NETwork of Linoleic Acid Supplementation in Cystic Fibrosis

NCT04531410 | Completed DMC

• 1 other identifier: 2020-02871
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 3

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.

Conditions

Cystic Fibrosis

Keywords

arachidonic acid,; lipid mediators; cytokines; growth; pulmonary function; IGF-1; resting energy expenditure; docosahexaenoic acid

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Pulmonary function

  1 year

• Quality of life, the patient experience of well being

  1 year

Other Outcomes (8)

• Lipid mediators

  1 year

• Clinical infectious status

  1 year

• Influence on sodium status

  1 year

Study Arms (2)

Linoleic

EXPERIMENTAL

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

Dietary Supplement: linoleic acid supplementation

Oleic

ACTIVE COMPARATOR

Oleic acid 13 g and 600 algal DHA

Dietary Supplement: oleic acid supplementation

Interventions

linoleic acid supplementation DIETARY_SUPPLEMENT

Oils given daily at morning meal with extra enzymes

Linoleic

oleic acid supplementation DIETARY_SUPPLEMENT

Oils given at morning meal with extra enzymes

Oleic

Eligibility Criteria

• Age: 5 Years - 15 Years
• Gender Eligibility Details: Try to have similar number of participants of the same sex and age for randomization
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Two mutations related to severe clinical status such as dF508, or other stop mutations or class II mutations. Severe status includes pancreatic insufficiency

You may not qualify if:

• Liver cirrhosis and/or portal hypertension, transplantation or on transplantation list, intake of lipid supplements the latest 2 months

Sponsors & Collaborators

• Karolinska Institutet: lead
• European Society of Pediatric Gastroenterology, Hepatology and Nutrition: collaborator

Study Sites (3)

Università degli Studi di Milan

Milan, Italy

Location

Norwegian Resourse Center for Cystic Fibrosis, Oslo University Hospital

Oslo, Norway

Location

Poznan University of Medical Sciences

Poznan, Poland

Location

Related 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.

  PMID: 20673710 BACKGROUND

• 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.

  PMID: 32750662 BACKGROUND

• 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.

  PMID: 33800499 BACKGROUND

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

  PMID: 35215502 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The supplement only differ by colour on capsulae, no labelling
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Parallel, double blind, randomized

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: August 28, 2020
• Study Start: October 25, 2021
• Primary Completion: October 31, 2024
• Study Completion: November 5, 2024
• Last Updated: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); IT (1); PL (1)