Pre-diabetes Clinical Trial
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
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.
Status | Terminated |
Enrollment | 1 |
Est. completion date | December 2009 |
Est. primary completion date | December 2009 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 25 Years to 70 Years |
Eligibility |
Inclusion Criteria: - 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) 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 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 - 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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Canada | Cardiovascular Prevention Centre, Jewish General Hospital | Montreal | Quebec |
Lead Sponsor | Collaborator |
---|---|
Sir Mortimer B. Davis - Jewish General Hospital | Merck Frosst Canada Ltd. |
Canada,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | No | |
Secondary | 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 | Yes |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04082585 -
Total Health Improvement Program Research Project
|
||
Enrolling by invitation |
NCT05367024 -
Broccoli Effect on Glycated Haemoglobin (HbA1c)
|
N/A | |
Withdrawn |
NCT02400450 -
Designer Functional Foods on Parameters of Metabolic and Vascular in Prediabetes
|
N/A | |
Completed |
NCT02933424 -
Project Plant Protein: the P3 Study in Humans
|
N/A | |
Completed |
NCT02656212 -
Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin (Part 2)
|
Phase 1 | |
Completed |
NCT02330276 -
Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin
|
Phase 1 | |
Completed |
NCT01488279 -
Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy
|
N/A | |
Completed |
NCT00831129 -
A Study for Pre-diabetic Patients With Cholesterol Lowering Drugs
|
Phase 2/Phase 3 | |
Completed |
NCT00536250 -
Study to Investigate the Pathophysiology of Type 2 Diabetes in Youth
|
N/A | |
Recruiting |
NCT05563090 -
Investigating the Syndrome Differentiation of Diabetic and Pre-diabetic Using Digitalized TCM Diagnostic Tools
|
||
Active, not recruiting |
NCT04991142 -
Models of Nutrition From Continuous Glucose Monitors
|
||
Completed |
NCT02759055 -
Pre-Diabetes Cardiovascular (CV) Care (Pre-Diabetes Wizard)
|
N/A | |
Completed |
NCT00775684 -
Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass
|
N/A | |
Completed |
NCT03695913 -
Continuous Glucose Monitoring (CGM) With a Low Carbohydrate Diet to Reduce Weight in Patients With Pre-Diabetes
|
N/A | |
Completed |
NCT04051008 -
CTSI Pilot: Improving Adherence to Diabetic Diet
|
N/A | |
Recruiting |
NCT04897945 -
A Shared Decision Making Intervention for Diabetes Prevention in Women With a History of Gestational Diabetes Mellitus
|
N/A | |
Not yet recruiting |
NCT04442451 -
Mechanisms of Fatigability With Diabetes
|
N/A | |
Not yet recruiting |
NCT05925933 -
High Protein Diet on Transcriptomic, Metabolomics, Hepatic and Pancreatic Fat Anatomy and Physiology in Asian Indians With Pre-diabetes
|
N/A | |
Active, not recruiting |
NCT05654051 -
The SLIM LIVER Study
|
Phase 2 | |
Completed |
NCT02919397 -
Motivational Instant Messaging and E-diabetes Prevention Programme for High Risk of Type 2 Diabetes
|
N/A |