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Trial record 8 of 533 for:    Recruiting, Not yet recruiting, Available Studies | "Renal Insufficiency, Chronic"

Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease

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ClinicalTrials.gov Identifier: NCT02791906
Recruitment Status : Recruiting
First Posted : June 7, 2016
Last Update Posted : September 7, 2018
Sponsor:
Information provided by (Responsible Party):
Julio A. Chirinos, University of Pennsylvania

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 CKD are highly desirable. This study will assess: the variability in the response to ISMN therapy; the degree of change in central hemodynamics and cardiac endpoints through analysis of changes in LV mass, diffuse myocardial fibrosis, and myocardial systolic and diastolic function.

Condition or disease Intervention/treatment Phase
Renal Insufficiency, Chronic Drug: ISMN Dietary Supplement: Vitamin C Phase 2

Detailed Description:
This is a open label, parallel arm, randomized study of ISMN with or without vitamin C to improve exercise capacity and LV remodeling in CKD. Twenty subjects with CKD will be enrolled in this study and three different daily doses of SR-ISMN will be administered over time accompanied by a random administration of vitamin C in half of the subjects (500 mg three times daily). Before administration of SR-ISMN, baseline assessments will be performed. These include arterial tonometry, Doppler echocardiography, reflection magnitude measurements, a bicycle exercise test, activity monitoring, cardiac MRI, 24-hour blood pressure monitoring, and blood drawing. After these assessments, a dose of 30 mg of SR-ISMN will be administered daily (either with or without vitamin C) for the first week, 60 mg SR-ISMN for the second week, and 120 mg for the third week. After each week, blood pressure and central hemodynamics will be assessed. The third week visit also includes the bicycle exercise study and initiating the long term dose (60 or 120 mg) of SR-ISMN. In the long-term phase, blood pressure and hemodynamics are assessed at 12-weeks post initiation of the study medication(s). After 24 weeks we will perform the final assessment, which includes the same tests performed during the baseline assessment. Enrollment will take place at the Hospital of the University of Pennsylvania and the Penn Presbyterian Medical Center.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease
Study Start Date : May 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ISMN Only
Patients receive only ISMN
Drug: ISMN
Experimental: ISMN AND Vitamin C
Patients receive both ISMN and Vitamin C
Drug: ISMN
Dietary Supplement: Vitamin C



Primary Outcome Measures :
  1. Change in LV mass [ Time Frame: Measured at Baseline Visit and 24 Week Visit ]
    Variability seen in change in LV mass with ISMN administration measured with steady-state free precession cardiac MRI


Secondary Outcome Measures :
  1. Changes in Diffuse Myocardial Fibrosis [ Time Frame: Measured at Baseline Visit and 24 Week Visit ]
    Variability in the changes in diffuse myocardial fibrosis with ISMN administration using T1-mapping MRI techniques

  2. Changes in myocardial systolic and diastolic function [ Time Frame: Measured at Baseline Visit and weeks 3, 12, and 24 visits ]
    Variability in changes in myocardial systolic and diastolic function with ISMN administration, assessed via systolic strain (measured with displacement encoded MRI, DENSE) and early diastolic mitral annular velocity (measured with tissue Doppler echocardiography),

  3. Pulse Wave Reflection Magnitude [ Time Frame: Measured at Baseline Visit and weeks 1, 2, 3, 12, and 24 visits ]
    Measured by arterial tonometry and echocardiography

  4. Aerobic Capacity [ Time Frame: Measured at Baseline Visit and weeks 3, and 24 visits ]
    Variability in changes in aerobic capacity (peak oxygen consumption during maximal supine bicycle exercise test)

  5. Vasodilatory Reserve to Exercise [ Time Frame: Measured at Baseline Visit and weeks 3, and 24 visits ]
    reduction in systemic vascular resistance with exercise, measured with Doppler echocardiography

  6. Physical Activity [ Time Frame: Measured at Baseline Visit; week 1; week 2; week 3; two weeks prior to week 12 visit; two weeks prior to week 24 visit ]
    physical activity assessed via actigraphy



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 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

Exclusion Criteria:

  • 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
  • Therapy with rosiglitazone
  • Current pregnancy or a positive urine pregnancy test; women who become pregnant during the study will be discontinued from the trial
  • Therapy with warfarin
  • History of kidney stones
  • History of G6PD deficiency
  • Systolic blood pressure <110 mmHg or diastolic blood pressure <40 mmHg;
  • Contraindications to a cardiac MRI: (a) Central nervous system aneurysm clips; (b) Implanted neural stimulators; (c) Implanted cardiac pacemaker or defibrillator; (d) Cochlear implant; (e) Ocular foreign body (e.g. metal shavings); (f) Other implanted medical devices: (e.g. drug infusion ports); (g) Insulin pump; (h) Metal shrapnel or bullet; (i) Claustrophobia; (j) Extreme obesity rendering the patient unable to fit into narrow-bore scanners; (k) Unwillingness of the patient to undergo a cardiac MRI.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02791906


Contacts
Contact: Katherine Crockett 215-349-8076 Katherine.Crockett@uphs.upenn.edu
Contact: James Gordon 215-615-2351 James.Gordon@uphs.upenn.edu

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Katherine Crockett    215-349-8076    Katherine.Crockett@uphs.upenn.edu   
Contact: James Gordon    215-615-2351    James.Gordon@uphs.upenn.edu   
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Julio Chirinos, MD, PhD University of Pennsylvania

Responsible Party: Julio A. Chirinos, Principal Investigator, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02791906     History of Changes
Other Study ID Numbers: 823665
First Posted: June 7, 2016    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: September 2018

Keywords provided by Julio A. Chirinos, University of Pennsylvania:
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

Additional relevant MeSH terms:
Renal Insufficiency, Chronic
Kidney Diseases
Renal Insufficiency
Urologic Diseases
Vitamins
Ascorbic Acid
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents