Clinical trial NCT00974025: Impact of Vitamin C on Endothelial Function and Exercise Capacity in Fontan-Palliated Patients
Official title: Vitamin C May Improve Endothelial Function and Exercise Capacity in Functional Single Ventricle Patients After Fontan Palliation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fontan Procedure
Hypoplastic Left Heart Syndrome
Tricuspid Atresia
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Griese-Hutchinson Champions for Children's Hearts Investigator Award
First posted: 2009-09-10
Enrollment: 53
Sex: ALL
Minimum age (years): 8
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in peak oxygen consumption (from baseline to post-study drug testing)
timeFrame: 4 weeks
Secondary outcomes:
measure: Oxygen Pulse
timeFrame: 4 weeks
measure: Peak Work
timeFrame: 4 weeks
measure: Endo-PAT score
timeFrame: 4 weeks
measure: Framingham Modified Endothelial Function Score
timeFrame: 4 weeks
measure: PedsQL 4.0 - quality of life assessment
timeFrame: 4 weeks
measure: BNP
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: John R Charpie, MD
role: STUDY_DIRECTOR
affiliation: University of Michigan
name: Bryan H Goldstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Cardiol. 2011 Aug 1;108(3):428-34. doi: 10.1016/j.amjcard.2011.03.064. Epub 2011 May 19.
citation: Goldstein BH, Sandelin AM, Golbus JR, Warnke N, Gooding L, King KK, Donohue JE, Yu S, Gurney JG, Goldberg CS, Rocchini AP, Charpie JR. Impact of vitamin C on endothelial function and exercise capacity in patients with a Fontan circulation. Congenit Heart Dis. 2012 May-Jun;7(3):226-34. doi: 10.1111/j.1747-0803.2011.00605.x. Epub 2011 Dec 18.