Back to resultsCod Liver Oil for Covid-19 Prevention Study
Primary Purpose
Covid-19, Respiratory Tract Infections
Status
Completed
Phase
Phase 4
Locations
Norway
Study Type
Interventional
Intervention
Cod liver oil
Corn oil (placebo)
Sponsored by
About this trial
This is an interventional prevention trial for Covid-19 focused on measuring Cod liver oil, Vitamin D, n-3 LCPUFAs, SARS-CoV virus
Eligibility Criteria
Inclusion Criteria:
- Any person >18 years with a Norwegian Personal Identity Number
Exclusion Criteria:
- History of renal failure or dialysis, hypercalcemia, severe liver disease (cirrhosis), sarcoidosis or other granulomatous diseases (Wegener)
- Allergy to fish or corn oil.
- Pregnancy or planned pregnancy before summer 2021
- Vegan diet
- Age >75 years old at inclusion based on the Norwegian Personal Identity Number
- Difficulty in swallowing cod liver oil or other oils
- Previous Covid-19 disease
- For Caucasians only: Use of any supplement containing more than trace amounts of vitamin D or omega-3 fatty acids at inclusion (Vitamin D levels in non-Caucasians living in Norway are frequently low even among those self-reporting using dietary supplements). This criterion will be relaxed if too few participants volunteer for the study and only Caucasians that use cod liver oil or an equivalent dietary supplement (with omega 3 and vitamin D) more than 5-7 times per week will be excluded.
Sites / Locations
- Oslo University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Cod liver oil
Corn oil (placebo)
Arm Description
supplementation for 6 months
supplementation for 6 months
Outcomes
Primary Outcome Measures
Number of participants diagnosed with serious Covid-19
The number of participants with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories in the period from one week after the start of cod liver oil/placebo taking to the end of this period together with any of the following:
A) Self-reported dyspnea and fever concurrent (within four weeks) with the positive test OR B) hospitalization caused by Covid-19 concurrent (within four weeks) with the positive test OR C) death where the Covid-19 infection was wholly or partly responsible as judged by the death certificate (see endpoint in the protocol)
Number of participants diagnosed with New Covid-19
The number of participants diagnosed with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories from one week after the start of cod liver oil/placebo taking.
Number of participants with negative SARS-CoV-2 test
Number of participants with an airway sample negative for SARS-CoV-2 (indicative of another airway infection).
*Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories.
Number of participants with self-reported airway infection
The number of episodes with any two of the following symptoms: fever, cough, nasal congestion or sore throat
Secondary Outcome Measures
Number of participants hospitalized due to Covid-19
Number of participants hospitalized wholly or partly caused by Covid-19.
Number of participants in Intensiv Care Unit (ICU) caused by Covid-19
Number of participants with ICU care wholly or partly caused by Covid-19.
Number of participants with any admissions to hospital
Number of participants with any admissions to hospital based on the Norwegian Patient Registry data.
Infection with each of the mentioned pathogens
An airway sample positive for a respiratory pathogen* (either PCR or culture) in the period from one week after the start of cod liver oil/placebo taking to the end of this period.
*Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories.
Number of visits at GP for infections
Based on The Norwegian Reimbursement Database
Number of visits at GP
Based on The Norwegian Reimbursement Database
Full Information
NCT ID
NCT04609423
First Posted
October 22, 2020
Last Updated
March 28, 2022
Sponsor
Oslo University Hospital
Collaborators
University of Oslo, Norwegian Institute of Public Health
1. Study Identification
Unique Protocol Identification Number
NCT04609423
Brief Title
Cod Liver Oil for Covid-19 Prevention Study
Official Title
A Randomized, Parallel-group Treatment, Quadruple Masked, Two-arm Study, to Assess the Effectiveness of Cod Liver Oil Compared to Placebo in the Prevention of Covid-19 and Airway Infections in Healthy Adults
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
November 10, 2020 (Actual)
Primary Completion Date
June 2, 2021 (Actual)
Study Completion Date
June 2, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
Collaborators
University of Oslo, Norwegian Institute of Public Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
A randomized, parallel-group treatment, quadruple masked, two-arm study to assess the effectiveness of cod liver oil compared to placebo in the prevention of Covid-19 and airway infections in healthy adults.
In this study, the investigators will investigate whether daily cod liver oil can prevent Covid-19 infections and reduce the severity of such infections. The investigators will also examine whether cod liver oil prevents other airway infections in healthy adults.
Detailed Description
Preliminary evidence from literature and an ongoing study in the investigators' lab suggests that cod liver oil may prevent Covid-19 and complications of Covid-19. In the present study, the investigators will examine whether this is actually the case by randomizing volunteers to take cod liver oil or placebo (corn oil) during the winter months of 2020-2021. The investigators also aim to explore whether cod liver oil can prevent other respiratory tract infections, as well as explore and confirm already known health effects and possible new health effects, in particular rare adverse events associated with cod liver oil use.
Cod liver oil is a traditional source of vitamin A, D, and E and omega-3 fatty acids and the dose administered in the study will contain 250 ug vitamin A, 10 ug vitamin D, 10 mg vitamin E, and 1,2 g omega-3 fatty acids.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid-19, Respiratory Tract Infections
Keywords
Cod liver oil, Vitamin D, n-3 LCPUFAs, SARS-CoV virus
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A parallel-group treatment, two-arm study where participants are randomly assigned to cod liver oil or placebo (corn oil) in a 1:1 ratio
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants, investigators, care providers, data collectors, outcomes assessors, and data analysts will be masked to the group assignment of each participant.
Unmasking will be done after analysis of all primary endpoints and, preferably, also all secondary endpoints are completed.
After unmasking the unmasked list will only be made available to study personnel needing this for conducting their tasks.
Allocation
Randomized
Enrollment
47210 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cod liver oil
Arm Type
Experimental
Arm Description
supplementation for 6 months
Arm Title
Corn oil (placebo)
Arm Type
Placebo Comparator
Arm Description
supplementation for 6 months
Intervention Type
Dietary Supplement
Intervention Name(s)
Cod liver oil
Other Intervention Name(s)
10 ug of vitamin D and 1 g n-3 LCPUFA, Tran
Intervention Description
5 ml of cod liver oil as a source of 10 ug of vitamin D and 1.2 g of long-chained n-3 polyunsaturated fatty acids (DHA 0,6g and EPA 0,4g) per day for 6 months x 1 time/day together with the first meal of the day. 5ml of Cod liver oil also contains 250ug vitamin A and 10 mg vitamin E.
Intervention Type
Dietary Supplement
Intervention Name(s)
Corn oil (placebo)
Intervention Description
5 ml of corn oil per day for 6 months x 1 time/day together with the first meal of the day
Primary Outcome Measure Information:
Title
Number of participants diagnosed with serious Covid-19
Description
The number of participants with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories in the period from one week after the start of cod liver oil/placebo taking to the end of this period together with any of the following:
A) Self-reported dyspnea and fever concurrent (within four weeks) with the positive test OR B) hospitalization caused by Covid-19 concurrent (within four weeks) with the positive test OR C) death where the Covid-19 infection was wholly or partly responsible as judged by the death certificate (see endpoint in the protocol)
Time Frame
6 months
Title
Number of participants diagnosed with New Covid-19
Description
The number of participants diagnosed with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories from one week after the start of cod liver oil/placebo taking.
Time Frame
6 months
Title
Number of participants with negative SARS-CoV-2 test
Description
Number of participants with an airway sample negative for SARS-CoV-2 (indicative of another airway infection).
*Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories.
Time Frame
6 months
Title
Number of participants with self-reported airway infection
Description
The number of episodes with any two of the following symptoms: fever, cough, nasal congestion or sore throat
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Number of participants hospitalized due to Covid-19
Description
Number of participants hospitalized wholly or partly caused by Covid-19.
Time Frame
6 months
Title
Number of participants in Intensiv Care Unit (ICU) caused by Covid-19
Description
Number of participants with ICU care wholly or partly caused by Covid-19.
Time Frame
6 months
Title
Number of participants with any admissions to hospital
Description
Number of participants with any admissions to hospital based on the Norwegian Patient Registry data.
Time Frame
6 months
Title
Infection with each of the mentioned pathogens
Description
An airway sample positive for a respiratory pathogen* (either PCR or culture) in the period from one week after the start of cod liver oil/placebo taking to the end of this period.
*Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories.
Time Frame
6 months
Title
Number of visits at GP for infections
Description
Based on The Norwegian Reimbursement Database
Time Frame
6 months
Title
Number of visits at GP
Description
Based on The Norwegian Reimbursement Database
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Incidence of Cardiovascular disease
Description
Based on self-reporting and Norwegian Registries
Time Frame
6 months
Title
Incidence of Cardiovascular disease
Description
Based on self-reporting and Norwegian Registries
Time Frame
30 months
Title
Incidence of cardiovascular mortality
Description
Based on self-reporting and Norwegian Registries
Time Frame
6 months
Title
Incidence of cardiovascular mortality
Description
Based on self-reporting and Norwegian Registries
Time Frame
30 months
Title
Incidence of cancer
Description
Based on self-reporting and Norwegian Registries
Time Frame
6 months
Title
Incidence of cancer
Description
Based on self-reporting and Norwegian Registries
Time Frame
30 months
Title
Incidence of cancer mortality
Description
Based on self-reporting and Norwegian Registries
Time Frame
6 months
Title
Incidence of cancer mortality
Description
Based on self-reporting and Norwegian Registries
Time Frame
30 months
Title
All-cause mortality
Description
Based on self-reporting and Norwegian Registries
Time Frame
6 months
Title
All-cause mortality
Description
Based on self-reporting and Norwegian Registries
Time Frame
30 months
Title
Incidence of fracture of the hip or forearm
Description
Based on self-reporting and Norwegian Registries
Time Frame
6 months
Title
Incidence of fracture of the hip or forearm
Description
Based on self-reporting and Norwegian Registries
Time Frame
30 months
Title
Incident dementia
Description
Based on self-reporting and Norwegian Registries
Time Frame
6 months
Title
Incident dementia
Description
Based on self-reporting and Norwegian Registries
Time Frame
30 months
Title
Number of participants diagnosed with serious Covid-19
Description
The number of participants with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories in the period from one week after the start of cod liver oil/placebo taking to the end of this period together with any of the following:
A) Self-reported dyspnea and fever concurrent (within four weeks) with the positive test OR B) hospitalization caused by Covid-19 concurrent (within four weeks) with the positive test OR C) death where the Covid-19 infection was wholly or partly responsible as judged by the death certificate (see endpoint in the protocol)
Time Frame
12 months
Title
Number of participants diagnosed with new Covid-19
Description
The number of participants diagnosed with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories from one week after the start of cod liver oil/placebo taking.
Time Frame
12 months
Title
Laboratory confirmed respiratory tract infection
Description
An airway sample positive for a respiratory pathogen* (either PCR or culture).
*Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories.
Time Frame
12 months
Title
Self-reported airway infection
Description
The number of episodes with any two of the following symptoms: fever, cough, nasal congestion or sore throat
Time Frame
12 months
Title
Number of participants with self-reported cod liver oil related adverse events
Description
Number of participants with self-reported adverse events
Time Frame
12 months
Title
Number of participants with cod liver oil related adverse events
Description
Number of participants hospitalized for major diseases or death in the cod liver oil versus placebo group in Norwegian registries
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Any person >18 years with a Norwegian Personal Identity Number
Exclusion Criteria:
History of renal failure or dialysis, hypercalcemia, severe liver disease (cirrhosis), sarcoidosis or other granulomatous diseases (Wegener)
Allergy to fish or corn oil.
Pregnancy or planned pregnancy before summer 2021
Vegan diet
Age >75 years old at inclusion based on the Norwegian Personal Identity Number
Difficulty in swallowing cod liver oil or other oils
Previous Covid-19 disease
For Caucasians only: Use of any supplement containing more than trace amounts of vitamin D or omega-3 fatty acids at inclusion (Vitamin D levels in non-Caucasians living in Norway are frequently low even among those self-reporting using dietary supplements). This criterion will be relaxed if too few participants volunteer for the study and only Caucasians that use cod liver oil or an equivalent dietary supplement (with omega 3 and vitamin D) more than 5-7 times per week will be excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arne Søraas, MD, PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
0424
Country
Norway
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
IPD is complicated to share under the European General Data Protection Regulative, however, it is an aim of the study to make such data available within these regulations.
Citations:
PubMed Identifier
36215222
Citation
Brunvoll SH, Nygaard AB, Ellingjord-Dale M, Holland P, Istre MS, Kalleberg KT, Soraas CL, Holven KB, Ulven SM, Hjartaker A, Haider T, Lund-Johansen F, Dahl JA, Meyer HE, Soraas A. Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial. BMJ. 2022 Sep 7;378:e071245. doi: 10.1136/bmj-2022-071245.
Results Reference
derived
Learn more about this trial
Cod Liver Oil for Covid-19 Prevention Study
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