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

Sponsor

University of Michigan (Other)

Overall Status

Completed

CT.gov ID

NCT00974025

Collaborator

Griese-Hutchinson Champions for Children's Hearts Investigator Award (Other)

Enrollment

Location

Arms

Duration (Months)

5.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fontan Procedure Hypoplastic Left Heart Syndrome Tricuspid Atresia	Dietary Supplement: Vitamin C Dietary Supplement: Placebo	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Mar 1, 2010

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Vitamin C

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

Dietary Supplement: Vitamin C

High-dose Vitamin C will be administered in 4 age-based dosing groups

Placebo Comparator: Placebo

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

Dietary Supplement: Placebo

Placebo will be administered twice daily for four weeks

Outcome Measures

Primary Outcome Measures

Change in peak oxygen consumption (from baseline to post-study drug testing) [4 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

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

Investigators

Study Director: John R Charpie, MD, University of Michigan
Principal Investigator: Bryan H Goldstein, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

John R. Charpie, Professor, University of Michigan

ClinicalTrials.gov Identifier:

NCT00974025

Other Study ID Numbers:

HUM00029464

First Posted:

Sep 10, 2009

Last Update Posted:

Jun 1, 2017

Last Verified:

May 1, 2017

Additional relevant MeSH terms:

Hypoplastic Left Heart Syndrome

Tricuspid Atresia

Ascorbic Acid

Study Results

No Results Posted as of Jun 1, 2017