Renal Insufficiency, ChronicPhase 2NCT02791906
Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease
A Phase 2 study testing ISMN and Vitamin C in people with Renal Insufficiency, Chronic, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Insufficiency, Chronic
- What is being tested?
- ISMN and Vitamin C
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to Mar 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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 glucose-6-phosphate dehydrogenase (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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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.
Read the 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 sustained release isosorbide mononitrate (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.
- Conditions
- Renal Insufficiency, Chronic
- Being tested
- ISMN, Vitamin C
- 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
- Medical subject headings
- Renal Insufficiency, Chronic, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISMNDrug
Vitamin CDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| ISMN Only | Experimental | Patients receive only ISMN Receives: Drug: ISMN |
| ISMN AND Vitamin C | Experimental | Patients receive both ISMN and Vitamin C Receives: Drug: ISMN; Dietary Supplement: Vitamin C |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured at Baseline Visit and 24 Week Visit
Secondary outcomes (4)
Changes in Diffuse Myocardial Fibrosis
Myocardial ECV was assessed using a modified Look-Locker inversion recovery sequence to assess T1 times before and following the IV administration of gadolinium contrast in a mid-ventricular short-axis slice. Parameters for modified Look-Locker inversion recovery were: field of view=340mm2; matrix size=144×192; slice thickness=6mm; repetition time=2.4ms; echo time=1.18ms; flip angle=30 degrees, bandwidth=1000 Hz/pixel, integrated parallel acquisition techniques=2. Myocardial T1measurements were performed before and at several time points (5, 10, 15, and 20-40 min) post-gadolinium administration. Modified Look-Locker inversion recovery was performed with a 5-3-3 schema with (2 inversions, 5 echo times after inversion 1, 3 T1 recovery heartbeats, and 3 echo times after inversion 2). All T1 measurements were used to compute lambda (the myocardium-blood partition coefficient) as the slope of the myocardial 1/T1 over the blood 1/T1 change, by linear regression.
Measured: Measured at Baseline Visit and 24 Week Visit
Changes in Myocardial Systolic and Diastolic Function
Variability in changes in myocardial function with ISMN administration, assessed via systolic longitudinal strain (measured with tissue tracking MRI) with adequate data for tissue tracking. Strain is the shortening during contraction, expressed as a promotion of the end-diastolic myocardial length. Shortening is indicated by a negative value. Strain is a unit-less metric and is thus expressed in %. A change with negative sign indicates more pronounced shortening of baseline compared to 6 months; a change with positive sign indicates less pronounced shortening during contraction.
Measured: Measured at Baseline Visit and 24 visits
Pulse Wave Reflection Magnitude
Measured by arterial tonometry and echocardiography. The data reflects estimated changes in each group utilizing all available measurements, collected at all timepoints (baseline visit and weeks 1, 2, 3, 12, and 24 visits). Numbers are estimated changes in each group utilizing available measurements. The change represents the absolute change in the ratio of backward to forward wave amplitudes, multiplied by 100.
Measured: Measured between Baseline Visit-Week 24
Aerobic Capacity
Variability in changes in aerobic capacity (peak oxygen consumption during maximal supine bicycle exercise test)
Measured: Change from Baseline at Week 24 reported
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2016 (estimated)
- Study startMay 2016
- Primary completionMar 2019
- Study completionMar 2019
Why it stopped: lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal Insufficiency, ChronicStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Julio A. Chirinos, University of Pennsylvania
- Investigators
- Julio Chirinos, MD, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02791906
- Sponsor's protocol ID
- 823665
- Status last verified
- Jul 2020
- First submitted
- 26 May 2016
- Last updated
- 13 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT02791906
- Acronym / sponsor ID
- 823665
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of funding
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 7 Jun 2016 (estimated)
- Results
- Posted 13 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 sustained release isosorbide mononitrate (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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ISMN Only | Experimental | Drug: ISMNPatients receive only ISMN |
| ISMN AND Vitamin C | Experimental | Drug: ISMN, Dietary Supplement: Vitamin CPatients receive both ISMN and Vitamin C |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISMN | Drug | ISMN AND Vitamin C, ISMN Only |
| Vitamin C | Dietary supplement | ISMN AND Vitamin C |
Primary outcome
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, outcomes reflect the change, in grams
4 secondary outcomes
Changes in Diffuse Myocardial Fibrosis
Time frame: Measured at Baseline Visit and 24 Week Visit
Changes in Myocardial Systolic and Diastolic Function
Time frame: Measured at Baseline Visit and 24 visits
Pulse Wave Reflection Magnitude
Time frame: Measured between Baseline Visit-Week 24
Aerobic Capacity
Time frame: Change from Baseline at Week 24 reported
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julio Chirinos, MD, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ISMN and Vitamin C in people with Renal Insufficiency, Chronic, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in LV Mass (time frame: Measured at Baseline Visit and 24 Week Visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2020.