Fontan Procedure, Hypoplastic Left Heart Syndrome, Tricuspid Atresia
Conditions
Brief summary
In this study, investigators will evaluate the effect of vitamin C on endothelial function, exercise tolerance and quality of life in patients with a single ventricle who have been palliated to Fontan physiology. The hypothesis is that vitamin C will result in improved exercise tolerance and endothelial function in patients who have undergone the Fontan operation, compared to placebo.
Detailed description
Recent evidence suggests that after Fontan operation, single ventricle patients have impaired function of the vascular endothelium due in part to abnormalities in nitric oxide signaling. Endothelial dysfunction may contribute to the development of congestive heart failure and exercise intolerance that have been well-documented in Fontan patients. Therapeutic interventions to improve endothelial function in adults with heart failure have mainly focused on increasing the synthesis or decreasing the degradation of nitric oxide. We propose a randomized, prospective, placebo-controlled trial of vitamin C, an antioxidant that protects NO deactivation, in subjects with single ventricular anatomy after Fontan palliation. The specific aims of this study are to compare NO signaling, endothelial function and exercise capacity in Fontan subjects to that of a control group that is frequency-matched to case subjects by age and sex, and to assess NO signaling, endothelial function and exercise capacity in Fontan subjects after 4 weeks of oral vitamin C (or placebo) therapy. These results have particular importance because improving the endothelial response in Fontan patients has the potential to reduce the risk of developing congestive heart failure and improve exercise capacity. Furthermore, assessing endothelial function and the effects of therapies aimed at improving vascular health may be generalizable to many other chronic pediatric conditions associated with increased cardiovascular risk such as obesity, diabetes mellitus, and hypertension.
Interventions
DIETARY_SUPPLEMENTVitamin C
High-dose Vitamin C will be administered in 4 age-based dosing groups
DIETARY_SUPPLEMENTPlacebo
Placebo will be administered twice daily for four weeks
Sponsors
Griese-Hutchinson Champions for Children's Hearts Investigator Award
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 25 Years
Healthy volunteers
Yes
Inclusion criteria
* 8-25 years of age * Fontan-palliated patient
Exclusion criteria
* New York Heart Association (NYHA) classes III or IV * Diabetes mellitus * Family history of premature coronary artery disease * Use of Sildenafil or other pulmonary artery vasodilators * Prior cardiac arrest (outside the first 24-hours postoperatively) * Life-threatening dysrhythmias * Severe ventricular dysfunction * Severe AV valve regurgitation * Pregnancy * Severe renal or hepatic impairment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in peak oxygen consumption (from baseline to post-study drug testing) | 4 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Peak Work | 4 weeks |
| Endo-PAT score | 4 weeks |
| Oxygen Pulse | 4 weeks |
| PedsQL 4.0 - quality of life assessment | 4 weeks |
| BNP | 4 weeks |
| Framingham Modified Endothelial Function Score | 4 weeks |
Countries
United States
Outcome results
None listed