ET1 Concentration, Metabolic Pathway Activation, and Pulmonary Blood Flow in Infants Undergoing Superior Cavo-Pulmonary Anastomosis

This is a novel preliminary study of biomarkers of pathologic pre-operative pulmonary vascular development, elevated pre-operative Pulmonary Vascular Resistance Index (PVRi), and complications associated with decreased post-operative pulmonary blood flow in single ventricle patients undergoing superior cavo-pulmonary anastomosis (SCPA). The study will utilize a combined targeted and untargeted approach to both optimize translation of a promising existing biomarker and efficiently identify novel biomarkers and potential therapeutic targets in this population.

Study Overview

• Status: Active, not recruiting
• Conditions: Single-ventricle; Pulmonary Vascular Resistance Abnormality; Metabolomics; Superior Cavo-Pulmonary Anastomosis; Endothelin
• Intervention / Treatment: Other: Research Blood Sampling

Detailed Description

Overall Hypothesis: Endothelin-1 (ET1) and associated dysregulation of key metabolic pathways decrease pre-operative pulmonary blood vessel development and increase post-operative pulmonary blood vessel resistance leading to decreased pulmonary blood flow in patients undergoing SCPA.

For enrolled patients, collected data will include:

• 3 mL blood sample (x2) at pre-SCPA catheterization.
• 3 mL blood samples at 2, 24, and 48 hours post-operative.
• Urine sample pre-operatively and post-operatively
• Collection of otherwise-discarded operative tissue sample from the pulmonary artery.
• Collection of clinical data, demographic data, and results of routine, post-operative hemodynamic monitoring.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Infants with single ventricle heart disease undergoing trans-catheter evaluation in anticipation of superior cavo-pulmonary anastomosis.

Description

Inclusion Criteria:

• Congenital heart disease patients undergoing catheterization for pre-SPCA evaluation or undergoing SCPA without plans for cardiac catheterization (utilizing data from a previously performed clinical catheterization).
• All patients will have age from 31 days to 2 years.

Exclusion Criteria:

• Patients who will remain post-op with a pulsatile source of pulmonary blood flow in addition to the cavo-pulmonary anastomosis (so called "1.5 ventricle" repair) will be excluded.
• Due to limitations in acceptable sample blood volumes for research, patients with weight <4kg will be excluded.
• Patients will not be excluded on the basis of gender, ethnicity, genetic diagnosis, gestational age at birth, non-cardiac comorbidity, or pre-operative medication regimen.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study Patients; Infants between 1 month and 2 years of age undergoing evaluation for SCPA candidacy.	Other: Research Blood Sampling; Blood samples will be collected at specified time points and research assays will be performed.
Control Patients; Infants between 3 months and 12 months of age with no known cardio-pulmonary disease, no active infection, and no known genetic abnormality undergoing elective surgery for a non-cardiac indication.	Other: Research Blood Sampling; Blood samples will be collected at specified time points and research assays will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in ET1 concentration between controls, study patients at pre-SCPA catheterization, and study patients in the post-operative period.	48 hours post-operatively
Difference in metabolomics profile between controls, study patients at pre-SCPA catheterization, and study patients in the post-operative period.	48 hours post-operatively

Secondary Outcome Measures

Outcome Measure	Time Frame
Association between ET1 concentration at pre-SCPA catheterization in study patients and clinical metrics of pre-operative pulmonary adequacy.	48 hours post-operatively
Association between metabolomics profile in study patients and clinical metrics of pre-operative pulmonary adequacy.	48 hours post-operatively

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Benjamin Frank, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Frank BS, Khailova L, Silveira L, Mitchell MB, Morgan GJ, Hsieh EWY, DiMaria MV, Twite M, Klawitter J, Davidson JA. Proteomic profiling identifies key differences between inter-stage infants with single ventricle heart disease and healthy controls. Transl Res. 2021 Mar;229:24-37. doi: 10.1016/j.trsl.2020.10.001. Epub 2020 Oct 9.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2018
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 11, 2018
• First Submitted That Met QC Criteria: January 11, 2018
• First Posted (Actual): January 19, 2018

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Univentricular Heart
• Other Study ID Numbers: 17-0832

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No