NETwork of Linoleic Acid Supplementation in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— NETLACF  

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04531410
• Other study ID #: 2020-02871
• Status: Enrolling by invitation
• Phase: N/A
• Start date: October 25, 2021
• Est. completion date: January 31, 2024

Study information

• Verified date: March 2022
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: January 31, 2024
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Dietary Supplement:
• linoleic acid supplementation
Oils given daily at morning meal with extra enzymes
• oleic acid supplementation
Oils given at morning meal with extra enzymes

Locations

Country	Name	City	State
Italy	Centro Regionale di Supporto per la Fibrosei Cistica, ASST Spedali civili, Univ of Brescia	Brescia	Brescia - Lombardia
Italy	Università degli Studi di Milan	Milan
Norway	Norwegian Resourse Center for Cystic Fibrosis, Oslo University Hospital	Oslo
Poland	Poznan University of Medical Sciences	Poznan
Sweden	Center of Cystic fibrosis, Dept of Pediatrics, Lund University Hospital	Lund	Skåne

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska Institutet	European Society of Pediatric Gastroenterology, Hepatology and Nutrition

Countries where clinical trial is conducted

Italy,  Norway,  Poland,  Sweden, 

References & Publications (4)

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. Review. — View 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). pii: 2739. doi: 10.3390/ijms22052739. Review. — View Citation

Strandvik B. Nutrition in Cystic Fibrosis-Some Notes on the Fat Recommendations. Nutrients. 2022 Feb 18;14(4). pii: 853. doi: 10.3390/nu14040853. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Lipid mediators	change in lipid mediators in blood and urine, ion trap- Mass Spectrometry, picoMol (> 150 products of both the n-6 and n-3 series)	1 year
Other	Clinical infectious status	change in number exacerbations compare to previous year,	1 year
Other	Influence on sodium status	change in Sodium in sweat test, mol/L and urine (fractional sodium excretion)	1 year
Other	Inflammatory markers	change in Cytokines, Proximity extension assays (PEA proteomics) picogram/ml	1 year
Other	Metabolic marker	Change in serum insulin growth factor -1 (IGF-1, nanogram/ml)	1 year
Other	Energy metabolism	Change in resting energy expenditure (REE/kg body weight)	1 year
Other	Bone mineral density	Change in total bone mineral density by dual x-ray absorptiometry (DXA), gram/cm^2	1 year
Other	Oral glucose tolerance	Measure of glucose and insuline after oral glucose loading	1 year
Primary	Growth	change in BMI, standard deviation score (SDS)	1 year
Primary	Weight	change in SDS body weight	1 year
Primary	Height	change in SDS height	1 year
Secondary	Pulmonary function	change in forced expiratory volume in one second (FEV1 % of predicted)	1 year
Secondary	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