Choline Nutrition in Children With Cystic Fibrosis (CF)
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.
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
1. 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
2. determine whether or not choline supplementation decreases plasma pro-inflammatory mediators
3. determine if choline supplementation improves the low n-6 and n-3 fatty acids levels in children with CF,
4. explore if choline supplementation has the potential to have clinical relevance in reducing recurrent inflammation, and improve pulmonary function and/or reduce liver disease.
Study Design
Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Conditions
Cystic Fibrosis
Intervention
Choline supplementation
Location
Nutrition Research Program, BC Children's Hospital
Vancouver
British Columbia
Canada
V6H 3V4
Status
Recruiting
Source
University of British Columbia
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00686361
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Cystic Fibrosis
An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.
Cystic Fibrosis Transmembrane Conductance Regulator
A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)
Mice, Inbred Cftr
A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.
Cytidine Diphosphate Choline
Donor of choline in biosynthesis of choline-containing phosphoglycerides.
Choline Kinase
An enzyme that is active in the first step of choline phosphoglyceride (lecithin) biosynthesis by catalyzing the phosphorylation of choline to phosphorylcholine in the presence of ATP. Ethanolamine and its methyl and ethyl derivatives can also act as acceptors. EC 2.7.1.32.
Clinical Trials
Choline Nutritional Status Of Children With Cystic Fibrosis X-Sectional Study
Cystic fibrosis (CF) is the most common lethal, inherited disorder among Caucasians. Choline is an essential vitamin and as a methyl donor is critically needed to support the normal metabo...
Choline Nutrition in Children With Cystic Fibrosis
Cystic fibrosis (CF) is the most common lethal, inherited disorder among Caucasians. Choline is an essential vitamin and as a methyl donor is critically needed to support the normal metabo...
Study of LYM-X-SORB™ to Improve Fatty Acid and Choline Status in Children With CF and PI
The purpose of this phase II research study is to evaluate the effectiveness of the next generation LYM-X-SORB™ in improving the essential fatty acid (EFA) and choline status for childre...
Oral Docosahexanoic Acid Supplementation in Cystic Fibrosis
Oral supplementation of patients affected by cystic fibrosis with docosahexanoic acid (DHA) will result in normalization of the known fatty acid derangements in these patients and will dim...
Miglustat / OGT 918 in the Treatment of Cystic Fibrosis
Cystic fibrosis is a genetic disease caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR). The purpose of the study is to investigate the effects of miglust...
PubMed Articles
New therapies in cystic fibrosis.
Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to abnormalities in transepithelial ion transport in the airways of affected pat...
A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.
Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis.
Treatment of cystic fibrosis associated cutaneous vasculitis with chloroquine.
Vasculitis is a well recognised complication of Cystic Fibrosis. Corticosteroids are the mainstay of treatment but some cases can be resistant and may require additional disease modifying agents. We d...
We studied the long-term effects of a postnatal choline supplementation (from birth till weaning) in the truncated MeCP2-308 mouse model of Rett syndrome. Adult male mutant hemizygous (hz) mice showed...
