NETwork of Linoleic Acid Supplementation in Cystic Fibrosis

NCT ID: NCT04531410

Last Updated: 2024-11-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-25
• Study Completion Date: 2024-11-05

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Linoleic

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

Group Type: EXPERIMENTAL

linoleic acid supplementation

Intervention Type: DIETARY_SUPPLEMENT

Oils given daily at morning meal with extra enzymes

Oleic

Oleic acid 13 g and 600 algal DHA

Group Type: ACTIVE_COMPARATOR

oleic acid supplementation

Intervention Type: DIETARY_SUPPLEMENT

Oils given at morning meal with extra enzymes

Interventions

linoleic acid supplementation

Oils given daily at morning meal with extra enzymes

Intervention Type: DIETARY_SUPPLEMENT

oleic acid supplementation

Oils given at morning meal with extra enzymes

Intervention Type: DIETARY_SUPPLEMENT

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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Society of Pediatric Gastroenterology, Hepatology and Nutrition

OTHER

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Birgitta Strandvik, MD, PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jaroslaw Walkowiak, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University of Poznan, CF center, Poland

Carla Colombo, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University of Milan, CF center, Italy

Egil Bakkeheim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Oslo, CF center, Norway

Raffaele Badolato, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Brescia, CF center, Italy

Christine Rönne-Hansen, Md, PhD

Role: PRINCIPAL_INVESTIGATOR

Lund University, CF center, Sweden

Locations

Università degli Studi di Milan

Milan, , Italy

Norwegian Resourse Center for Cystic Fibrosis, Oslo University Hospital

Oslo, , Norway

Poznan University of Medical Sciences

Poznan, , Poland

Countries

Italy; Norway; Poland

References

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.

Reference Type: BACKGROUND

PMID: 20673710 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32750662 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33800499 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 35215502 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Ethical approvement

View Document

Document Type: Informed Consent Form: Patients info consent

View Document

Document Type: Informed Consent Form: Patient information Parents

View Document

Other Identifiers

2020-02871

Identifier Type: -

Identifier Source: org_study_id