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

Hypoplastic Left Heart Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00974025
• Other study ID #: HUM00029464
• Status: Completed
• Phase: N/A
• First received: September 9, 2009
• Last updated: May 31, 2017
• Start date: June 2009
• Est. completion date: March 2010

Study information

• Verified date: May 2017
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: March 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Fontan Procedure
• Hypoplastic Left Heart Syndrome
• Tricuspid Atresia

Intervention

Dietary Supplement:
• Vitamin C
High-dose Vitamin C will be administered in 4 age-based dosing groups
• Placebo
Placebo will be administered twice daily for four weeks

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Griese-Hutchinson Champions for Children's Hearts Investigator Award

Country where clinical trial is conducted

United States, 

References & Publications (1)

Goldstein BH, Golbus JR, Sandelin AM, Warnke N, Gooding L, King KK, Donohue JE, Gurney JG, Goldberg CS, Rocchini AP, Charpie JR. Usefulness of peripheral vascular function to predict functional health status in patients with Fontan circulation. Am J Cardi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in peak oxygen consumption (from baseline to post-study drug testing)		4 weeks
Secondary	Oxygen Pulse		4 weeks
Secondary	Peak Work		4 weeks
Secondary	Endo-PAT score		4 weeks
Secondary	Framingham Modified Endothelial Function Score		4 weeks
Secondary	PedsQL 4.0 - quality of life assessment		4 weeks
Secondary	BNP		4 weeks