Clinical trial NCT03322345: Characterizing the Effect of Dopamine on Markers of Lymph Re-circulation in Fontan-associated Protein-losing Enteropathy
Official title: Characterizing the Effect of Dopamine on Markers of Lymph Re-circulation in Fontan-associated Protein-losing Enteropathy
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Dopamine
Protein-Losing Enteropathies
Lymphatic System
Lymph
Catecholamine
Single-ventricle
Congenital Heart Disease
Keywords: lymph flow
Fontan
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2017-10-26
Enrollment: 24
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be prospective cohort of patients who have undergone Fontan surgery and are currenty followed within the University of Michigan Congenital Heart Center. The target populations are patients with protein losing enteropathy (PLE) that are having increased disease symptoms requiring additional treatment. Those that have PLE refractory to other treatments and require the addition of continuous dopamine infusion to their treatment regimen will be recruited to the dopamine group. Those that have PLE worsening that require the addition of other treatments except the initiation of continuous dopamine infusion will be recruited to the control group.

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.

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

Primary outcomes:
measure: Change in CD4 counts
timeFrame: Baseline to 6 months
measure: Change in fatty acid profile
timeFrame: Baseline to 6 months
measure: Change in vitamin D3
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Change in albumin infusion requirements
timeFrame: Baseline to 6 months
measure: Change in IVIG infusion requirements
timeFrame: Baseline to 6 months
measure: Change in PLE symptoms
timeFrame: baseline to 6 months
measure: Change in quality of life
timeFrame: baseline to 6 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
Study officials:
affiliation: University of Michigan Division of Pediatric Cardiology
name: Kurt Schumacher, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan Division of Pediatric Cardiology
name: Joshua Meisner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: