Impact of Vitamin C on Endothelial Function and Exercise Capacity in Fontan-Palliated Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Vitamin C May Improve Endothelial Function and Exercise Capacity in Functional Single Ventricle Patients After Fontan Palliation

Conditions
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Fontan Procedure, Hypoplastic Left Heart Syndrome, Tricuspid Atresia

Intervention / Treatment
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* Dietary Supplement: Vitamin C
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin C<br>High-dose Vitamin C in 4 age-based doses will be given in two-daily doses for four weeks | Dietary Supplement: Vitamin C<br>* High-dose Vitamin C will be administered in 4 age-based dosing groups<br>|
| Placebo Comparator: Placebo<br>Placebo will be given in two-daily doses for four weeks | Dietary Supplement: Placebo<br>* Placebo will be administered twice daily for four weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in peak oxygen consumption (from baseline to post-study drug testing) |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygen Pulse |  | 4 weeks | 
| Peak Work |  | 4 weeks | 
| Endo-PAT score |  | 4 weeks | 
| Framingham Modified Endothelial Function Score |  | 4 weeks | 
| PedsQL 4.0 - quality of life assessment |  | 4 weeks | 
| BNP |  | 4 weeks |