Choline Nutrition in Children With Cystic Fibrosis (CF)

Study Overview
=================
Brief Summary
-----------------
Cystic Fibrosis (CF) is a complex disease with a wide range of clinical problems. Despite enzyme replacement therapy, children with cystic fibrosis (CF) may still have problems absorbing some nutrients. Detailed studies of the nutrient status of children with CF and have found low amounts of choline, an essential dietary nutrient, and altered levels of some amino acids in almost all patients. Choline is an essential dietary nutrient that is important in many important body functions, which include proving a source of methyl groups, the structure of cell membranes and in acetylcholine. Most choline is present in our diets in a fat known as phosphatidylcholine. Research studies have shown that children with cystic fibrosis do not absorb fat, including phosphatidylcholine very well. In previous studies, we showed that choline provided as a dietary supplement for 2 weeks improved choline status in children with cystic fibrosis. The purpose of this research is to find out if choline supplements over a longer duration of 6 months will improve and maintain normal choline status in children with CF.

Detailed Description
-----------------
This is a prospective study involving 34 children attending an outpatient clinic for children with CF. After enrollment, subjects will be followed for 9 months with each child serving as their own control in a repeated measures design. Chart data, height, weight, pulmonary function, dietary intake and a venous blood and urine sample will be collected at enrollment then every 3 months for 9 months. Choline supplementation will be from enrollment for 6 months, with follow up at 3 months post supplementation. To avoid additional hospital visits and blood draws, and to co-ordinate with pulmonary function, hematology, clinical chemistry tests as part of clinical care, each subject will be seen at routine scheduled clinic appointments, which are every 3 months. The objectives are to determine if supplementation with choline for 6 months corrects biochemical markers of choline deficiency and improves indices of reduced methylation capacity (including methionine, SAM, SAM/SAH) and redox status (GSH/GSSG) based on measures of blood and urine determine whether or not choline supplementation decreases plasma pro-inflammatory mediators determine if choline supplementation improves the low n-6 and n-3 fatty acids levels in children with CF, explore if choline supplementation has the potential to have clinical relevance in reducing recurrent inflammation, and improve pulmonary function and/or reduce liver disease.

Official Title
-----------------
To Investigate Whether Choline Supplementation in Children With CF Will Correct Biochemical Markers of Choline Deficiency and Improve Plasma Indices of Methylation Capacity and Redox Status and Result in Decreased Pro-inflammatory Cytokines

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: Choline supplementation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children with Cystic Fibrosis of known genotype. Exclusion Criteria: No hospitalizations within the previous month not receiving parenteral nutrition FEV1 > 50% at enrollment BMI and weight for age z-scores > 5th percentile non smokers no asthma not taking any lipid supplement or other agent designed to effect glutathione status.

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Choline supplementation|Chart data, height, weight, pulmonary function, dietary intake and a venous blood and urine sample will be collected at enrollment then every 3 months for 9 months. Choline supplementation will be from enrollment for 6 months, with follow up at 3 months post supplementation. To avoid additional hospital visits and blood draws, and to co-ordinate with pulmonary function, hematology, clinical chemistry tests as part of clinical care, each subject will be seen at routine scheduled clinic appointments, which are every 3 months.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measured at: 0 (baseline), 3 and 6 mth (6 mth supplementation) and 9 mths (3 mth post supplementation) a) choline and methyl metabolites b) redox status (GSH/GSSG) |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measured at: 0, 3 and 6 mth and 9 mth a) inflammatory markers (IL-8, IL-6. IL-1ß, TNFα) b) essential n-6 and n-3 fatty acids c) pulmonary function (FVC, FEV1 (FEF 25-75) d) liver function (serum liver enzymes) |  | 9 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cystic Fibrosis, choline nutrition, choline and methyl metabolism, CF and oxidative stress