Trial Outcomes & Findings for Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease (NCT NCT02791906)

NCT ID: NCT02791906

Last Updated: 2020-08-13

Results Overview

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

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: Measured at Baseline Visit and 24 Week Visit
• Results posted on: 2020-08-13

Participant Flow

Screening was performed from electronic medical records searcesh for potential study participants, followed by manual review.

After assessing subjects for eligibility via electronic health record reviews (n=529), 522 were excluded due to not meeting inclusion/exclusion criteria (n=506), not being interested in participating upon telephone interview (n=3) and various other reasons (inability to contact, inability to exercise, scheduling difficulties; n=13).

Participant milestones

Measure	ISMN Only Patients receive only ISMN ISMN	ISMN AND Vitamin C Patients receive both ISMN and Vitamin C ISMN Vitamin C
Overall Study STARTED	4	3
Overall Study COMPLETED	2	2
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease

Baseline characteristics by cohort

Measure	ISMN Only n=4 Participants Patients receive only ISMN ISMN	ISMN AND Vitamin C n=3 Participants Patients receive both ISMN and Vitamin C ISMN Vitamin C	Total n=7 Participants Total of all reporting groups
Age, Continuous	64.75 years STANDARD_DEVIATION 10.65 • n=5 Participants	64 years STANDARD_DEVIATION 4.36 • n=7 Participants	64.43 years STANDARD_DEVIATION 7.96 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	ISMN Only n=2 Participants Patients receive only ISMN ISMN	ISMN AND Vitamin C n=2 Participants Patients receive both ISMN and Vitamin C ISMN Vitamin C
Change in LV Mass	24.95 grams Standard Deviation 31.5	-10.4 grams Standard Deviation 1.26

SECONDARY outcome

Timeframe: Measured at Baseline Visit and 24 Week Visit

Population: Patients who had measurements at baseline and 24 weeks.

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.

Outcome measures

Measure	ISMN Only n=2 Participants Patients receive only ISMN ISMN	ISMN AND Vitamin C n=2 Participants Patients receive both ISMN and Vitamin C ISMN Vitamin C
Changes in Diffuse Myocardial Fibrosis	-0.68 % of myocardial tissue composed of ECV Standard Deviation 4.56	2.12 % of myocardial tissue composed of ECV Standard Deviation 2.99

SECONDARY outcome

Timeframe: Measured at Baseline Visit and 24 visits

Population: patients who underwent measurements at baseline and 24 weeks

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.

Outcome measures

Measure	ISMN Only n=2 Participants Patients receive only ISMN ISMN	ISMN AND Vitamin C n=1 Participants Patients receive both ISMN and Vitamin C ISMN Vitamin C
Changes in Myocardial Systolic and Diastolic Function	-3.95 Percent shortening Standard Deviation 9.67	7.23 Percent shortening Standard Deviation 0

SECONDARY outcome

Timeframe: Measured between Baseline Visit-Week 24

Population: participants with measurements available at baseline and 24 weeks

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.

Outcome measures

Measure	ISMN Only n=2 Participants Patients receive only ISMN ISMN	ISMN AND Vitamin C n=2 Participants Patients receive both ISMN and Vitamin C ISMN Vitamin C
Pulse Wave Reflection Magnitude	0.47 % of change in magnitude Standard Deviation 6.11	-2.28 % of change in magnitude Standard Deviation 8.77

SECONDARY outcome

Timeframe: Change from Baseline at Week 24 reported

Population: Only 3 subjects had sufficient data to compute a change from baseline, 1 in the ISMN only arm and 2 in the ISMN + Vit C arm. Below are the results of the data that was analyzed for those subjects.

Variability in changes in aerobic capacity (peak oxygen consumption during maximal supine bicycle exercise test)

Outcome measures

Measure	ISMN Only n=1 Participants Patients receive only ISMN ISMN	ISMN AND Vitamin C n=2 Participants Patients receive both ISMN and Vitamin C ISMN Vitamin C
Aerobic Capacity	0.05732 L of O2 consumed/ minute Standard Deviation 0	0.32813 L of O2 consumed/ minute Standard Deviation 0.49521

Adverse Events

ISMN Only

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

ISMN AND Vitamin C

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	ISMN Only n=4 participants at risk Monotherapy with isosorbide mononitrate	ISMN AND Vitamin C n=3 participants at risk Combination therapy with isosorbide mononitrate and vitamin C
Infections and infestations Urosepsis requiring hospitalization	0.00% 0/4 • 6 months	33.3% 1/3 • Number of events 1 • 6 months

Other adverse events

Measure	ISMN Only n=4 participants at risk Monotherapy with isosorbide mononitrate	ISMN AND Vitamin C n=3 participants at risk Combination therapy with isosorbide mononitrate and vitamin C
Renal and urinary disorders Worsening renal AKI + Hyperkalemia	25.0% 1/4 • Number of events 1 • 6 months	0.00% 0/3 • 6 months
Cardiac disorders 2n degree AV block	0.00% 0/4 • 6 months	33.3% 1/3 • Number of events 1 • 6 months
Skin and subcutaneous tissue disorders Skin rash	75.0% 3/4 • Number of events 4 • 6 months	33.3% 1/3 • Number of events 1 • 6 months
Renal and urinary disorders Hypokalemia	25.0% 1/4 • Number of events 1 • 6 months	0.00% 0/3 • 6 months
General disorders fatigue	0.00% 0/4 • 6 months	33.3% 1/3 • Number of events 1 • 6 months
Nervous system disorders Drowsiness/dizziness/lightheadedness	50.0% 2/4 • Number of events 3 • 6 months	33.3% 1/3 • Number of events 1 • 6 months
General disorders dry mouth	25.0% 1/4 • Number of events 1 • 6 months	33.3% 1/3 • Number of events 1 • 6 months
Cardiac disorders Ankle swelling	25.0% 1/4 • Number of events 1 • 6 months	0.00% 0/3 • 6 months
General disorders Nausea	25.0% 1/4 • Number of events 1 • 6 months	66.7% 2/3 • Number of events 2 • 6 months
General disorders Headache	0.00% 0/4 • 6 months	66.7% 2/3 • Number of events 3 • 6 months
General disorders Balance problems	0.00% 0/4 • 6 months	33.3% 1/3 • Number of events 1 • 6 months
Gastrointestinal disorders Heart burn	0.00% 0/4 • 6 months	33.3% 1/3 • Number of events 1 • 6 months
General disorders Sleep	0.00% 0/4 • 6 months	33.3% 1/3 • Number of events 1 • 6 months
General disorders Sweating	0.00% 0/4 • 6 months	66.7% 2/3 • Number of events 2 • 6 months

Additional Information

Associate Professor

University of Pennsylvania

Phone: 2152007779

Email: julio.chirinos@uphs.upenn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place