Clinical trial NCT03404258: ET1 Concentration, Metabolic Pathway Activation, and Pulmonary Blood Flow in Infants Undergoing Superior Cavo-Pulmonary Anastomosis
Official title: ET1 Concentration, Metabolic Pathway Activation, and Pulmonary Blood Flow in Infants Undergoing Superior Cavo-Pulmonary Anastomosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Single-ventricle
Pulmonary Vascular Resistance Abnormality
Superior Cavo-Pulmonary Anastomosis
Endothelin
Metabolomics
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2018-01-19
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Infants with single ventricle heart disease undergoing trans-catheter evaluation in anticipation of superior cavo-pulmonary anastomosis.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference in ET1 concentration between controls, study patients at pre-SCPA catheterization, and study patients in the post-operative period.
timeFrame: 48 hours post-operatively
measure: Difference in metabolomics profile between controls, study patients at pre-SCPA catheterization, and study patients in the post-operative period.
timeFrame: 48 hours post-operatively
Secondary outcomes:
measure: Association between ET1 concentration at pre-SCPA catheterization in study patients and clinical metrics of pre-operative pulmonary adequacy.
timeFrame: 48 hours post-operatively
measure: Association between metabolomics profile in study patients and clinical metrics of pre-operative pulmonary adequacy.
timeFrame: 48 hours post-operatively
Other outcomes:
Locations:
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Benjamin Frank, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.