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

University of Michigan

Status: Completed

Conditions: Tricuspid Atresia; Hypoplastic Left Heart Syndrome; Fontan Procedure

Treatments: Dietary Supplement: Placebo; Dietary Supplement: Vitamin C

Study type: Interventional

Funder types: Other

Identifiers

NCT00974025

HUM00029464

Details and patient eligibility

About

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.

Full 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.

Enrollment: 53 patients

Sex: All

Ages: 8 to 25 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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53 participants in 2 patient groups, including a placebo group

Vitamin C

Experimental group

Description:

High-dose Vitamin C in 4 age-based doses will be given in two-daily doses for four weeks

Treatment:

Dietary Supplement: Vitamin C

Placebo

Placebo Comparator group

Description:

Placebo will be given in two-daily doses for four weeks

Treatment:

Dietary Supplement: Placebo