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

Not Applicable

Completed

• Conditions: Fontan Procedure; Hypoplastic Left Heart Syndrome; Tricuspid Atresia
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Vitamin C

• Registration Number: NCT00974025
• Lead Sponsor: University of Michigan

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.

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-09-09
• Study First Submitted QC: 2009-09-09
• Study First Posted: 2009-09-10
• Primary Completion: 2009-11
• Study Completion: 2010-03
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-31
• Last Update Posted: 2017-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change in peak oxygen consumption (from baseline to post-study drug testing)	4 weeks

Secondary Outcome Measures

Name	Time	Method
Framingham Modified Endothelial Function Score	4 weeks
BNP	4 weeks
Endo-PAT score	4 weeks
Peak Work	4 weeks
PedsQL 4.0 - quality of life assessment	4 weeks
Oxygen Pulse	4 weeks

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States