NETwork of Linoleic Acid Supplementation in Cystic Fibrosis

Study Overview
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Brief Summary
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Undernutrition is a common problem in patients with cystic fibrosis (CF) despite international consensus that the patients shall be given 120-200% of energy recommendations. Studies imply that one problem might be that the patients are not compensated for the essential fatty acid deficiency (linoleic acid, LA), which is well known in these patients. This deficiency is shown not to be due to fat malabsorption, but related to an increased turnover of arachidonic acid, a transformation product of LA. This abnormality is related to mutations associated with a more severe clinical phenotype. The most common and typical symptom of LA deficiency is poor growth. Studies in animals have further indicated that many of the symptoms in CF are related to the deficiency. A series of recent prospective studies from Wisconsin corroborate the importance of LA for growth. In Sweden LA has been supplemented to most patients since the late 70´, and the condition of patients have been among the leading in the world regarding growth, pulmonary function and survival. Short-term studies have shown better effect of LA supplementation compared to similar supply of energy without including extra LA. There are few long-term studies, performed before the gene was identified, giving very heterogeneous patient groups in regard to genotype, but with some positive results on growth and physiology. It´s of interest that modern personalized extremely expensive therapy with correctors and potentiators for Cystic Fibrosis Transmembrane Conductance Regulator may influence lipid metabolism. LA might thus tentatively be a cheap adjuvant to this modern therapy, but this has to be specially studied. The aim of the study is to find if there are differences in clinical and metabolic outcome between two groups, blindly given similar amount of extra calories, in one group consisting of linoleic acid.The benefit for the patients would be great if the expected positive effect can be proved in the planned study. The treatment will be cheap and without adverse effects. From socioeconomic point of view is would be a great advantage.

Detailed Description
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Two group of matched children with CF were randomized to two type of oils given 20 g oil and 600 mg DHA daily for one year and anthropometry, pulmonary function, biochemistry, resting energy expenditure, lipid mediators, inflammatory and intestinal markers were studied at start and at 6 months and 1 year. Dietary intake was controlled and life quality recording at start and end of study.

Official Title
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Double-blind Randomized Controlled Study of Linoleic Acid Supplementation for 1 Year in Patients With Cystic Fibrosis - Influence on Clinical Status and Metabolism

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Dietary Supplement: linoleic acid supplementation
* Dietary Supplement: oleic acid supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Two mutations related to severe clinical status such as dF508, or other stop mutations or class II mutations. Severe status includes pancreatic insufficiency Exclusion Criteria: Liver cirrhosis and/or portal hypertension, transplantation or on transplantation list, intake of lipid supplements the latest 2 months

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel, double blind, randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linoleic<br>Linoleic acid 13 g and 600 mg algal docosahexaenoic acid (DHA) | Dietary Supplement: linoleic acid supplementation<br>* Oils given daily at morning meal with extra enzymes<br>|
| Active Comparator: Oleic<br>Oleic acid 13 g and 600 algal DHA | Dietary Supplement: oleic acid supplementation<br>* Oils given at morning meal with extra enzymes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth | change in BMI, standard deviation score (SDS) | 1 year | 
| Weight | change in SDS body weight | 1 year | 
| Height | change in SDS height | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function | change in forced expiratory volume in one second (FEV1 % of predicted) | 1 year | 
| Quality of life, the patient experience of well being | Questionaire about health, physical activity, well being (8 items), CFQ-child + CFQ- parents (higher rates are better) The score changes are analysed.The CFQ considers the physical, image, digestive, respiratory, emotional, social, food, treatment, vitality, health, social role and weight domains. Each domain has a score and its sum generates the total score, whose values can vary from 0 to 100 The scores will also be related to measurements. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arachidonic acid,, lipid mediators, cytokines, growth, pulmonary function, IGF-1, resting energy expenditure, docosahexaenoic acid