NETwork of Linoleic Acid Supplementation in Cystic Fibrosis

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 31, 2023

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.

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Linoleic
    • Linoleic acid 13 g and 600 mg algal docosahexaenoic acid (DHA)
  • Active Comparator: Oleic
    • Oleic acid 13 g and 600 algal DHA

Clinical Trial Outcome Measures

Primary Measures

  • Growth
    • Time Frame: 1 year
    • change in BMI, standard deviation score (SDS)
  • Weight
    • Time Frame: 1 year
    • change in SDS body weight
  • Height
    • Time Frame: 1 year
    • change in SDS height

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Try to have similar number of participants of the same sex and age for randomization

Minimum Age: 5 Years

Maximum Age: 15 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Karolinska Institutet
  • Collaborator
    • European Society of Pediatric Gastroenterology, Hepatology and Nutrition
  • Provider of Information About this Clinical Study
    • Principal Investigator: Birgitta Strandvik, MD, PhD, Professor – Karolinska Institutet
  • Overall Official(s)
    • Jaroslaw Walkowiak, MD,PhD, Principal Investigator, University of Poznan, CF center, Poland
    • Carla Colombo, MD,PhD, Principal Investigator, University of Milan, CF center, Italy
    • Egil Bakkeheim, MD, PhD, Principal Investigator, University of Oslo, CF center, Norway
    • Raffaele Badolato, MD, PhD, Principal Investigator, University of Brescia, CF center, Italy
    • Christine Rönne-Hansen, Md, PhD, Principal Investigator, Lund University, CF center, Sweden

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.

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.

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.

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

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