NETLACF: NETwork of Linoleic Acid Supplementation in Cystic Fibrosis

Sponsor

Karolinska Institutet (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04531410

Collaborator

European Society of Pediatric Gastroenterology, Hepatology and Nutrition (Other)

Enrollment

Locations

Arms

27.2

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Dietary Supplement: linoleic acid supplementation Dietary Supplement: oleic acid supplementation	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel, double blind, randomizedParallel, double blind, randomized

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The supplement only differ by colour on capsulae, no labelling

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 25, 2021

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Jan 31, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Linoleic

Linoleic acid 13 g and 600 mg algal docosahexaenoic acid (DHA)

Dietary Supplement: linoleic acid supplementation

Oils given daily at morning meal with extra enzymes

Active Comparator: Oleic

Oleic acid 13 g and 600 algal DHA

Dietary Supplement: oleic acid supplementation

Oils given at morning meal with extra enzymes

Outcome Measures

Primary Outcome Measures

Growth [1 year]
change in BMI, standard deviation score (SDS)
Weight [1 year]
change in SDS body weight
Height [1 year]
change in SDS height

Secondary Outcome Measures

Pulmonary function [1 year]
change in forced expiratory volume in one second (FEV1 % of predicted)
Quality of life, the patient experience of well being [1 year]
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.

Other Outcome Measures

Lipid mediators [1 year]
change in lipid mediators in blood and urine, ion trap- Mass Spectrometry, picoMol (> 150 products of both the n-6 and n-3 series)
Clinical infectious status [1 year]
change in number exacerbations compare to previous year,
Influence on sodium status [1 year]
change in Sodium in sweat test, mol/L and urine (fractional sodium excretion)
Inflammatory markers [1 year]
change in Cytokines, Proximity extension assays (PEA proteomics) picogram/ml
Metabolic marker [1 year]
Change in serum insulin growth factor -1 (IGF-1, nanogram/ml)
Energy metabolism [1 year]
Change in resting energy expenditure (REE/kg body weight)
Bone mineral density [1 year]
Change in total bone mineral density by dual x-ray absorptiometry (DXA), gram/cm^2
Oral glucose tolerance [1 year]
Measure of glucose and insuline after oral glucose loading

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 15 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centro Regionale di Supporto per la Fibrosei Cistica, ASST Spedali civili, Univ of Brescia	Brescia	Brescia - Lombardia	Italy	25123
2	Università degli Studi di Milan	Milan		Italy
3	Norwegian Resourse Center for Cystic Fibrosis, Oslo University Hospital	Oslo		Norway
4	Poznan University of Medical Sciences	Poznań		Poland
5	Center of Cystic fibrosis, Dept of Pediatrics, Lund University Hospital	Lund	Skåne	Sweden	22242

Sponsors and Collaborators

Karolinska Institutet
European Society of Pediatric Gastroenterology, Hepatology and Nutrition

Investigators

Principal Investigator: Jaroslaw Walkowiak, MD,PhD, University of Poznan, CF center, Poland
Principal Investigator: Carla Colombo, MD,PhD, University of Milan, CF center, Italy
Principal Investigator: Egil Bakkeheim, MD, PhD, University of Oslo, CF center, Norway
Principal Investigator: Raffaele Badolato, MD, PhD, University of Brescia, CF center, Italy
Principal Investigator: Christine Rönne-Hansen, Md, PhD, Lund University, CF center, Sweden