Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease

NCT02791906 | Terminated Phase 2 Results

• 1 other identifier: 823665
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure (HF) is an epidemic and is a major burden on the US healthcare system. The most common cardiovascular endpoint is HF. Thus, novel interventions to prevent HF in chronic kidney disease (CKD) are highly desirable. This study will assess: the variability in the response to isosorbide mononitrate (ISMN) therapy; the degree of change in central hemodynamics and cardiac endpoints through analysis of changes in left ventricle (LV) mass, diffuse myocardial fibrosis, and myocardial systolic and diastolic function.

Conditions

Renal Insufficiency, Chronic

Keywords

Chronic Kidney Diseases; Chronic Kidney Insufficiency; Chronic Renal Diseases; Chronic Renal Insufficiency; Kidney Insufficiency, Chronic; Cardiac Failure; Congestive Heart Failure; Heart Decompensation; Heart Failure, Congestive; Myocardial Failure

Outcome Measures

Primary Outcomes (1)

• Change in LV Mass

  Variability seen in change in LV mass with ISMN administration measured with steady-state free precession cardiac MRI, outcomes reflect the change, in grams

  Measured at Baseline Visit and 24 Week Visit

Secondary Outcomes (4)

• Changes in Diffuse Myocardial Fibrosis

  Measured at Baseline Visit and 24 Week Visit

• Changes in Myocardial Systolic and Diastolic Function

  Measured at Baseline Visit and 24 visits

• Pulse Wave Reflection Magnitude

  Measured between Baseline Visit-Week 24

• Aerobic Capacity

  Change from Baseline at Week 24 reported

Study Arms (2)

ISMN Only

EXPERIMENTAL

Patients receive only ISMN

Drug: ISMN

ISMN AND Vitamin C

EXPERIMENTAL

Patients receive both ISMN and Vitamin C

Drug: ISMN; Dietary Supplement: Vitamin C

Interventions

ISMN DRUG

ISMN AND Vitamin C; ISMN Only

Vitamin C DIETARY_SUPPLEMENT

ISMN AND Vitamin C

Eligibility Criteria

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

You may qualify if:

• Chronic kidney disease stage 3
• Elevated left ventricular mass index or LV posterior wall thickness \>1.4 cm documented in a clinically indicated echocardiographic or MRI examination within the previous 24 months or electrocardiographic LV hypertrophy
• Stable medical therapy as defined by no addition, removal or change in dosage \>100% of Angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers, or calcium channel blockers for \> 30 days
• Current therapy with an ACE inhibitor, hydralazine or a statin, all of which have been shown to reduce nitrate tolerance

You may not qualify if:

• A clinically- indicated stress test demonstrating significant myocardial ischemia within 1 year of enrollment, not followed by coronary revascularization
• Rhythm other than sinus (i.e., atrial fibrillation)
• Non-cardiac condition limiting life expectancy to \<1 year
• Current or anticipated future need for long acting organic nitrate therapy
• Severe aortic or mitral valve disease
• Hypertrophic cardiomyopathy
• Known infiltrative or inflammatory myocardial disease (amyloid, sarcoid)
• Pericardial disease
• Primary pulmonary arteriopathy
• History of myocardial infarction, unstable angina, percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days, or requirement for either PTCA or CABG at the time of consent
• Resting heart rate (HR) \>100 bpm
• A reduced LV ejection fraction (EF\<50%)
• Known severe liver disease (AST \>3x normal, alkaline phosphatase or bilirubin \>2x normal)
• Allergy to ISMN
• Current therapy with phosphodiesterase inhibitors, such as sildenafil, vardanafil or tadalafil

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Heart Failure

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Associate Professor
• Organization: University of Pennsylvania

julio.chirinos@uphs.upenn.edu

2152007779

Study Officials

• Julio Chirinos, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 7, 2016
• Study Start: May 1, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: August 13, 2020
• Results First Posted: August 13, 2020

Record last verified: 2020-07

Locations

US (1)