Cystic FibrosisNETLACFNCT04531410
NETwork of Linoleic Acid Supplementation in Cystic Fibrosis
A study testing linoleic acid supplementation and oleic acid supplementation in people with Cystic Fibrosis, run by Karolinska Institutet at 3 sites in 3 countries.
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… Read more about this study
- Who is it for?
- Ages 5 to 15 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- linoleic acid supplementation and oleic acid supplementation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 25 Oct 2021to 5 Nov 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Two mutations related to severe clinical status such as dF508, or other stop mutations or class II mutations. Severe status includes pancreatic insufficiency
Who cannot join
- Liver cirrhosis and/or portal hypertension, transplantation or on transplantation list, intake of lipid supplements the latest 2 months
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Norway1 site
Norwegian Resourse Center for Cystic Fibrosis, Oslo University Hospital
Oslo
About this study
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
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.
Read the 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
- Being tested
- linoleic acid supplementation, oleic acid supplementation
- Keywords
- arachidonic acid,, lipid mediators, cytokines, growth, pulmonary function, IGF-1, resting energy expenditure, docosahexaenoic acid
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
linoleic acid supplementationDietary supplement
Oils given daily at morning meal with extra enzymes
oleic acid supplementationDietary supplement
Oils given at morning meal with extra enzymes
| Study group | Role | What they receive |
|---|---|---|
| Linoleic | Experimental | Linoleic acid 13 g and 600 mg algal docosahexaenoic acid (DHA) Receives: Dietary Supplement: linoleic acid supplementation |
| Oleic | Active comparator | Oleic acid 13 g and 600 algal DHA Receives: Dietary Supplement: oleic acid supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Growth
change in BMI, standard deviation score (SDS)
Measured: 1 year
Weight
change in SDS body weight
Measured: 1 year
Height
change in SDS height
Measured: 1 year
Secondary outcomes (2)
Pulmonary function
change in forced expiratory volume in one second (FEV1 % of predicted)
Measured: 1 year
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2020
- Study start25 Oct 2021
- Primary completion31 Oct 2024
- Study completion5 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel, double blind, randomized
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- European Society of Pediatric Gastroenterology, Hepatology and Nutrition
- Responsible party
- Principal investigator, Birgitta Strandvik, MD, PhD, Karolinska Institutet
- Investigators
- Jaroslaw Walkowiak, MD,PhD, Principal investigator, University of Poznan, CF center, PolandCarla Colombo, MD,PhD, Principal investigator, University of Milan, CF center, ItalyEgil Bakkeheim, MD, PhD, Principal investigator, University of Oslo, CF center, NorwayRaffaele Badolato, MD, PhD, Principal investigator, University of Brescia, CF center, ItalyChristine Rönne-Hansen, Md, PhD, Principal investigator, Lund University, CF center, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04531410
- Sponsor's protocol ID
- 2020-02871
- Acronym
- NETLACF
- Status last verified
- Nov 2024
- First submitted
- 18 Aug 2020
- Last updated
- 26 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The results will be anonymous and reported to peer review journals for publication. Beside the local PIs there will be other local staff involved and for the analyses also co-workers as shown in the study protocol which will be attached for review.
Publications
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.
PubMed 20673710Wheelock 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.
PubMed 32750662Strandvik 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.
PubMed 33800499Strandvik B. Nutrition in Cystic Fibrosis-Some Notes on the Fat Recommendations. Nutrients. 2022 Feb 18;14(4):853. doi: 10.3390/nu14040853.
PubMed 35215502
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04531410
- Acronym / sponsor ID
- NETLACF / 2020-02871
- Conditions
- Cystic Fibrosis
- Keywords
- arachidonic acid,, lipid mediators, cytokines, growth, pulmonary function, IGF-1, resting energy expenditure, docosahexaenoic acid
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- European Society of Pediatric Gastroenterology, Hepatology and Nutrition
- Study start
- 25 Oct 2021 (actual)
- Primary completion
- 31 Oct 2024 (actual)
- Study completion
- 5 Nov 2024 (actual)
- First posted
- 28 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel, double blind, randomized
| Arm | Type | Receives |
|---|---|---|
| Linoleic | Experimental | Dietary Supplement: linoleic acid supplementationLinoleic acid 13 g and 600 mg algal docosahexaenoic acid (DHA) |
| Oleic | Active comparator | Dietary Supplement: oleic acid supplementationOleic acid 13 g and 600 algal DHA |
Who may qualify
- Ages
- 5 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Two mutations related to severe clinical status such as dF508, or other stop mutations or class II mutations. Severe status includes pancreatic insufficiency
Key exclusion criteria (1 listed)
- Liver cirrhosis and/or portal hypertension, transplantation or on transplantation list, intake of lipid supplements the latest 2 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| linoleic acid supplementationOils given daily at morning meal with extra enzymes | Dietary supplement | Linoleic |
| oleic acid supplementationOils given at morning meal with extra enzymes | Dietary supplement | Oleic |
Primary outcome
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
2 secondary outcomes
Pulmonary function
Time frame: 1 year
Quality of life, the patient experience of well being
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2024.
- Background: PubMed 20673710Strandvik 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.
- Background: PubMed 32750662Wheelock 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.
- Background: PubMed 33800499Strandvik 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.
- Background: PubMed 35215502Strandvik B. Nutrition in Cystic Fibrosis-Some Notes on the Fat Recommendations. Nutrients. 2022 Feb 18;14(4):853. doi: 10.3390/nu14040853.
- Individual participant dataSharing planned: No. The results will be anonymous and reported to peer review journals for publication. Beside the local PIs there will be other local staff involved and for the analyses also co-workers as shown in the study protocol which will be attached for review.
Related trials for Cystic Fibrosis
RecruitingPhase 2
A Study of 24 to 52 Weeks Treatment to Evaluate The Efficacy And Safety of Galvokimig in Adult Study Participants With Non-Cystic Fibrosis Bronchiectasis
Non-cystic Fibrosis Bronchiectasis
Active, not recruitingObservational study
CFTR Modulator Effects on Bone and Muscle in Adults With Cystic Fibrosis
Cystic Fibrosis, Bone Loss
RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
RecruitingPhase 2
Early Study on Tamoxifen Safety/Tolerability in Cystic Fibrosis Patients Unable to Use CFTR Modulators.
Cystic Fibrosis - Complete
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing linoleic acid supplementation and oleic acid supplementation in people with Cystic Fibrosis, run by Karolinska Institutet at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy, Norway, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Growth (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04531410, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.