Back to resultsImproving Right Ventricular Function in Young Adults Born Preterm
Primary Purpose
Infant,Premature
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pulmonary Function Testing
Electrocardiogram
Cardiac Magnetic Resonance Imaging
Metoprolol
Sildenafil
Sponsored by
About this trial
This is an interventional treatment trial for Infant,Premature focused on measuring premature adults, premature, premature cardiac function, MRI, sildenafil, metoprolol, CMR
Eligibility Criteria
Inclusion Criteria:
- Provision of signed and dated informed consent form
- Male or female aged 18-35
History of preterm birth (either a or b):
- Participant in the Newborn Lung Project (birth year 1988-1991, birth weight <1500 g)
- Non-NLP participant, with birth weight <1500 g and gestational age 32 weeks or less, verified by medical records
Exclusion Criteria:
- Pregnant or lactating
Use of prescribed medications that would interfere with study medications
- Sildenafil: Use of phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil), nitrates, soluble guanylate cyclase inhibitor (riociguat) within 48 hours of study visit
- Metoprolol: Use of nodal blocking agents including beta blockers, non-dihydropyridine calcium channel blockers (i.e. diltiazem), and anti-arrhythmics (i.e. amiodarone)
Presence of known comorbidities for which these therapeutic interventions would be contraindicated:
- Moderate to severe heart failure
- Severe bradycardia (heart rate <45), or second or third-degree heart block
- Systolic blood pressure <90 mmHg or >190 mmHg
- Angina
- Severe peripheral arterial circulatory disorders
- History of severe bronchospasm
- Presence of any implanted device incompatible with CMR imaging
- Known allergic or hypersensitivity reaction to components of the study medications
- Any other reason for which the investigator deems a subject unsafe or inappropriate for study participation.
Sites / Locations
- University of Wisconsin-Madison School of Medicine and Public Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Sildenafil followed by Metoprolol
Metoprolol followed by Sildenafil
Arm Description
Young adults born premature, recruited either from the National Lung Project Cohort or the general public, will undergo Cardiac Magnetic Resonance Imaging before and after medication administration. This will occur twice, on two separate visits. Subjects will be given sildenafil in between imaging scans at one visit, and will receive intravenous metoprolol in between scans at next visit. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out. Subjects will also undergo pulmonary function testing and electrocardiogram.
Young adults born premature, recruited either from the National Lung Project Cohort or the general public, will undergo Cardiac Magnetic Resonance Imaging before and after medication administration. This will occur twice, on two separate visits. Subjects will be given metoprolol in between imaging scans at one visit, and will receive intravenous sildenafil in between scans at next visit. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out. Subjects will also undergo pulmonary function testing and electrocardiogram.
Outcomes
Primary Outcome Measures
Right Ventricular Energetic Efficiency Pre and Post Metoprolol
To characterize energy efficiency, the total Kinetic Energy across the cardiac cycle is normalized to right ventricular end-diastolic volume and left ventricular end-diastolic volume, respectively. Analysis will be completed in blinded fashion. Two imaging scans will be done - one pre and one post Metoprolol intervention. Total time from Pre-intervention scan till post intervention scan may take up to 2 hours.
Right Ventricular Energetic Efficiency Pre and Post Sildenafil
To characterize energy efficiency, the total Kinetic Energy across the cardiac cycle is normalized to right ventricular end-diastolic volume and left ventricular end-diastolic volume, respectively. Analysis will be completed in blinded fashion. Two imaging scans will be done - one pre and one post Sildenafil intervention. Total time from Pre-intervention scan till post intervention scan may take up to 2 hours.
Secondary Outcome Measures
Left Ventricular Energetic Efficiency Pre and Post Metoprolol
Kinetic energy (from 4D flow) normalized to ventricular volume (from MRI). Participants will receive intravenous metoprolol in between scans.
Right Ventricular Ejection Fraction Pre and Post Metoprolol
Participants will receive intravenous metoprolol in between scans.
Right Ventricular Stroke Volume Pre and Post Metoprolol
Participants will receive intravenous metoprolol in between scans.
Right Ventricular Systolic Volume Pre and Post Metoprolol
Participants will receive intravenous metoprolol in between scans.
Right Ventricular Diastolic Volume Pre and Post Metoprolol
Participants will receive intravenous metoprolol in between scans.
Left Ventricular Ejection Fraction Pre and Post Metoprolol
Participants will receive intravenous metoprolol in between scans.
Left Ventricular Stroke Volume Pre and Post Metoprolol
Participants will receive intravenous metoprolol in between scans.
Left Ventricular Systolic Volume Pre and Post Metoprolol
Participants will receive intravenous metoprolol in between scans.
Left Ventricular Diastolic Volume Pre and Post Metoprolol
Participants will receive intravenous metoprolol in between scans.
Left Ventricular Energetic Efficiency Pre and Post Sildenafil
Kinetic energy (from 4D flow) normalized to ventricular volume (from MRI). Participants will be given sildenafil in between imaging scans.
Right Ventricular Ejection Fraction Pre and Post Sildenafil
Participants will be given sildenafil in between imaging scans. The term "ejection fraction" refers to the percentage of blood that's pumped out of a filled ventricle with each heartbeat.
Right Ventricular Stroke Volume Pre and Post Sildenafil
Participants will be given sildenafil in between imaging scans.
Right Ventricular Systolic Volume Pre and Post Sildenafil
Participants will be given sildenafil in between imaging scans.
Right Ventricular Diastolic Volume Pre and Post Sildenafil
Participants will be given sildenafil in between imaging scans.
Left Ventricular Ejection Fraction Pre and Post Sildenafil
Participants will be given sildenafil in between imaging scans.
Left Ventricular Stroke Volume Pre and Post Sildenafil
Participants will be given sildenafil in between imaging scans.
Left Ventricular Systolic Volume Pre and Post Sildenafil
Participants will be given sildenafil in between imaging scans.
Left Ventricular Diastolic Volume Pre and Post Sildenafil
Participants will be given sildenafil in between imaging scans.
Full Information
NCT ID
NCT03696758
First Posted
October 3, 2018
Last Updated
February 24, 2021
Sponsor
University of Wisconsin, Madison
Collaborators
National Center for Advancing Translational Sciences (NCATS)
1. Study Identification
Unique Protocol Identification Number
NCT03696758
Brief Title
Improving Right Ventricular Function in Young Adults Born Preterm
Official Title
Improving Right Ventricular Function in Young Adults Born Preterm: A Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
October 30, 2018 (Actual)
Primary Completion Date
February 24, 2020 (Actual)
Study Completion Date
February 24, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Center for Advancing Translational Sciences (NCATS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this research is to evaluate the short-term effects of sildenafil and metoprolol on heart function in young adults born premature.
Detailed Description
The purpose of this study is to evaluate the short-term therapeutic effects of sildenafil and metoprolol on right ventricular function in young adults born premature using novel 4-Dimensional flow Cardiac Magnetic Resonance Imaging.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infant,Premature
Keywords
premature adults, premature, premature cardiac function, MRI, sildenafil, metoprolol, CMR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Young adults born premature, recruited either from the National Lung Project Cohort or the general public, will undergo Cardiac Magnetic Resonance Imaging before and after medication administration. This will occur twice, on two separate visits. Subjects will be given sildenafil in between imaging scans at one visit, and will receive intravenous metoprolol in between scans at a separate visit. These visits can occur in either order. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out.
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sildenafil followed by Metoprolol
Arm Type
Experimental
Arm Description
Young adults born premature, recruited either from the National Lung Project Cohort or the general public, will undergo Cardiac Magnetic Resonance Imaging before and after medication administration. This will occur twice, on two separate visits. Subjects will be given sildenafil in between imaging scans at one visit, and will receive intravenous metoprolol in between scans at next visit. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out. Subjects will also undergo pulmonary function testing and electrocardiogram.
Arm Title
Metoprolol followed by Sildenafil
Arm Type
Experimental
Arm Description
Young adults born premature, recruited either from the National Lung Project Cohort or the general public, will undergo Cardiac Magnetic Resonance Imaging before and after medication administration. This will occur twice, on two separate visits. Subjects will be given metoprolol in between imaging scans at one visit, and will receive intravenous sildenafil in between scans at next visit. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out. Subjects will also undergo pulmonary function testing and electrocardiogram.
Intervention Type
Procedure
Intervention Name(s)
Pulmonary Function Testing
Intervention Description
Subjects will undergo spirometry, Plethysmography, and diffusion capacity.
Intervention Type
Procedure
Intervention Name(s)
Electrocardiogram
Intervention Description
Subjects will undergo an electrocardiogram to ensure sinus rhythm
Intervention Type
Procedure
Intervention Name(s)
Cardiac Magnetic Resonance Imaging
Intervention Description
Subjects will undergo positron magnetic resonance imaging to detect images of the heart
Intervention Type
Drug
Intervention Name(s)
Metoprolol
Other Intervention Name(s)
Lopressor, Metolar XR
Intervention Description
Subjects will receive intravenous metoprolol. Dose titrated 1-5 mg every 2 minutes to achieve goal heart rate of 55-65 beats per minute, or for subjects with a resting heart rate already at goal, titrated to achieve a 10-15% reduction in heart rate.
Intervention Type
Drug
Intervention Name(s)
Sildenafil
Other Intervention Name(s)
Revatio
Intervention Description
Subjects will receive a 50 milligram tablet of sildenafil (to be taken orally)
Primary Outcome Measure Information:
Title
Right Ventricular Energetic Efficiency Pre and Post Metoprolol
Description
To characterize energy efficiency, the total Kinetic Energy across the cardiac cycle is normalized to right ventricular end-diastolic volume and left ventricular end-diastolic volume, respectively. Analysis will be completed in blinded fashion. Two imaging scans will be done - one pre and one post Metoprolol intervention. Total time from Pre-intervention scan till post intervention scan may take up to 2 hours.
Time Frame
up to 2 hours
Title
Right Ventricular Energetic Efficiency Pre and Post Sildenafil
Description
To characterize energy efficiency, the total Kinetic Energy across the cardiac cycle is normalized to right ventricular end-diastolic volume and left ventricular end-diastolic volume, respectively. Analysis will be completed in blinded fashion. Two imaging scans will be done - one pre and one post Sildenafil intervention. Total time from Pre-intervention scan till post intervention scan may take up to 2 hours.
Time Frame
up to 2 hours
Secondary Outcome Measure Information:
Title
Left Ventricular Energetic Efficiency Pre and Post Metoprolol
Description
Kinetic energy (from 4D flow) normalized to ventricular volume (from MRI). Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Right Ventricular Ejection Fraction Pre and Post Metoprolol
Description
Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Right Ventricular Stroke Volume Pre and Post Metoprolol
Description
Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Right Ventricular Systolic Volume Pre and Post Metoprolol
Description
Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Right Ventricular Diastolic Volume Pre and Post Metoprolol
Description
Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Left Ventricular Ejection Fraction Pre and Post Metoprolol
Description
Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Left Ventricular Stroke Volume Pre and Post Metoprolol
Description
Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Left Ventricular Systolic Volume Pre and Post Metoprolol
Description
Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Left Ventricular Diastolic Volume Pre and Post Metoprolol
Description
Participants will receive intravenous metoprolol in between scans.
Time Frame
up to 2 hours
Title
Left Ventricular Energetic Efficiency Pre and Post Sildenafil
Description
Kinetic energy (from 4D flow) normalized to ventricular volume (from MRI). Participants will be given sildenafil in between imaging scans.
Time Frame
up to 2 hours
Title
Right Ventricular Ejection Fraction Pre and Post Sildenafil
Description
Participants will be given sildenafil in between imaging scans. The term "ejection fraction" refers to the percentage of blood that's pumped out of a filled ventricle with each heartbeat.
Time Frame
up to 2 hours
Title
Right Ventricular Stroke Volume Pre and Post Sildenafil
Description
Participants will be given sildenafil in between imaging scans.
Time Frame
up to 2 hours
Title
Right Ventricular Systolic Volume Pre and Post Sildenafil
Description
Participants will be given sildenafil in between imaging scans.
Time Frame
up to 2 hours
Title
Right Ventricular Diastolic Volume Pre and Post Sildenafil
Description
Participants will be given sildenafil in between imaging scans.
Time Frame
up to 2 hours
Title
Left Ventricular Ejection Fraction Pre and Post Sildenafil
Description
Participants will be given sildenafil in between imaging scans.
Time Frame
up to 2 hours
Title
Left Ventricular Stroke Volume Pre and Post Sildenafil
Description
Participants will be given sildenafil in between imaging scans.
Time Frame
up to 2 hours
Title
Left Ventricular Systolic Volume Pre and Post Sildenafil
Description
Participants will be given sildenafil in between imaging scans.
Time Frame
up to 2 hours
Title
Left Ventricular Diastolic Volume Pre and Post Sildenafil
Description
Participants will be given sildenafil in between imaging scans.
Time Frame
up to 2 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of signed and dated informed consent form
Male or female aged 18-35
History of preterm birth (either a or b):
Participant in the Newborn Lung Project (birth year 1988-1991, birth weight <1500 g)
Non-NLP participant, with birth weight <1500 g and gestational age 32 weeks or less, verified by medical records
Exclusion Criteria:
Pregnant or lactating
Use of prescribed medications that would interfere with study medications
Sildenafil: Use of phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil), nitrates, soluble guanylate cyclase inhibitor (riociguat) within 48 hours of study visit
Metoprolol: Use of nodal blocking agents including beta blockers, non-dihydropyridine calcium channel blockers (i.e. diltiazem), and anti-arrhythmics (i.e. amiodarone)
Presence of known comorbidities for which these therapeutic interventions would be contraindicated:
Moderate to severe heart failure
Severe bradycardia (heart rate <45), or second or third-degree heart block
Systolic blood pressure <90 mmHg or >190 mmHg
Angina
Severe peripheral arterial circulatory disorders
History of severe bronchospasm
Presence of any implanted device incompatible with CMR imaging
Known allergic or hypersensitivity reaction to components of the study medications
Any other reason for which the investigator deems a subject unsafe or inappropriate for study participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kara N Goss, MD
Organizational Affiliation
University of Wisconsin-Madison School of Medicine and Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin-Madison School of Medicine and Public Health
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Improving Right Ventricular Function in Young Adults Born Preterm
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