CR Aim #2 - AT1 Receptor Blockade & ACE Inhibition Effect on Humoral Function

NCT01678794 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 09-0032841R01HL084155-01A2
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

To advance our understanding of the mechanisms of human cardiorenal syndrome with emphasis upon the interaction of diuretic therapy and the renal-angiotensin-aldosterone -system and cGMP pathway. The belief is that the chronic AT1 receptor blockade in subjects with compensated CHF and renal dysfunction will improve renal function with increased sodium excretion, glomerular filtration rate and effective renal plasma flow and renal function reserve as compared to the response of placebo-treated subjects.

Conditions

Cardiorenal Syndrome (CRS)

Keywords

Chronic heart failure (CHF); cardiac and renal dysfunction

Outcome Measures

Primary Outcomes (2)

• Change in Glomerular Filtration Rate

  Glomerular Filtration Rate estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood. Measured as ml/min/1.73 m2

  baseline to 3 months

• Change in Urinary Sodium Excretion

  Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. The body continually monitors blood volume and sodium concentration. When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal. Measured as mEq/min

  baseline to 3 months

Study Arms (2)

Candesartan

EXPERIMENTAL

Drug: Candesartan

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Candesartan DRUG

4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated

Also known as: Atacand

Candesartan

Placebo DRUG

4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated

Placebo

Eligibility Criteria

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

You may qualify if:

• Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months.
• Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months, on stable doses of ACE inhibitor, beta blocker, digoxin and furosemide over the last 4 weeks and no episode of decompensated CHF over the past 6 months.
• Calculated creatinine clearance of equal or less than 80 ml/min and greater than 20 ml/min, using the MDRD formula assessed within the past 48 months and a confirmatory calculated creatinine clearance equal or less than 80 ml/min and greater than 20 ml/min at the time of enrollment.

You may not qualify if:

• Prior diagnosis of intrinsic renal diseases including renal artery stenosis of \> 50%
• Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
• Hospitalization for decompensated CHF during the past 6 months
• Subjects that are taking AT1 receptor blockers
• Myocardial infarction within 6 months of screening
• Unstable angina within 6 months of screening, or any evidence of myocardial ischemia
• Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
• Severe congenital heart diseases
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
• Second or third degree heart block without a permanent cardiac pacemaker
• Stroke within 3 months of screening, or other evidence of significantly compromised CNS perfusion
• ALT \>1.5 times the upper limit of normal
• Serum sodium of \< 125 mEq/dL or \> 160 mEq/dL
• Serum potassium of \< 3.5 mEq/dL or \> 5.7 mEq/dL
• Serum digoxin level of \> 2.0 ng/ml

Sponsors & Collaborators

• Mayo Clinic: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Cardio-Renal Syndrome; Renal Insufficiency

Interventions

candesartan; candesartan cilexetil

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Failure; Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Horng H. Chen, M.D.
• Organization: Mayo Clinic

chen.horng@mayo.edu

507-284-8896

Study Officials

• Horng H. Chen, M.D.

  Mayo Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: August 31, 2012
• First Posted: September 5, 2012
• Study Start: February 1, 2012
• Primary Completion: June 29, 2016
• Study Completion: June 29, 2016
• Last Updated: November 18, 2021
• Results First Posted: November 18, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)