Improving Right Ventricular Function in Young Adults Born Preterm

Infant,Premature Clinical Trial

Official title:

Improving Right Ventricular Function in Young Adults Born Preterm: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03696758
• Other study ID #: 2018-0796
• Secondary ID: 1UL1TR002373-01A
• Status: Completed
• Phase: Phase 2
• Start date: October 30, 2018
• Est. completion date: February 24, 2020

Study information

• Verified date: February 2021
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: February 24, 2020
• Est. primary completion date: February 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Male or female aged 18-35

3. History of preterm birth (either a or b):

1. Participant in the Newborn Lung Project (birth year 1988-1991, birth weight <1500 g)

2. Non-NLP participant, with birth weight <1500 g and gestational age 32 weeks or less, verified by medical records

Exclusion Criteria:

1. Pregnant or lactating

2. Use of prescribed medications that would interfere with study medications

1. Sildenafil: Use of phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil), nitrates, soluble guanylate cyclase inhibitor (riociguat) within 48 hours of study visit

2. Metoprolol: Use of nodal blocking agents including beta blockers, non-dihydropyridine calcium channel blockers (i.e. diltiazem), and anti-arrhythmics (i.e. amiodarone)

3. Presence of known comorbidities for which these therapeutic interventions would be contraindicated:

1. Moderate to severe heart failure

2. Severe bradycardia (heart rate <45), or second or third-degree heart block

3. Systolic blood pressure <90 mmHg or >190 mmHg

4. Angina

5. Severe peripheral arterial circulatory disorders

6. History of severe bronchospasm

4. Presence of any implanted device incompatible with CMR imaging

5. Known allergic or hypersensitivity reaction to components of the study medications

6. Any other reason for which the investigator deems a subject unsafe or inappropriate for study participation.

Related Conditions & MeSH terms

• Infant,Premature
• Premature Birth

Intervention

Procedure:
• Pulmonary Function Testing
Subjects will undergo spirometry, Plethysmography, and diffusion capacity.
• Electrocardiogram
Subjects will undergo an electrocardiogram to ensure sinus rhythm
• Cardiac Magnetic Resonance Imaging
Subjects will undergo positron magnetic resonance imaging to detect images of the heart

Drug:
• Metoprolol
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.
• Sildenafil
Subjects will receive a 50 milligram tablet of sildenafil (to be taken orally)

Locations

Country	Name	City	State
United States	University of Wisconsin-Madison School of Medicine and Public Health	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Center for Advancing Translational Science (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 2 hours
Primary	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.	up to 2 hours
Secondary	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.	up to 2 hours
Secondary	Right Ventricular Ejection Fraction Pre and Post Metoprolol	Participants will receive intravenous metoprolol in between scans.	up to 2 hours
Secondary	Right Ventricular Stroke Volume Pre and Post Metoprolol	Participants will receive intravenous metoprolol in between scans.	up to 2 hours
Secondary	Right Ventricular Systolic Volume Pre and Post Metoprolol	Participants will receive intravenous metoprolol in between scans.	up to 2 hours
Secondary	Right Ventricular Diastolic Volume Pre and Post Metoprolol	Participants will receive intravenous metoprolol in between scans.	up to 2 hours
Secondary	Left Ventricular Ejection Fraction Pre and Post Metoprolol	Participants will receive intravenous metoprolol in between scans.	up to 2 hours
Secondary	Left Ventricular Stroke Volume Pre and Post Metoprolol	Participants will receive intravenous metoprolol in between scans.	up to 2 hours
Secondary	Left Ventricular Systolic Volume Pre and Post Metoprolol	Participants will receive intravenous metoprolol in between scans.	up to 2 hours
Secondary	Left Ventricular Diastolic Volume Pre and Post Metoprolol	Participants will receive intravenous metoprolol in between scans.	up to 2 hours
Secondary	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.	up to 2 hours
Secondary	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.	up to 2 hours
Secondary	Right Ventricular Stroke Volume Pre and Post Sildenafil	Participants will be given sildenafil in between imaging scans.	up to 2 hours
Secondary	Right Ventricular Systolic Volume Pre and Post Sildenafil	Participants will be given sildenafil in between imaging scans.	up to 2 hours
Secondary	Right Ventricular Diastolic Volume Pre and Post Sildenafil	Participants will be given sildenafil in between imaging scans.	up to 2 hours
Secondary	Left Ventricular Ejection Fraction Pre and Post Sildenafil	Participants will be given sildenafil in between imaging scans.	up to 2 hours
Secondary	Left Ventricular Stroke Volume Pre and Post Sildenafil	Participants will be given sildenafil in between imaging scans.	up to 2 hours
Secondary	Left Ventricular Systolic Volume Pre and Post Sildenafil	Participants will be given sildenafil in between imaging scans.	up to 2 hours
Secondary	Left Ventricular Diastolic Volume Pre and Post Sildenafil	Participants will be given sildenafil in between imaging scans.	up to 2 hours