Characterizing the Effect of Dopamine on Markers of Lymph Re-circulation in Fontan-associated Protein-losing Enteropathy

NCT ID: NCT03322345

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-04-09
• Study Completion Date: 2027-04-01

Brief Summary

Patients that have undergone a Fontan procedure (surgical correction for single ventricle congenital heart disease) may develop a complication known as protein-losing enteropathy (PLE). Some studies suggest PLE is primarily caused by impaired lymph flow. Use of continuous dopamine infusion can improve PLE. Evidence suggests the effect of dopamine may be through its effect on lymphatic function. This observational study looks at markers of lymph flow and PLE symptoms after treatment using dopamine and other standard therapies during disease exacerbations.

Detailed Description

For infants and newborns who have a heart defect at birth that leaves them with one functional ventricle, there is a series of surgeries that are required to allow survival. These surgeries ultimately lead to a common heart and great blood vessel circulation called a cavopulmonary anastomosis (Fontan). This has allowed for survival into adulthood from universally fatal outcome in infancy. However, the non-physiologic blood flow patterns of the Fontan pathway do result in certain complications, including protein losing enteropathy (PLE), which occurs in 3.7-13.4% of patients. PLE is denoted by the loss of protein, fats, and other key nutrients into the intestines, which can lead to significant morbidity. Recent evidence suggests that this is in part mediated by impaired flow of lymph from the intestines, which is carried by the parallel vascular system called the lymphatic system. Lymphatics return these nutrients and the fluid that leaks out of the blood vessels throughout the body back into the blood circulatory system by functioning as a series of pumps with one-way valves. While few treatments exist from PLE, evidence demonstrates continuous infusion of dopamine can help resolve PLE symptoms. Studies of isolated lymphatic vessels demonstrate that dopamine may increase the ability of lymphatic vessels to pump harder. This suggests the mechanism of action of dopamine in PLE is increasing the return of lymph in the non-physiologic blood flow patterns of Fontan patients. However, the link between improved return of lymph and improvement in PLE has not been established. Therefore, the investigators have designed this study to test whether markers of lymphatic flow and heart pump function improve when patients start continuous dopamine therapy (a standard practice at the University of Michigan for PLE). This involves tracking markers of lymphatic recirculation through serial testing of blood and monitoring of PLE symptoms before and after the start of dopamine and other standard of care therapies. From these data, the investigators will correlate the monitored changes in lymph recirculation with changes in PLE symptoms.

Conditions

Dopamine; Protein-Losing Enteropathies; Lymphatic System; Lymph; Catecholamine; Single-ventricle; Congenital Heart Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Dopamine Added

Patients with protein losing enteropathy (PLE) that have an exacerbation such that their treating physicians decide to add continuous dopamine infusion to their current therapies.

No interventions assigned to this group

No dopamine added (control)

Patients with protein losing enteropathy (PLE) that have an exacerbation such that their treating physicians decide to add new therapies to their current therapies but that do not require the addition of continuous dopamine infusion.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Males and females with Fontan physiology of any age
• Must have protein losing enteropathy with current worsening who require additional therapies
• Participant consent or parental/guardian consent and participant assent

Exclusion Criteria

• Patients with inflammatory bowel disease (i.e Crohn's, ulcerative colitis)
• Patients with systemic autoimmune disease (i.e. Systemic Lupus Erythematous)
• Patients with primary immunodeficiency syndromes
• Patients with nephrotic syndrome
• Patients with anemia
• Patients less than 31 pounds

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Joshua Meisner

Pediatric Cardiology Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kurt Schumacher, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Division of Pediatric Cardiology

Joshua Meisner, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Division of Pediatric Cardiology

Locations

University of Michigan Health System

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

LYMPH-DOPA-PLE

Identifier Type: -

Identifier Source: org_study_id