Clinical trial NCT04531410: NETwork of Linoleic Acid Supplementation in Cystic Fibrosis
Official title: Double-blind Randomized Controlled Study of Linoleic Acid Supplementation for 1 Year in Patients With Cystic Fibrosis - Influence on Clinical Status and Metabolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Keywords: arachidonic acid,
lipid mediators
cytokines
growth
pulmonary function
IGF-1
resting energy expenditure
docosahexaenoic acid
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: European Society of Pediatric Gastroenterology, Hepatology and Nutrition
First posted: 2020-08-28
Enrollment: 50
Sex: ALL
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel, double blind, randomized
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Growth
timeFrame: 1 year
measure: Weight
timeFrame: 1 year
measure: Height
timeFrame: 1 year
Secondary outcomes:
measure: Pulmonary function
timeFrame: 1 year
measure: Quality of life, the patient experience of well being
timeFrame: 1 year
Other outcomes:
measure: Lipid mediators
timeFrame: 1 year
measure: Clinical infectious status
timeFrame: 1 year
measure: Influence on sodium status
timeFrame: 1 year
measure: Inflammatory markers
timeFrame: 1 year
measure: Metabolic marker
timeFrame: 1 year
measure: Energy metabolism
timeFrame: 1 year
measure: Bone mineral density
timeFrame: 1 year
measure: Oral glucose tolerance
timeFrame: 1 year
Locations:
city: Milan
country: Italy
facility: Università degli Studi di Milan
city: Oslo
country: Norway
facility: Norwegian Resourse Center for Cystic Fibrosis, Oslo University Hospital
city: Poznań
country: Poland
facility: Poznan University of Medical Sciences
Study officials:
affiliation: University of Poznan, CF center, Poland
name: Jaroslaw Walkowiak, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Milan, CF center, Italy
name: Carla Colombo, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oslo, CF center, Norway
name: Egil Bakkeheim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Brescia, CF center, Italy
name: Raffaele Badolato, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lund University, CF center, Sweden
name: Christine Rönne-Hansen, Md, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Strandvik B. Fatty acid metabolism in cystic fibrosis. Prostaglandins Leukot Essent Fatty Acids. 2010 Sep;83(3):121-9. doi: 10.1016/j.plefa.2010.07.002. Epub 2010 Jul 31.
citation: Wheelock CE, Strandvik B. Abnormal n-6 fatty acid metabolism in cystic fibrosis contributes to pulmonary symptoms. Prostaglandins Leukot Essent Fatty Acids. 2020 Sep;160:102156. doi: 10.1016/j.plefa.2020.102156. Epub 2020 Jun 26.
citation: Strandvik B. Is the ENaC Dysregulation in CF an Effect of Protein-Lipid Interaction in the Membranes? Int J Mol Sci. 2021 Mar 8;22(5):2739. doi: 10.3390/ijms22052739.
citation: Strandvik B. Nutrition in Cystic Fibrosis-Some Notes on the Fat Recommendations. Nutrients. 2022 Feb 18;14(4):853. doi: 10.3390/nu14040853.