Cod Liver Oil for Covid-19 Prevention Study

Sponsor

Oslo University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT04609423

Collaborator

University of Oslo (Other), Norwegian Institute of Public Health (Other)

47,210

Enrollment

Location

Arms

6.7

Actual Duration (Months)

7043.9

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Covid-19 Respiratory Tract Infections	Dietary Supplement: Cod liver oil Dietary Supplement: Corn oil (placebo)	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

47210 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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 ratioA 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:

Quadruple (Participant, Care Provider, Investigator, Outcomes 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.

Primary Purpose:

Prevention

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

Actual Study Start Date :

Nov 10, 2020

Actual Primary Completion Date :

Jun 2, 2021

Actual Study Completion Date :

Jun 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cod liver oil supplementation for 6 months	Dietary Supplement: Cod liver oil 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. Other Names: 10 ug of vitamin D and 1 g n-3 LCPUFA Tran
Placebo Comparator: Corn oil (placebo) supplementation for 6 months	Dietary Supplement: Corn oil (placebo) 5 ml of corn oil per day for 6 months x 1 time/day together with the first meal of the day

Arm

Intervention/Treatment

Experimental: Cod liver oil

supplementation for 6 months

Dietary Supplement: Cod liver oil

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.

Other Names:

10 ug of vitamin D and 1 g n-3 LCPUFA

Tran

Placebo Comparator: Corn oil (placebo)

supplementation for 6 months

Dietary Supplement: Corn oil (placebo)

5 ml of corn oil per day for 6 months x 1 time/day together with the first meal of the day

Outcome Measures

Primary Outcome Measures

Number of participants diagnosed with serious Covid-19 [6 months]
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 [6 months]
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 [6 months]
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 [6 months]
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 [6 months]
Number of participants hospitalized wholly or partly caused by Covid-19.
Number of participants in Intensiv Care Unit (ICU) caused by Covid-19 [6 months]
Number of participants with ICU care wholly or partly caused by Covid-19.
Number of participants with any admissions to hospital [6 months]
Number of participants with any admissions to hospital based on the Norwegian Patient Registry data.
Infection with each of the mentioned pathogens [6 months]
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 [6 months]
Based on The Norwegian Reimbursement Database
Number of visits at GP [6 months]
Based on The Norwegian Reimbursement Database

Other Outcome Measures

Incidence of Cardiovascular disease [6 months]
Based on self-reporting and Norwegian Registries
Incidence of Cardiovascular disease [30 months]
Based on self-reporting and Norwegian Registries
Incidence of cardiovascular mortality [6 months]
Based on self-reporting and Norwegian Registries
Incidence of cardiovascular mortality [30 months]
Based on self-reporting and Norwegian Registries
Incidence of cancer [6 months]
Based on self-reporting and Norwegian Registries
Incidence of cancer [30 months]
Based on self-reporting and Norwegian Registries
Incidence of cancer mortality [6 months]
Based on self-reporting and Norwegian Registries
Incidence of cancer mortality [30 months]
Based on self-reporting and Norwegian Registries
All-cause mortality [6 months]
Based on self-reporting and Norwegian Registries
All-cause mortality [30 months]
Based on self-reporting and Norwegian Registries
Incidence of fracture of the hip or forearm [6 months]
Based on self-reporting and Norwegian Registries
Incidence of fracture of the hip or forearm [30 months]
Based on self-reporting and Norwegian Registries
Incident dementia [6 months]
Based on self-reporting and Norwegian Registries
Incident dementia [30 months]
Based on self-reporting and Norwegian Registries
Number of participants diagnosed with serious Covid-19 [12 months]
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 [12 months]
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.
Laboratory confirmed respiratory tract infection [12 months]
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.
Self-reported airway infection [12 months]
The number of episodes with any two of the following symptoms: fever, cough, nasal congestion or sore throat
Number of participants with self-reported cod liver oil related adverse events [12 months]
Number of participants with self-reported adverse events
Number of participants with cod liver oil related adverse events [12 months]
Number of participants hospitalized for major diseases or death in the cod liver oil versus placebo group in Norwegian registries

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.