions

Hypertension; Diabetes

Keywords

resistance arteries; endothelial dysfunction; aortic stiffness

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is baseline-adjusted change in media/lumen ratio in patients who were randomized to aliskiren (group 1) comparatively to those randomized to hydrochlorothiazide (group 2)

  The primary endpoint is baseline-adjusted change in media/lumen ratio in patients who were randomized to aliskiren (group 1) comparatively to those randomized to hydrochlorothiazide (group 2)

  6 months-1 year

Secondary Outcomes (3)

• Secondary outcome: Pulse wave velocity (PWV) of aorta in hypertensive diabetic patients randomized to aliskiren versus those who were randomized to HCTZ.

  6 months-1 year

• Augmentation index (AI) of patients randomized to either aliskiren or hydrochlorothiazide

  6 months-1 year

• Flow-mediated dilation in hypertensive diabetic patients randomized to aliskiren vs. hydrochlorothiazide

  6 months-1 year

Study Arms (3)

Hydrochlorothiazide

ACTIVE COMPARATOR

Treatment of patients with hydrochlorothiazide and effect on small arteries

Drug: Hydrochlorothiazide

Aliskiren

EXPERIMENTAL

Treatment of patients with aliskiren and effect on small arteries

Drug: Aliskiren vs. hydrochlorothiazide; Drug: Hydrochlorothiazide

Normotensive non diabetic subjects

NO INTERVENTION

A comparator non intervention normotensive non diabetic group of healthy subjects will be used for baseline comparison of primary and secondary endpoints

Interventions

Aliskiren vs. hydrochlorothiazide DRUG

Aliskiren will be used at increasing doses from 150 to 300 mg per day for 6-12 months.

Also known as: Aliskiren is Tekturna or Rasilez

Aliskiren

Hydrochlorothiazide DRUG

Hydrochlorothiazide will be used at increasing doses from 12.5 to 25 mg per day for 6-12 months.

Also known as: Hydrochlorothiazide is a generic drug.

Aliskiren; Hydrochlorothiazide

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hypertensive Group
• Diabetes mellitus (diagnosed for at least 6 months) will be defined by usual criteria based on basal glycemia or glucose tolerance test . Diabetes must be well controlled, with glycosylated hemoglobin below 0.08 (8%).
• Hypertension is defined as a mean SiSBP \> 130 mmHg or SiDBP of 85-115mmHg at the screening visit, and after two weeks of placebo therapy. (Hypertension will be considered essential if there is no evidence of an underlying treatable cause after suitable clinical and laboratory assessment. Hypertensive patients may be taking any antihypertensive agent except a renin inhibitor. They may be taking an ACE inhibitor or an ARB, which will not be discontinued. If they have been on HCTZ, they are eligible to participate.
• Subjects are 30-70 years old
• Informed Consent obtained by patient
• Diabetic defined as: hemoglobin A1C \< 0.06 ( 6%) and / or fasting glycemia \< 5.6mmol/L.
• Hypertensive defined as : SiSBP ≤120 mmHg and/or SiDBP ≤80mmHg
• Subjects are 30-70 years old
• Informed Consent obtained by patient

You may not qualify if:

• Uncontrolled diabetes ( defined as: preprandial glycemia usually above 10 mmol/L and glycosylated hemoglobin above 0.08).
• Renovascular hypertension
• History of malignant hypertension
• Sitting systolic blood pressure \> 210 mmHg
• Cerebrovascular accident within the past year, or current transient ischemic attacks
• History of myocardial infarction, percutaneous coronary angioplasty or coronary artery bypass surgery
• 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 an 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 a known syncopal disorder (e.g., Stokes-Adams Syndrome)
• Presence or known history of hemodynamically significant obstructive valvular disease or hypertrophic cardiomyopathy
• Hypertensive patients already taking a renin inhibitor.
• Concomitant treatment

Sponsors & Collaborators

• Sir Mortimer B. Davis - Jewish General Hospital: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Cardiovascular Prevention Centre, Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (3)

• 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

• 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

• Savoia C, Touyz RM, Amiri F, Schiffrin EL. Selective mineralocorticoid receptor blocker eplerenone reduces resistance artery stiffness in hypertensive patients. Hypertension. 2008 Feb;51(2):432-9. doi: 10.1161/HYPERTENSIONAHA.107.103267. Epub 2008 Jan 14.

  PMID: 18195160 BACKGROUND

Related Links

• Web page of Dr. Ernesto L. Schiffrin at Lady Davis Institute for Medical Research

MeSH Terms

Conditions

Hypertension; Diabetes Mellitus

Interventions

aliskiren; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ernesto L Schiffrin, MD, PhD

  SMBD-Jewish General Hospital

  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, Director of the Cardiovascular Prevention Center, Professor of Medicine, McGill University

Study Record Dates

• First Submitted: November 5, 2011
• First Posted: November 29, 2011
• Study Start: January 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: May 19, 2015

Record last verified: 2015-05

Locations

CA (1)