Clinical trial NCT05121766
Conditions: COVID-19
Keywords: post-acute sequelae of covid-19 post- covid syndrome long covid syndrome healthcare workers post-covid symptoms quality of life omega-3
Sponsor: Hackensack Meridian Health
Start date: 2022-01-10; Completion date: 2023-04-21
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a two-arm, double blind randomized 12-week study to supplement omega-3 (Eicosapentaenoic acid - EPA + docosahexaenoic acid - DHA) among 100 adults (age 18+) who had coronavirus-19 (covid-19) and are experiencing possible after-effects from post-acute sequelae of covid-19 (also called post-covid syndrome or long covid syndrome).

Detailed description:
This is a double-blind, randomized controlled trial (RCT) with two treatment arms:

Arm 1 - Omega-3 (Eicosapentaenoic acid - EPA + docosahexaenoic acid - DHA) - Dose is 2,100mg per day via 3 mini-capsules, 2x/day (a total of 6 mini-capsules per day). Each capsule has 252mg of EPA and 102mg of DHA.

Support for dosing:

* The American Heart Association (AHA) says taking up to 3 grams of fish oil daily in supplement form is considered safe;
* Up to 5,000mg of omega-3 fatty acids per day is considered safe;
* The U.S. Food and Drug Administration recommends consuming no more than 3 g/day of EPA and DHA combined, including up to 2 g/day from dietary supplements.

Arm 2 - Placebo - made from soybean oil (same dosing schedule as intervention arm)

Arms: arm 1: Omega-3 (EPA+DHA) - Dose is 2,100mg per day via 3 mini-capsules, 2x/day (a total of 6 mini-capsules per day). Each capsule has 252mg of EPA and 102mg of DHA. arm 2: 3 Soybean Oil Placebo capsules 2x/day (a total of 6 mini-capsules per day).
Interventions: intervention 1: Omega-3 (EPA+DHA) intervention 2: Placebo
Intervention descriptions: intervention 1: Dose is 2,100mg per day via 3 mini-capsules, 2x/day (a total of 6 mini-capsules per day).

Each capsule has 252mg of EPA and 102mg of DHA. intervention 2: 3 Soybean Oil Placebo capsules

Protocol documents:
Prot_SAP_000.pdf: 
1 
 
 
 
 
Feasibility Pilot Clinical Trial of Omega-3 (EPA+DHA) 
Supplement vs. Placebo for Post-Acute Sequelae of COVID-19 
Recovery among Health Care Workers  
 
 
Short Title: Covid Recovery Study 
Investigational Product: OceanBlue Omega-3 EPA+DHA Supplement (KD Pharma) 
Principal Investigator: Arunima Sarkar, MD, FACP, CMD - HMH Center for Healthy 
Senior Living 
 
Sub-Investigators:  
● Manisha Parulekar, MD – HMH Center for Healthy Senior Living, Dept. of 
Geriatrics 
● Chinwe Ogedegbe, MD, MPH, FACEP 
● Portia Chinnery, BSN, RN, CEN, CPPS 
● Erin Speiser, PhD, MA, CCRP  
 
 
 
 
 
 
 
 
 
 
 
NCT05121766 
August 12, 2022 


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Table of Contents 
 
1.0 Study Summary……………………………………………………………………………..3 
2.0 Objectives……………………………………………………………………………………5 
3.0 Background & Rationale…………………………………………………………………...5 
4.0 Study Endpoints………………………………………………………………………...…11 
5.0 Study Intervention/Investigational Agent…………………………………………...…..11 
6.0 Procedures Involved………………………………………………………………………11 
7.0 Data and Specimen Banking………………………………………………………..…...14 
8.0 Sharing of Results with Subjects………………………………………………….……..15 
9.0 Study Timelines……………………………………………………………………….…..16 
10.0 Inclusion and Exclusion Criteria………………………………………………….…..16 
11.0 Vulnerable Populations…………………………………………………………….....17 
12.0 Local Number of Subjects…………………………………………………………….17 
13.0 Recruitment Methods………………………………………………………………….17 
14.0 Withdrawal of Subjects………………………………………………………………..18 
15.0 Risks to Subjects………………………………………………………………………18 
16.0 Potential Benefits to Subjects……………………………………………………..….20 
17.0 Data Management and Confidentiality………………………………………………21 
18.0 Informed Consent Process…………...………………………………………………23 
19.0 Adverse Event Reporting and Monitoring…………………………………………...23 
20.0 Ethical Considerations and Trial Administration……………………………………25 
References…………………………………………………………………………………27 
Appendix A: Inclusion/Exclusion Survey………………………………………………..32 
Appendix B: Demographic/Baseline Survey……………...……………………...…….35 
Appendix C: Symptoms & Quality of Life Post Covid Survey……………………..….38 
Appendix D: Follow-up Feasibility Survey & Study Discontinuation Verification…...42 
Appendix E: Omega-3 Supplement & Labeling Info…………………………….….…46 
 
 


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1.0 
Study Summary 
 
Study Title 
HMH Omega-3 Covid Recovery Study 
 
Study Design 
We will conduct a two-arm, double blind randomized 
12-week study to supplement omega-3 (EPA + DHA) 
among 100 adults (age 18+) who had covid-19 and are 
experiencing possible after-effects from the illness 
(post-acute sequelae of covid-19, also called post-
covid syndrome or long covid syndrome). 
Primary Objective 
The primary objective is to serve as a feasibility study 
for omega-3 fatty acid supplementation v. placebo in 
adult patients to limit long covid syndrome.  
This will serve as a proof-of-concept for a larger follow-
up study to subsequently be conducted. 
Secondary 
Objective(s) 
Determine which of the post-covid symptom(s) are 
most impacted by omega-3 supplement.  
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
Participants will be assigned to one of two study arms 
and asked to take an Omega-3 supplement or placebo 
for 12 weeks. Participants will report symptoms bi-
weekly throughout the study period. A spot blood 
sample to assess omega-3 levels will be done at 
baseline and at the end of the 12-week study period. 
 
A survey will be used bi-weekly to assess health status 
and outcomes via patient self-report. Data on 
demographics and comorbidities such as obesity and 
diabetes will be collected at baseline. At the end of 
study participation, subjects will take a follow-up survey 
assessing feasibility.  
IND/IDE #  
 IND # 157250 
Study Population 
Hackensack Meridian Health team members age 18+ 
who tested positive for COVID-19 28+ days prior and 
who are not already taking an Omega-3 supplement.  
Sample Size 
50 participants in each arm = 100 total for final analysis 
(up to 60 participants in each arm will be recruited if 
needed, dependent on attrition for a total of up to 120) 
Study Duration for 
individual 
participants 
Individual participants will be in the study for 12 weeks. 
During the 12 week study period, subjects will be sent 
a survey every two weeks. At the end of the 12 weeks, 
subjects will complete a short survey collecting 
feasibility and acceptability data.  
Study Specific 
Abbreviations/ 
Definitions  
● Hackensack Meridian Health (HMH) 
● Center for Healthy Senior Living (CHSL) 


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2.0 Objectives 
Primary Objective 
To determine the feasibility of a clinical trial for omega-3 supplementation v. placebo in 
medical center team members for post-covid recovery.  
This will serve as a proof-of-concept for a future, grant-funded study to evaluate the 
efficacy of omega-3 supplementation among a larger population recovering from covid-
19.    
Secondary Objective 
To determine which symptoms of long covid syndrome (if any) are most affected by 
taking an omega-3 supplement.  
 
3.0 Background 
 
Supplement Interventions for Recovery of Post-Acute Sequelae of Covid-19 (Long 
Covid Syndrome) 
 
Since COVID-19 launched a worldwide pandemic in December 2019, non-prescription 
interventions have been and continue to be explored to limit the effects of the virus. As 
COVID-19 is novel, few studies on nutritional interventions have been completed. Much 
of the literature focuses on the breadth of possible or potential nutrition-based 
measures, including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin 
E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium [1]. Numerous 
analyses focus on Vitamin D, Vitamin C, and zinc [2,3,4 ].  Vit. D has been found to 
inhibit viral replication and have anti-inflammatory and immune-modulating effects, but 
as with other supplements used for prophylaxis, controlled trials specific to COVID-19 
are needed [2, 4]. One longitudinal study in the UK, announced in June 2020, is 
examining Vit D status of 12,000 adults over the 2020-21 winter and will include a sub-
analysis to determine if minority ethnic groups are more adversely affected [4]. Another 
study suggests that 2,000-5,000 IU of Vitamin D daily for older adults with Parkinson’s 
disease (PD) may slow PD progression and have a protective effect against COVID-19 
[5]. All of these studies, however, address active covid-19 infection, not the potentially 
long recovery period afterwards that is gaining worldwide attention.  
 
The NIH has termed this symptomatic recovery period “Post-acute Sequelae of Covid-
19” or “Long Covid Syndrome.” To address this, NIH held its first workshop dedicated to 
the topic in December 2020 [6]. From severe hospitalized cases to mild outpatient 
cases, the road to recovery is complex and not yet well understood, though a few 
studies published thus far provide insights and researchers are beginning to study what 
interventions may be beneficial.  
 
These patients, also known as long-haulers or those with post covid syndrome, have 
been shown to suffer from after-effects for 12+ weeks after contracting the virus. Effects 
may be most severe in patients with underlying lung disease such as asthma and/or 
who had a more severe form of covid-19, including those hospitalized. However, even 


6 
 
those having initially recovered from a mild case of the virus report long-term effects [7].  
 
Long-term effects of covid-19 include loss of taste, loss of smell, continued need for 
oxygen therapy, and more. One New Jersey-based study on 183 patients from 
Hackensack University Medical Center found that at 35 days after discharge from the 
hospital following treatment for covid-19, 55% reported fatigue, 45.3% dyspnea, and 
51% muscular pain, among other symptoms [8]. For some, post-covid syndrome lasts 
several weeks, while for others it may last several months. A small number of patients 
are thought to perhaps never return back to their pre-covid baseline.  
 
According to the Mayo Clinic [7], the most common signs and symptoms of long covid 
syndrome are:  
● Fatigue 
● Shortness of breath 
● Cough 
● Joint pain 
● Chest pain 
 
Mayo Clinic states other long-term signs and symptoms may include: [7] 
● Muscle pain or headache 
● Fast or pounding heartbeat 
● Loss of smell or taste 
● Memory, concentration or sleep problems 
● Rash or hair loss 
● Organ damage, in particular: 
o “Heart. Imaging tests taken months after recovery from COVID-19 have 
shown lasting damage to the heart muscle, even in people who 
experienced only mild COVID-19 symptoms. This may increase the risk of 
heart failure or other heart complications in the future. 
o Lungs. The type of pneumonia often associated with COVID-19 can cause 
long-standing damage to the tiny air sacs (alveoli) in the lungs. The 
resulting scar tissue can lead to long-term breathing problems. 
o Brain. Even in young people, COVID-19 can cause strokes, seizures and 
Guillain-Barre syndrome — a condition that causes temporary 
paralysis. COVID-19 may also increase the risk of developing Parkinson's 
disease and Alzheimer's disease.” [7] 
● Blood clots and blood vessel issues 
o “COVID-19 can make blood cells more likely to clump up and form clots. 
While large clots can cause heart attacks and strokes, much of the heart 
damage caused by COVID-19 is believed to stem from very small clots 
that block tiny blood vessels (capillaries) in the heart muscle. 
o Other parts of the body affected by blood clots include the lungs, legs, 
liver and kidneys. COVID-19 can also weaken blood vessels and cause 


7 
 
them to leak, which contributes to potentially long-lasting problems with 
the liver and kidneys.” [7] 
 
● Mood and fatigue issues 
o “People who have severe symptoms of COVID-19 often have to be treated 
in a hospital's intensive care unit, with mechanical assistance such as 
ventilators to breathe. Simply surviving this experience can make a person 
more likely to later develop post-traumatic stress syndrome, depression 
and anxiety. 
o Because it's difficult to predict long-term outcomes from the new COVID-
19 virus, scientists are looking at the long-term effects seen in related 
viruses, such as the virus that causes severe acute respiratory syndrome 
(SARS). 
o Many people who have recovered from SARS have gone on to develop 
chronic fatigue syndrome, a complex disorder characterized by extreme 
fatigue that worsens with physical or mental activity, but doesn't improve 
with rest. The same may be true for people who have had COVID-19.” [7] 
 
It must be noted that other long-term health effects of covid-19 are continually being 
discovered, so the list of symptoms may change over time. A UK study of 100 patients 
who recovered from covid-19 found that 4-8 weeks after hospital discharge, 72% of 
those who had been in the ICU reported ongoing fatigue, breathlessness (65.6%), 
psychological distress (46.9%) and a 68.8% drop in EQ5D (quality of life). For those not 
in the ICU, 60.3% reported continued fatigue, breathlessness (42.6%), psychological 
distress (23.5%) and a 45.6% reduction in EQ5D [9]. A study in France of 120 patients 
hospitalized for covid and studied approximately 110 days after admission, found that 
the “most frequently reported persistent symptoms were fatigue (55%), dyspnoea 
(42%), loss of memory (34%), concentration and sleep disorders (28% and 30.8%, 
respectively)” [10]. There were no statistically significant differences between ICU and 
non-ICU patients. Measures of mobility, self-care, pain, anxiety or depression and usual 
activity were also similar, except for a “slight difference in pain in the ICU group” [10].  
 
Even in younger (age 18-34) patients who were never hospitalized, a CDC phone 
survey found 1 in 5 were not back to their previous healthy state 14-21 days after 
testing positive [11].  
 
Inflammation may be a common thread with multiple effects from long covid syndrome. 
A common complaint is “brain fog” or challenges with thinking clearly, which may be 
related to post-covid fatigue linked to ongoing inflammation [12]. Physicians report 
ongoing inflammation of the brain and nervous system, resulting in a cascade of effects 
including toxicity and dysregulation [13]. One of the more prevalent effects is seen in a 
study reported in JAMA Cardiology. It found 78 of 100 recently recovered covid patients 
in Germany had cardiac issues as seen on cardiovascular magnetic resonance (CMR) 
imaging, while 60 had ongoing myocardial inflammation [14].  
 
 
One of the challenges with long covid syndrome is that the length of time it lasts is not 


8 
 
yet known, and could span from weeks to years [12]. A study of 143 patients in Rome, 
Italy who had been hospitalized with covid and recovered, found that 87.4% had at least 
one persistent symptom [15]. In particular, 53.1% still reported fatigue, 43.4% had 
dyspnea (breathing difficulties), 27.3% reported joint pain, and 21.7% had chest pain 
[15].  
 
The Rome-based study team, located at the Fondazione Policlinico Universitario A. 
Gemelli IRCSS, asserts that geriatricians are best able to manage the multidisciplinary 
needs of post-covid patients: “In fact, the geriatrician is the specialist who best can 
manage the multidimensional health problems, with a great aptitude and skill to cope 
multimorbid and complex patients. Second, geriatricians are the doctors who best know 
the principles of teamwork in close collaboration with the other health care professionals 
and family. In particular, the geriatrician is able to manage the onset of the most 
important syndromes, such as sarcopenia, malnutrition, depression, and delirium.” [16] 
 
The study outlined in this protocol is managed by a geriatric team from the Center for 
Healthy Senior Living (CHSL) at Hackensack University Medical Center in Hackensack, 
New Jersey. 
 
 
Omega-3 Supplementation 
 
The Covid-19 infection is characterized by a very strong inflammatory response of the 
body and often results in a “Covid-19 pneumonia”, similar to what is known as Acute 
Respiratory Distress Syndrome (ARDS). Pharmacotherapies that moderate 
inflammation in ARDS/Covid-19 pneumonia are lacking. 
 
It is known that Covid-19 infection can cause severe pneumonia inflammation, triggering 
a pro-inflammatory “cytokine storm” expressed through a high expression of IL-6 and 
tumor necrosis factor (TNF), subsequent release of pro-inflammatory prostaglandin E2 
(PG), 5-lipoxygenase (LOX) and leukotrienes. High levels of free nitric oxide (NO)-
radicals causing oxidative stress and damage to the cell tissue. Additionally, at the late 
stage of the disease, neo angiogenesis has been seen to be a crucial step of lung 
fibrosis, leading finally to a fatal ARDS condition. 
 
The effects of omega-3 fatty acids, in particular EPA, on the many different 
inflammatory pathways have been well studied and described in the literature [17]. 
Many of these papers discuss the anti-inflammatory effects of the omega-3 fatty acids in 
relation to cancer development and treatment [17] and inflammatory bowel disease 
such as ulcerative colitis. Although these inflammatory disorders have nothing to do with 
Covid-19, the basic principle of inflammatory response and anti-inflammatory pathways 
within our body cells is highly likely to be the same, whether we focus on ulcerative 
colitis, colon cancer, rheumatoid arthritis or “Covid-19 pneumonia”. 
 
It is well known that the pro-inflammatory eicosanoids are derived from a 
polyunsaturated omega-6 fatty acid called Arachidonic Acid (AA) through the 


9 
 
cyclooxygenase (COX-), LOX- and p450 epoxygenase pathway. These pro-
inflammatory eicosanoids: 
● increase the vascular permeability 
● promote platelet aggregation 
● recruit neutrophils 
● cause edema 
● release pro-inflammatory substrates such as cytokines which in turn lead to the 
production of chronic inflammatory mediators like IL-1ß, IL-6, IL-8 and TNFα 
 
The same COX and LOX enzyme-systems are responsible for converting the omega-6 
arachidonic acid into pro-inflammatory eicosanoids or alternatively the omega-3 EPA 
into anti-inflammatory eicosanoids. Thus, there is a strong competitive interaction 
between the AA and EPA with COX- or LOX enzyme systems in the body cells. If the 
concentration of AA is dominant, then more pro-inflammatory eicosanoids are 
generated. However, if there is more EPA present, then more anti-inflammatory 
eicosanoids are produced and the intensity of an inflammatory attack is reduced. 
Both AA and EPA originate from our diet. A diet rich in red meat, milk, milk products, 
cheese and eggs combined with the use of omega-6 rich vegetable oils like sunflower or 
corn oil will result in a high concentration of pro-inflammatory arachidonic acid in the cell 
membranes. A diet rich in fatty fish (sardines, anchovy, salmon, mackerel, tuna) in 
combination with neutral vegetable oils like olive oil will result in a more equilibrated 
ratio of omega-6 to omega-3 in the cell membranes. EPA partly displaces AA in our cell 
membranes [18,19] and reduces the formation of pro-inflammatory cytokines [20]. 
 
 
Rationale 
Marine derived omega-3 polyunsaturated fatty acids (PUFA) supplementation have 
been shown to have a significant lowering effect on C-reactive protein, IL-6 and TNF 
which slows down the AA cleavage from the cell membrane and subsequent synthesis 
of COX/LOX generated pro-inflammatory eicosanoids [21]. Furthermore, by 
downregulating the NFkß with help of the EPA dependent IKKß-complex not only less 
IL-6 is expressed but also less vascular endothelial growth factor (VGEF), which in turns 
reduces the neo angiogenesis activity, a suppression highly desired during the Covid-19 
pneumonia infection, and which may be beneficial in reducing ongoing symptoms of 
post-covid syndrome. 
 
Nitric oxide (NO), a free radical derived from L-arginine by nitric-oxide-synthase (NOS) 
is proposed to play an important role in many inflammation processes and leads to 
severe inflammation related tissue damage. The oxidative stress triggered by NO may 
also additionally activate NFkß [22] and in turn increase further the “inflammatory 
storm”. Omega-3 fatty acids, in particular EPA, is involved in several different metabolic 
pathways which down-regulate the NOS gene expression, resulting in a decreased NO 
production thus tissue damage [23]. Another important point of inflammatory down-
regulation by EPA is competitive regulation of the COX-2 system. If the cell membrane 
contains a high content of EPA, then the probability that an EPA molecule connects with 


10 
 
the COX-2 system and generates anti-inflammatory eicosanoids is much higher than in 
the case that the pro-inflammatory AA dominates in the cell membrane [24]. 
 
Additionally, EPA is converted in the body to very potent pro-resolving mediators 
(PRMs) known as resolvins, protectins and maresins. These very active compounds 
reduce the magnitude and duration of inflammation, stimulate wound healing and 
regenerate damaged tissue. 
 
ARDS and ICU studies [25, 26, 27] of immunonutrition with omega-3 (enteral 
supplementation) after the start of hospitalization showed positive results within two 
weeks. A significant reduction in pro-inflammatory eicosanoids was evident after 24 
hours [25]. In this study, the patients received during a period of 12 hours an enteral 
nutritional supplement containing 10% fish oil. The administered dose was 0.12g/kg/h. 
Taking into consideration an average body weight of 75kg, the patients would have 
received, within the 12-hour supplementation period, a total of approximately 3 g 
Omega-3 of which roughly 2 g would have been EPA in the natural triglyceride form. 
Numerous other studies discussed in [26, 27, 28] also indicated clear benefits of an 
Omega-3/fish oil treatment for hospitalized ARDS patients, including a reduced 
mortality. The effects on long-term symptoms from covid-19 are just beginning to be 
explored among researchers, making this study among the first.  
 
 
Considerations for COVID-19 among Healthcare Workers in New Jersey 
As the densest state in America, New Jersey has been particularly hard-hit by 
coronavirus cases [29]. With 516,608 confirmed cases statewide as of January 8, 2021, 
those over age 65 have been greatly affected, comprising 16.8% of cases [30] and 
79.8% of the state’s 17,587 lab-confirmed deaths as of January 7, 2021 [30].  
 
Healthcare workers – the subject of this study – have also been devastated by the virus. 
A study of NJ healthcare workers (HCW) early in the pandemic found that these 
employees were at greater risk for becoming infected than non-healthcare workers [31]. 
A 7.3% prevalence of infection was found among NJ healthcare workers versus 0.4% 
among non-healthcare workers [31]. Infections were particularly high among Black, 
Latino and “other” races [31]. The study acknowledged that further research is needed 
“to examine whether racial differences in COVID-19 among HCW may be related to 
their particular roles in the health care setting or are reflective of residence in 
communities that are more vulnerable to infection.”[31] More recent news attests to NJ 
team members continuing to fall ill, including over 100 at Hackensack Meridian Ocean 
Medical Center in December 2020 [32]. Statistical analysis in our study will examine 
demographic information such as race and occupational role.  
 
 
4.0 Study Endpoints 
4.1 Primary Outcome Variables 
The primary endpoint is evaluation of feasibility and acceptability of omega-3 


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supplementation v. placebo to limit post-covid syndrome among adult patients. The 
Follow-up Feasibility Survey (Appendix D) will be used for this analysis.  
 
4.2 Secondary and Exploratory Outcome Variables  
A separate analysis will be conducted to determine which post-covid symptom(s) are 
more impacted by omega-3 supplement. The Bi-weekly Symptoms and Quality of Life 
Post Covid-19 Survey (Appendix C) includes the four symptoms being measured 
(respiratory, fatigue, lack of taste, lack of smell). Therefore, this bi-weekly survey will be 
used for this efficacy analysis.  
 
5.0 Study Intervention / Investigational Agent 
The investigational product is EPA+DHA, an omega-3 supplement manufactured by KD 
Pharma.  
 
 
6.0 Procedures Involved 
 
6.1 Study Design 
This is a double-blind, randomized controlled trial (RCT) with two treatment arms:  
Arm 1 - Omega-3 (EPA+DHA) – Dose is 2,100mg per day via 3 mini-capsules, 2x/day 
(a total of 6 mini-capsules per day). Each capsule has 252mg of EPA and 102mg of 
DHA.  
 
Support for dosing: 
     - The American Heart Association (AHA) says taking up to 3 grams of fish oil daily in 
supplement form is considered safe [33] 
     - Up to 5,000mg of omega-3 fatty acids per day is considered safe [34].      
     - The U.S. Food and Drug Administration recommends consuming no more than 3 
g/day of EPA and DHA combined, including up to 2 g/day from dietary supplements.[35] 
 
Arm 2 - Placebo – made from soybean oil (same dosing schedule as intervention arm) 
 
Supplement and placebo will be supplied by KD Pharma.  
 
 
6.2 Research Procedures  
For an overview of the study, please see figure 1 below.  
1. Team members who email the study team at the address on the flyer will be sent an 
eligibility survey in REDCap to determine if study inclusion criteria are met.  
2. Those who meet study inclusion criteria will then be sent the study consent form in 
REDCap, and encouraged to call or email the study team with questions. 


12 
 
3. If the patient expresses further interest in study participation, s/he will be consented 
via REDCap and then will be sent a link to the baseline survey in REDCap.  
4. Upon consent, RC will assign ID# and enter the subject into REDCap (study data 
management system).  
5. Subjects will be randomly assigned to receive 3 Omega-3 (EPA+DHA) mini-capsules 
twice daily (total of 2,100mg per day) for 12 weeks in the experimental intervention arm 
or three placebo mini-capsules twice daily for 12 weeks.  
● Study supplement or placebo are supplied at no cost to the subject and 
will be mailed to the subject’s home. 
● Study subjects will receive two shipments over the course of study 
participation. 
○ Package 1 upon enrollment 
○ Package 2 at the end of week 4 
● Subjects will also receive, in these shipments, two spot blood sample tests 
for omega-3 levels, and directions indicating when to use the test kits. 
6. All study subjects in each arm will be asked to give a spot sample (2 drops) of blood 
at baseline and again after 12 weeks (end of study participation). This will be done 
using OmegaQuant test kits that are mailed to the subject’s home. The de-identified 
samples will be mailed by the subject in the provided envelope to OmegaQuant Lab, 
associated with University of South Dakota Medical Center, for analysis of omega-3 
levels. These tests involve no cost to the subject. Subjects will be informed of their 
omega-3 level after results are returned from the lab and the subject’s participation in 
the study is complete.  
7. Monitoring of Subjects:  
● Subjects will be encouraged to call RC at any time with study questions. RC will 
also call each subject weekly to ensure procedures are being followed and 
answer any questions. The weekly “check-in call” will occur for 12 weeks. 
● Each subject will be checking their blood pressure. Subjects will report their blood 
pressure via REDCap in their bi-weekly survey. Reported adverse events will be 
documented.  
● Subjects in both arms will be tracked for 3 months (12 weeks). An interim 
analysis will be done for a sub-sample (the first 20 subjects) after three weeks of 
participation to determine if any arm should be adjusted or terminated.  
● Participants will continue to receive standard of care and follow up for any routine 
conditions being managed at HackensackUMC.   
 
8. The final study activity will include the 2nd spot blood sample and a short survey 
(survey link emailed to subject via REDCap) to collect feasibility and acceptability data. 
The survey will take about 10 minutes to complete.  
 


13 
 
9. Subjects will then be mailed a $40 gift card for completing the study.  
10. Subjects will be informed of their omega-3 level after results are returned from the 
lab and the subject’s participation in the study is complete 
 
Any subject missing both daily doses 3 times a week for 3 weeks in a row will be 
removed from the study for non-compliance, and asked to dispose of any unused study 
supplement/placebo. This will be documented in a dedicated RedCap survey for anyone 
who discontinues study participation, either for non-compliance or of their own will.  
Any subject who has another covid-19 infection during study participation may continue 
on the study. The RC will inform the subject of this if/when any subject reports a new 
covid infection.  
 


14 
 
Figure 1: Study Schema 


15 
 
7.0 Data and Specimen Banking 
 
7.1 Data or specimens for future use 
Each subject will have two blood specimens collected for analysis of omega-3 levels. 
Those specimens will not be banked for future use after this study.  
Data collected from questionnaires will be stored on the HMH REDCap database on the 
HMH server. Data will be stored for six years after the end of the study. Access to the 
data will be restricted to the study staff.  
 
7.2 Data to be stored or associated with each specimen 
For each subject who has the 2 blood specimens taken, only the test result will 
be stored – together with the other study data - for six years per HMH policy. As 
the consent form indicates, “Spot blood samples will not be used for future 
research. The samples will be destroyed by Omega Quant Labs approximately 
two weeks after analysis.” 
 
7.3 Procedures to release data or specimens 
In order to access data, a research proposal that describes the intended use of the data 
must be submitted and approved by the PI. Anyone requesting access to data must 
obtain IRB approval and demonstrate secure data storage prior to receiving a de-
identified data set. Access to the data is limited to non-commercial use. 
 
8.0 Sharing of Results with Subjects 
Individual-level data (the results of both COVID-19 tests and the omega-3 levels from 
the blood draw if applicable) will be shared with participants. The major findings of the 
study and aggregate data, will be shared with participants after the study has 
concluded. 
1) Unblinding will occur when a subject drops out of the study due to an adverse event. 
The subject will be informed of their study arm assignment via email so that they can 
better understand any possible adverse reaction to the study medication.  
2) Subjects who complete the study will be unblinded and informed of their study arm 
assignment via email after the study team has seen their data (descriptive statistics 
generated by RedCap). This will be done within 4 weeks of each subject finishing the 
study. 
The study coordinator will inform each subject when they finish study participation, to 
expect an email advising which study arm they were in.  
 
 


16 
 
 
 
 
 
 
 
 
 
 
 
9.0 Study Timelines 
Each subject will spend 12 weeks in the study.  
It is anticipated that all subjects will be enrolled within a 6-month timeframe.  
 
 
Month 
1 
Month 
2 
Month 
3 
Month 
4 
Month 
5 
Month 
6 
Month 
7 
Month 
8 
Month 
9 
Month 
10 
Month 
11 
Month 
12  
IRB 
approvals 
& startup 
 
 X 
       
X 
          
   X 
 
 
 
 
 
 
 
 
 
Enroll-
ment 
 
 
 
     
  X 
   X 
   X 
  X 
  X 
  X 
   
 
 
Subjects 
on study 
(12 
weeks) 
 
 
 
 
 
  X 
 
 
   X 
 
 
 
  X 
 
 
  X 
 
 
  X 
 
 
  X 
 
 
   X 
 
 
  X 
 
 
  X 
 
Interim 
analysis  
at 3 
weeks 
 
 
 
 
 
  X 
 
 
 
 
 
   
   
   
Final data 
analysis 
 
 
 
 
   
    
 
 
 
 
  X 
  X 
  X 
 
 
10.0 Inclusion and Exclusion Criteria 
 
Inclusion Criteria  
- Team member at Hackensack Meridian Health  
- Age: 18+ 
- Willing to provide informed consent 
- Formal diagnosis of COVID-19 via PCR test (if home test was done, team member 
must confirm via PCR test) 
-Outpatient treatment only for covid-19; no hospitalization (most team members will be 
vaccinated and may likely have milder case) 
- Must be experiencing 1+ ongoing covid-19 symptom being measured in this study 
(respiratory symptoms (shortness of breath, cough), fatigue, loss of taste, loss of smell)  
-Symptom(s) have persisted for more than 12 weeks after initial infection 


17 
 
-Symptom(s) coincided with covid-19 infection and were not present prior to covid-19 
infection  
- Does not have soy allergy 
- Does not have allergy to fish 
- Able to participate in bi-weekly surveys in REDCap 
- Able to take own blood pressure and record it in bi-weekly REDCap survey 
- Willing to participate in 12-week study and be assigned to either intervention or 
placebo arm 
- Not currently taking an omega-3 supplement or other high-dose supplement (over 
2,000 IU) with potential for aiding recovery of long covid syndrome (e.g. zinc, Vit C, 
Elderberry).  
-Able to take/swallow six mini-pills daily 
-Able and willing to give a spot blood sample (2 drops) at baseline and end of study.   
 
Exclusion Criteria 
- Not a Team Member at Hackensack Meridian Health 
- Not age 18+ 
- Unwilling to provide informed consent/ declined to take part  
- No formal diagnosis of COVID-19 via PCR test (if home test was done, team member 
must confirm via PCR test) 
-Were hospitalized for treatment of covid-19 
- Not experiencing 1+ ongoing covid-19 symptom being measured in this study 
(respiratory symptoms (shortness of breath, cough), fatigue, loss of taste, loss of smell)  
-Symptom(s) have persisted for more than 12 weeks after initial infection 
-Symptom(s) did not coincide with covid-19 infection and were present prior to covid-19 
infection  
- Does have soy allergy  
- Does have allergy to fish 
- Not able to participate in bi-weekly surveys in REDCap 
- Not able to take own blood pressure and record it in bi-weekly REDCap survey 
- Not willing to participate in 12-week study and be assigned to either intervention or 
placebo arm 
- Currently taking an omega-3 supplement or other high-dose supplement (over 2,000 
IU) with potential for aiding recovery of long covid syndrome (e.g. zinc, Vit C, 
Elderberry).  
-Unable to take/swallow six mini-pills daily 
-Not able and not willing to give a spot blood sample (2 drops) at baseline and end of 
study. 
 
11.0 Vulnerable Populations 
Subjects will be age 18+ and must be actively employed by HMH in order to participate 
in the study.  


18 
 
Hackensack Meridian Health is dedicated to creating an inclusive environment that 
delivers culturally competent, patient-centered care. We value and celebrate the 
contribution of our team members and acknowledge that everyone deserves to be 
treated with dignity and respect.Through the Diversity & Inclusion program, we strive to: 
● Foster an inclusive environment that embraces different perspectives and that 
values the contributions of each individual 
● Promote diversity at every level throughout our network 
● Employ and develop the finest talent from all groups within our vibrant 
communities 
● Provide outstanding and award-winning health care services 
Through the Team Member Resource Group (TMRG) strategic initiative of Diversity & 
Inclusion, team members can link up with coworkers from similar backgrounds and 
identities to make a difference in the workplace and help achieve their goals. Current 
TMRGs include the Multiracial Resource Group, Aspiring Women Leaders, Women in 
Leadership, Pride & Allies, Veterans, and Young Professionals. 
To foster diversity in study enrollment, the recruitment flyer will be sent specifically to 
these TMRGs for targeted distribution.  
 
12.0 Local Number of Subjects 
The number of subjects will be 50 in each of two arms, for a total of 100 subjects for 
analysis. Up to 60 participants in each arm will be recruited if needed, dependent on 
attrition, for a total of up to 120 subjects.  
 
 
Study Site(s) 
Research activities will take place remotely as indicated. Specifically, subjects will:  
-have study meds delivered to them 
-will complete eConsent in REDCap  
-will have the omega-3 level test kits mailed to their home, will complete the spot blood 
sample at home and mail directly back to OmegaQuant Lab in the mailing envelope 
provided. 
 
13.0 Recruitment Methods  
Eligible participants will be identified among adult (age 18+) team members working for 
Hackensack Meridian Health. A recruitment flyer will be sent to all team members via 
HMH employee newsletters including "The Pulse" and "One." Additionally, to foster 
diversity in study enrollment, the recruitment flyer will be sent to the Team Member 
Resource Groups (TMRGs) at HMH for targeted distribution to help ensure diversity in 
enrollment, as noted in Section 11.0.  
 
The flyer will also be placed in physician lounges across the HMH network.  


19 
 
To further expand recruitment, the study flyer will be given to the HMH Covid Call 
Center so team members who are experiencing long covid symptoms can be provided 
with the study email address. Those who receive the email address may contact the 
study team or not per their preference, and will not be followed up on by the Covid Call 
Center.  
Each potential subject will access a link to an eligibility survey to determine if they meet 
inclusion criteria.  
They will be given the opportunity to ask any questions by contacting a member of the 
study team. If the team member is interested, they will access the informed consent 
form in REDCap and be asked to either sign it and participate or download a copy to 
review on their own time. If they later choose to participate, they can continue with 
informed consent in REDCap.  
Alternatives to participation include that subjects may choose to consult their healthcare 
provider for help addressing their symptoms. Subjects may also take a supplement(s) 
on their own at any time. 
 
14.0 Withdrawal of Subjects 
If a subject needs to be withdrawn from the study without their consent for medical 
reasons or non-compliance, she or he will be notified by Dr. Sarkar or Dr. Parulekar by 
phone, with a follow-up letter mailed to the subject’s home. 
If a subject chooses to withdraw from the study, she or he must notify the PI by calling 
the phone number on the consent form. All data collected up to the point of termination 
will be kept in the study. 
 
Any subject missing both daily doses 3 times a week for 3 weeks in a row will be 
removed from the study for non-compliance, and asked to dispose of any unused study 
supplement/placebo. 
 
 
15.0 Risks to Subjects and Monitoring Plan 
8 Possible Risks from Omega-3 Supplement:  
Risk #1: Taking large amounts of fish oil can inhibit blood clot formation, which may 
increase the risk of bleeding and cause symptoms such as nosebleeds or bleeding 
gums 
Outcome - Fish oil supplementation did not increase perioperative bleeding [36] 
Outcome - The present overview found no support for discontinuing the use of n-3 fatty 
acid treatment before invasive procedures or when given in combination with other 
agents that affect bleeding [37]. 
Monitoring Plan for bleeding risk: Plan: As bleeding risk is low, we do not need to adjust 
any medications. We will add a follow up question for each subject, asking: “any 
bleeding?”  


20 
 
Risk #2: One small study, for example, found that taking 8 grams of omega-3 fatty acids 
per day led to a 22% increase in blood sugar levels in people with type 2 diabetes over 
an eight-week period [38].  
Taking high doses of omega-3 fatty acids can stimulate glucose production, which may 
lead to increased blood sugar — though the scientific evidence is not conclusive.   
Monitoring Plan for Hyperglycemia risk: Chance is low so no need of adjustment of 
medication required, so we can skip extra monitoring 
 
Outcome - Findings from RCT trials suggest that omega-3 supplementation was unable 
to affect either plasma glucose levels or HbA1c except increased fasting glucose levels 
in Asians [39] 
Risk #3: Omega-3 fatty acids have been shown to lower blood pressure, which may 
interfere with certain medications and cause problems for those with low blood pressure 
An analysis of 31 studies concluded that taking fish oil can effectively lower blood 
pressure, especially for those with high blood pressure or high cholesterol levels [40]. 
 
Monitoring Plan for Hypotension risk: No significant drop to adjust medication. Subject 
will be asked to self-monitor blood pressure and report it in the bi-weekly survey in 
REDCap. This RedCap survey also includes a question asking team members to 
indicate the method used to take their blood pressure: “BP was taken by machine at 
home” or “BP was taken by machine at a pharmacy” or “BP was taken manually in 
medical office.”  
 
Outcome: The meta-analysis also found that among all participants who received 
omega-3s, through supplements such as fish oil, the average decrease in systolic 
pressure was 1.75 mm Hg and diastolic pressure dropped by 1.1 mm Hg, regardless of 
the person’s blood pressure status [41]. 
Risk #4: Diarrhea is a side effect of omega-3 fatty acid supplements such as fish oil and 
flaxseed oil [42].  
Monitoring Plan for Diarrhea risk: there is risk of diarrhea with omega-3, taking 
supplements with meals and consider decreasing dosage to see if symptoms persist. 
Will recommend that supplement/placebo be taken with food. [43] 
 
Risk #5: Fish oil is high in fat and may cause acid reflux symptoms such as belching, 
nausea, indigestion and heartburn in some people [44].  
Monitoring Plan for GERD risk: Plan: splitting dose into a few smaller portions 
throughout the day may help eliminate indigestion 
 


21 
 
Risk #6: Some animal studies have found that a high intake of omega-3 fatty acids 
could increase the risk of hemorrhagic stroke while other human studies have found no 
association [43] 
Monitoring Plan for Hemorrhagic stroke: not proved in humans, so will not use this for 
our study 
 
Risk #7: Caution---Certain types of omega-3 fatty acid supplements like cod liver oil are 
high in vitamin A, which can be toxic if consumed in large amounts 
Monitoring Plan for Vitamin A hypervitaminosis:  based on composition, we can also 
remove this based on our Omega 3 supplement 
 
Risk #8: Although moderate doses of fish oil have been shown to improve sleep quality, 
one case study suggests that taking large amounts caused insomnia [43]. 
Monitoring Plan for Insomnia: not including, as there is not enough evidence 
 
Summary of monitoring plan for side effects:  
1. Self-reported BP check, submitted via bi-weekly survey, using a BP machine at 
home, BP machine at a pharmacy, or manually in medical office (will indicate 
method on bi-weekly survey) 
2. Take omega 3 with meals to reduce diarrhea 
3. Ask question “any increased bleeding?” during weekly check-in call  
 
Note: Consent form will include that some interactions may occur with anticoagulants, 
and antihypertensive medications, though minimal. The consent form will also include 
that the finger prick spot blood test for omega-3 levels may cause minor soreness on 
the subject's finger. 
 
Additionally:  
EPA+ DHA is an omega-3 supplement, which are generally regarded as safe when 
given orally. Omega-3 products are approved for use in the treatment of post 
myocardial infarction, hypertriglyceridemia and as a dietary supplement in numerous 
territories worldwide, including Europe and the US. 
 
Experience with the approved preparations and clinical studies is that adverse events 
are relatively minor in nature and severity, and are primarily related to gastro-intestinal 
effects.  
 
During the study the subject will take a health survey bi-weekly and will be asked to 
report any health concerns to the PI. Reported adverse events will be documented. 
Additionally, the Research Coordinator (RC) will also call each subject weekly for the 


22 
 
duration of the study (total of 12 weeks) to ensure procedures are being followed, 
answer any questions, and refer any health issues to the PI.   
● If any individual subject experiences an adverse event (AE), the PI will  
determine whether to stop study participation for that individual. 
● If the first 10 subjects experience an AE, the study will stop. This decision will be 
made under the direction of the IRB in consultation with the DSMB as described 
below in section 19.2 Data Safety Monitoring.   
 
Risks to subjects from Soybean Oil Placebo:  
The placebo is made from soybean oil. There is an allergy risk associated with ingesting 
soy. The study eligibility criteria excludes any person with a soy allergy. 
Risks Associated with Washout:  
There are no known risks associated with washout from omega-3 supplement or the 
soybean oil placebo. 
 
16.0 Potential Benefits to Subjects 
Subjects in the omega-3 supplement arm will receive the investigational product at no 
cost. (Those in the placebo arm will receive placebo at no cost.). Participants will also 
receive two free blood spot tests measuring omega-3 levels: one at baseline, and one at 
the end of the 12 weeks of the study. 
Overall, the potential benefits to society of this feasibility study is to determine if a larger 
study on omega-3 supplementation for recovery of Long Covid Syndrome is warranted.  
 
17.0 Data Management and Confidentiality 
 
17.1 Data analysis plan  
All study data will be summarized with descriptive statistics.  Continuous variables will 
be summarized with means, standard deviations, medians and ranges.  Categorical 
variables will be summarized with counts and percentages.  Data will be summarized 
overall and separately by the two study arms: Omega-3 supplement or placebo. In 
general, continuous endpoints will be compared between groups using t-tests or 
Wilcoxon rank sum tests, as appropriate.  Categorical endpoints will be compared 
between groups using chi-square tests or Fisher’s exact tests, as appropriate. 
 
The primary analysis will be the comparison of groups on the long covid-19 symptoms 
recovery using a chi-square test or Fisher’s exact test, as appropriate.  
 
Additional exploratory analyses may be conducted to better understand relationships 
within the data. 


23 
 
Results with a p-value less than or equal to 0.05 will be considered statistically 
significant.  No adjustments for multiple comparisons will be implemented as this is a 
feasibility study not statistically powered for analyses. 
 
17.2 Steps to secure the data during storage, use, and transmission 
Participants’ identifying information will be kept separate from their demographic 
questionnaire and their other surveys for this study within REDCap. Participants’ 
responses and objective data will be linked to identifying information only through a 
unique identifier and the information used to link records with identifying information will 
be kept in a securely locked file cabinet only accessible to the study team. Electronic 
data will be stored in password protected databases on the secure Hackensack 
Meridian Health server. Identifying information will not be included on datasets used for 
statistical analysis and study progress reports. 
 
17.3 Information included in that data or associated with the specimens 
No specimens will be stored as part of this study. The only specimens collected will be 
the two spot blood samples which will be sent to OmegaQuant lab. The data will include 
variables describing participants’ survey responses, and any notes in REDCap from 12 
weekly check-in calls from the RC. 
For the two spot blood sample tests for each subject, the specimens will be coded 
before being sent to OmegaQuant Lab, associated with University of South Dakota 
Medical Center. This lab will only receive de-identified samples, and no identifying 
patient information.  
● 
Mode of data storage. 
Data collected from questionnaires will be stored on the REDCap database on 
the HMH server. Any paper files will be stored on site at HUMC in locked file 
cabinets only accessible by the study staff. 
● 
Duration of data storage. 
Data will be stored for 6 years after the end of the study, per HMH requirements. 
● 
Access to data. 
Access to the data will be restricted to the study staff. 
● 
Responsibility for receipt or transmission of the data. 
The PI will be responsible for receipt and transmission of the data. 
● 
Transportation of the data. 
The data should not need to be transported. However, if there is a need to 
transport the data, secure file transfer will be used. 
● 
Type of data being collected, stored, transmitted and shared. 
o Protected Health Information (PHI) 


24 
 
o Personally Identifiable Information (PII) 
 
● 
All computer software to protect against malware will be kept up-to-
date and  
operational. All operating system and software updates and patches 
will be applied regularly. 
● 
Codes linking participants’ identifying information with de-identified 
data will be stored separately from the corresponding data sets. 
● 
The data will only be accessed on HMH workstations and laptops such 
that encryption and password protection will be in place with two-factor authentication 
required for access. 
● 
Access to the data is limited to the study team. Any study staff added 
to the project will be approved by the PI and added to the IRB protocol. 
All HMH policies and procedures for data collection, storage, transmission and 
destruction will be followed. 
 
18.0 Informed Consent Process 
Obtaining consent: 
● 
The consent process will take place online via REDCap.  
● 
No waiting period is required between informing prospective participants and 
obtaining consent.  
● 
The study will follow the informed consent process for research. 
Process to Document Consent in Writing 
- 
The study will document participants’ informed consent in writing 
(electronically) via REDCap. 
- 
The consent document will be attached to the IRB submission. 
 
19.0 Adverse Event Reporting and Monitoring  
 
Clinical criteria for withdrawing an individual subject: Subjects may call the PI at the 
phone number listed on the consent form at any time to report any concerns which may 
or may not warrant withdrawal from the study. Additionally, the subject will receive a 
check-in call 1x per week to discuss any issues of concern. The study physicians, Dr. 
Sarkar and Dr. Parulekar, will be informed of any issues that arise which may or may 
not warrant a subject being removed from the study due to safety or toxicity concerns.  
 
19.1 Adverse Events 
19.1.1 Definitions  
Unanticipated problems involving risk to participants or others: Any incident, 
experience, outcome, or new information that: 


25 
 
1. Is unexpected; and 
2. Is related or possibly related to participation in the research; and 
3. Indicates that subjects or others are at a greater risk of harm (including physical, 
psychological, economic, legal or social harm) than was previously known or 
recognized.  
Unexpected. The incident, experience or outcome is not expected (in terms of nature, 
severity, or frequency) given the research procedures that are described in the study 
related documents, such as the IRB-approved research protocol/research plan and 
informed consent documents; and the characteristics of the subject population being 
studied. 
Related. There is a reasonable possibility that the incident, experience, or outcome may 
have been caused by the procedures involved in the research. 
Adverse event (AE): Any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have to have a causal relationship with this treatment. An AE can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of study treatment, 
whether or not considered related to the study treatment.  
Serious adverse event (SAE): Any untoward medical occurrence that, at any dose, 
results in death; is life threatening (i.e., an event in which the patient was at risk of death 
at the time of the event; it does not refer to an event that hypothetically might have 
caused death if it were more severe); requires inpatient hospitalization or prolongation 
of existing hospitalization; results in persistent or significant disability/incapacity; or is a 
congenital anomaly/birth defect.  
 
19.1.2 Reporting of AEs/SAEs 
AE will be reported and recorded from the time of the first dose of study drug through 30 
days after the last dose of study drug.  AE monitoring should be continued for at least 
30 days following the last dose of study supplement. AEs (including laboratory 
abnormalities that constitute AEs) should be described using a diagnosis whenever 
possible, rather than individual underlying signs and symptoms. When a clear diagnosis 
cannot be identified, each sign or symptom should be recorded as a separate AE. The 
Investigator should ask the patient non-leading questions to determine if any AEs have 
occurred during the study, since the last visit. AEs may also be recorded when they are 
volunteered by the patient, or through physical examination, laboratory tests, or other 
clinical assessments. An AE should be followed and an assessment should be made at 
each visit (or more frequently, if necessary) of any changes in severity of the event, the 
suspected relationship to the study treatment, the interventions required to treat the 
event, and the outcome. 


26 
 
It is the responsibility of the PI (and/or sub-investigators) to report all unanticipated 
problems involving risks to subjects or others to HMH IRB.    
For unanticipated problems/adverse events associated with clinical trials that do not 
meet the criteria in Section 19.1.1, the investigator or study team member should 
describe the events at the time of continuing review. 
 
19.2 Data Safety Monitoring 
The Hackensack Meridian Health Data and Safety Monitoring Board (DSMB) will be 
responsible for the data and safety monitoring of this trial. As this study is an 
investigator initiated feasibility study utilizing a non-FDA approved supplement for which 
the PI holds the IND it is considered a moderate risk study which requires real-time 
monitoring by the PI and study team and reviewed monthly by the HMH DSMB. 
The Principal Investigator and the Co-Investigators will review the data including safety 
monitoring at their weekly institution-based meetings and on monthly teleconferences.  
All Severe Adverse Events (SAEs) are required to be reported to the IRB. Based on 
SAEs, the IRB retains the authority to suspend further accrual pending more detailed 
reporting and/or modifications to further reduce risk and maximize the safety of 
participants.  Progress on the trial will be reviewed by the HMH DSMB monthly from the 
time the first participant is enrolled on the study. Results of the DSMB meetings will be 
forwarded to the IRB with recommendations regarding need for study closure.  DSMB 
recommendations should be based not only on results for the trial being monitored as 
well as on data available to the DSMB from other studies. It is the responsibility of the PI 
to ensure that the DSMB is kept apprised of non-confidential results from related studies 
that become available. It is the responsibility of the DSMB to determine the extent to 
which this information is relevant to its decisions related to the specific trial being 
monitored.  A written copy of the DSMB recommendations will be given to the trial PI 
and the IRB. If the DSMB recommends a study change for participant safety or efficacy 
reasons, the trial PI must act to implement the change as expeditiously as possible. If a 
recommendation is made to change a trial for reasons other than patient safety or 
efficacy, the DSMB will provide an adequate rationale for its decision. Authority to close 
a trial for safety reasons lies with the IRB, with the above described input from DSMB.   
 
 
19.3 End of Study  
The End of Study will occur when all participants have completed the 6 month follow-up 
period (i.e., when the last patient has expired, been followed for 6 months after last 
dose of study drug, been lost to follow-up, or has withdrawn consent, whichever occurs 
first). At the 6 month point, one of the study physicians or the RC will call the subject 
with a quick phone survey, captured in REDCap. 
 


27 
 
20.0 Ethical considerations and Trial Administration 
 
20.1 Institutional Review Board (IRB) Review 
The final study protocol, ICF, and surveys including data collection tools will be 
approved by the Hackensack Meridian Health Institutional Review Board (IRB). 
Approval will be received in writing before initiation of the study.  
Any changes to the study design will be formally documented in protocol amendments 
and will be approved by the IRB prior to implementation. 
 
20.2 Subject Confidentiality 
The patient collected data, and all analysis of the data will adhere to HIPAA & 
institutional patient confidentiality requirements as described above.  
More specifically, a coding system will be used for which a unique identifier (study ID 
number) will be assigned to each patient name and contact details.  Only the study 
number will be included in the data collection tool, data analysis software and potential 
publications. The list with the direct identifiers (for the purposes of linking data with the 
samples and keeping track of patients) will be stored separately in a secure server at 
each site.  
Analytical datasets will be stored on secure servers that also limit access to the 
investigator team. Should results of the study be published or reported, individual 
names or other identifying information will not be used. 
 
20.3 Data Storage/Security 
All data will be stored on a Hackensack Meridian Health password protected computer 
only accessible by the investigator team.  
Electronic data will be managed using a secure, web-based system that has user-level 
access control.  Analytical datasets will be stored on secure servers that also limit 
access to the investigator team. 
 
20.4 Retention of Records 
Records will be retained in accordance with regulatory, organizational and sponsor 
requirements, but for no less than six (6) years following the completion of the research.  
Disposal of records will be done in such a manner that no identifying information can be 
linked to research data. 
References: 


28 
 
1. BourBour F, Mirzaei Dahka S, Gholamalizadeh M, et al. Nutrients in prevention, 
treatment, and management of viral infections; special focus on Coronavirus 
[published online ahead of print, 2020 Jul 9]. Arch Physiol Biochem. 2020;1-10. 
doi:10.1080/13813455.2020.1791188 
2. Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and 
severity [published online ahead of print, 2020 Jun 20]. J Infect Public Health. 
2020;S1876-0341(20)30531-1. doi:10.1016/j.jiph.2020.06.021 
3. Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and 
Vitamin C: An Experimental, Synergistic Therapy for the Prevention and 
Treatment of SARS-CoV-2 Related Disease (COVID-19). Front Immunol. 
2020;11:1451. Published 2020 Jun 19. doi:10.3389/fimmu.2020.01451 
4. Torjesen I. Covid-19: Public health agencies review whether vitamin D 
supplements could reduce risk. BMJ. 2020;369:m2475. Published 2020 Jun 19. 
doi:10.1136/bmj.m2475 
5. Hribar CA, Cobbold PH, Church FC. Potential Role of Vitamin D in the Elderly to 
Resist COVID-19 and to Slow Progression of Parkinson's Disease. Brain Sci. 
2020;10(5):284. Published 2020 May 8. doi:10.3390/brainsci10050284 
6. NIH Workshop on Post-Acute Sequelae of COVID-19. Accessed 25 Jan 2021. 
Available at:  https://www.niaid.nih.gov/news-events/workshop-post-acute-
sequelae-covid-19   
7. Mayo Clinic: COVID-19 (coronavirus): Long-term Effects. Accessed 8 Jan 2021 
from https://www.mayoclinic.org/diseases-conditions/coronavirus/in-
depth/coronavirus-long-term-effects/art-20490351 
8. Jacobs LG, Gourna Paleoudis E, Lesky-Di Bari D, et al. Persistence of symptoms 
and quality of life at 35 days after hospitalization for COVID-19 infection. PLoS 
One. 2020;15(12):e0243882. Published 2020 Dec 11. 
doi:10.1371/journal.pone.0243882 
9. Halpin SJ, McIvor C, Whyatt G, Adams A, Harvey O, McLean L, Walshaw C, 
Kemp S, Corrado J, Singh R, Collins T, O'Connor RJ, Sivan M. Postdischarge 
symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-
sectional evaluation. J Med Virol. 2021 Feb;93(2):1013-1022. doi: 
10.1002/jmv.26368. Epub 2020 Aug 17. PMID: 32729939. 
10. Garrigues E, Janvier P, Kherabi Y, et al. Post-discharge persistent symptoms 
and health-related quality of life after hospitalization for COVID-19. J Infect. 
2020;81(6):e4-e6. doi:10.1016/j.jinf.2020.08.029 
11. CDC Morbidity and Mortality Weekly Report: Symptom Duration and Risk Factors 
for Delayed Return to Usual Health Among Outpatients with Covid-19 in a 
Multistate Health Care Systems Network – United States - March-June 2020. 
Accessed on 25 Jan 2021 from 
https://www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htm  
12. Couzin-Frankel, J. From ‘brain fog’ to heart damage, COVID-19’s lingering 
problems alarm scientists. July 31, 2020. Accessed 25 January 2021 
from https://www.sciencemag.org/news/2020/07/brain-fog-heart-damage-covid-
19-s-lingering-problems-alarm-scientists  
13. Cooney, Elizabeth. Stat / Health Column: Long after the fire of a covid-19 
infection, mental and neurological effects can still smolder. Accessed 26 Jan 


29 
 
2021 from https://www.statnews.com/2020/08/12/after-covid19-mental-
neurological-effects-smolder/  
14. Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of Cardiovascular Magnetic 
Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 
2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265–1273. 
doi:10.1001/jamacardio.2020.3557 
15. Carfì A, Bernabei R, Landi F, for the Gemelli Against COVID-19 Post-Acute Care 
Study Group. Persistent Symptoms in Patients After Acute COVID-
19. JAMA. 2020;324(6):603–605. doi:10.1001/jama.2020.12603 
16. Gemelli Against COVID-19 Post-Acute Care Study Group. Post-COVID-19 global 
health strategies: the need for an interdisciplinary approach. Aging Clin Exp Res. 
2020 Aug;32(8):1613-1620. doi: 10.1007/s40520-020-01616-x. Epub 2020 Jun 
11. PMID: 32529595; PMCID: PMC7287410. 
17. Scaioli E, Liverani E, Belluzzi A. The Imbalance between n-6/n-3 
Polyunsaturated Fatty Acids and Inflammatory Bowel Disease: A Comprehensive 
Review and Future Therapeutic Perspectives. Int. J. Mol. Sci. 2017; 18(12): 
e2619 
18. Yaqoob, P. Mechanisms underlying the immunomodulatory effects of n-3 PUFA. 
Proc. Nutr. Soc. 2010; 69(3): 311–315 
19. Rees D, Miles EA, Banerjee T, Wells SJ, Roynette CE, Wahle KW, Calder PC. 
Dose-related effects of eicosapentaenoic acid on innate immune function in 
healthy humans: A comparison of young and older men. Am. J. Clin. Nutr. 2006; 
83: 331–342 
20. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, 
Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaefer EJ, Wolff SM, 
Dinarello CA. The effect of dietary supplementation with n-3 polyunsaturated fatty 
acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear 
cells. N. Engl. J. Med. 1989; 320: 265–271 
21. Kelei Li, Tao Huang, Jusheng Zheng, Duo Li. Effect of Marine-Derived n-3 
Polyunsaturated Fatty Acids on C-Reactive Protein, Interleukin 6 and Tumor 
Necrosis Factor a: A Meta-Analysis. PLOS ONE, 2014;9(2): e88103 
22. Mogensen TH, Melchjorsen J, Hollsberg P, Paludan SR. Activation of NF-kappa 
B in virus-infected macrophages is dependent on mitochondrial oxidative stress 
and intracellular calcium: Downstream involvement of the kinases TGF-beta-
activated kinase 1, mitogen-activated kinase/extracellular signal-regulated kinase 
kinase 1, and I kappa B kinase. J Immunol. 2003; 170(12): 6224– 6233 
23. Beyazit Y, Purnak T, Kekilli M. Role of nitric oxide in the treatment of non-
alcoholic fatty liver by omega-3 fatty acids. Aliment. Pharmacol. Ther. 2010; 
32(2): 303–304 
24. Adli M, Merkhofer E, Cogswell P, Baldwin AS. IKKalpha and IKKbeta each 
function to regulate NFkappaB activation in the TNF-induced/canonical pathway. 
PLoS One. 2010 Feb 25; 5(2): e9428 
25. Sabater J, Masclans JR, Sacanell J, Chacon P, Sabin P, Plnas M. Effects of an 
omega-3 fatty acid enriched lipid emulsion on eicosanoid synthesis in acute 
respiratory distress syndrome (ARDS): A prospective, randomized, double-blind, 
parallel group study Nutr Metab (Lond). 2011; 8(1): 22. 


30 
 
26. Dushianthan A, Rebecca Cusack V, Burgess A, Grocott M, Calder P. 
Immunonutrition for Adults With ARDS: Results From a Cochrane Systematic 
Review and Meta-Analysis, Respiratory Care January 2020; 65(1): 99-110 
27. Langlois P, D'Aragon F, Hardy G, Manzanares W. Omega-3 polyunsaturated 
fatty acids in critically ill patients with acute respiratory distress syndrome: A 
systematic review and meta-analysis. Nutrition. 2019; 61: 84-92 
28. Chen H, Wang S, Zhao Y, Luo Y, Tong H, Su L. Correlation analysis of omega-3 
fatty acids and mortality of sepsis and sepsis-induced ARDS in adults: data from 
previous randomized controlled trials. Nutr J. 2018; 17(1): 57 
29. NBC News, NJ Gov. Murphy says state is hardest hit by coronavirus in U.S. May 
12, 2020. Accessed at: https://www.nbcnews.com/video/new-jersey-gov-murphy-
says-state-is-hardest-hit-by-coronavirus-in-u-s-83346501863 
30. NJ Department of Health / Covid-19 Dashboard. Accessed 8 Jan 2021 from 
https://covid19.nj.gov/ 
31. Barrett, E.S., Horton, D.B., Roy, J. et al. Prevalence of SARS-CoV-2 infection in 
previously undiagnosed health care workers in New Jersey, at the onset of the 
U.S. COVID-19 pandemic. BMC Infect Dis 20, 853 (2020). 
https://doi.org/10.1186/s12879-020-05587-2 
32. Gooch, Kelly. Becker’s Hospital Review: Covid-19 Sidelines over 100 New 
Jersey Hospital Workers. Dec 2, 2020. Accessed on 27 Jan 2021 from 
https://www.beckershospitalreview.com/workforce/covid-19-sidelines-over-100-
new-jersey-hospital-workers.html.  
33. American Heart Association: Professional Heart Daily (13 March 2017. Omega-3 
Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of 
Clinical Cardiovascular Disease. Available at: 
https://professional.heart.org/en/science-news/omega-3-polyunsaturated-fatty-
acid-fish-oil-supplementation-and-the-prevention  
34. Scientific Opinion on the Tolerable Upper Intake Level of eicosapentaenoic acid 
(EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). (Source: 
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) / 27 July 2012 
https://doi.org/10.2903/j.efsa.2012.2815|) 
35. U.S. Food and Drug Administration. Summary of qualified health claims subject 
to enforcement discretion.  2014. Available at: https://www.fda.gov/food/food-
labeling-nutrition/qualified-health-claims-letters-enforcement-discretion  
36. Insights From the OPERA Randomized Trial--Emmanuel Akintoye , Prince Sethi, 
William S. Harris , Paul A. Thompson , Roberto Marchioli , Luigi Tavazzi , 
Roberto Latini , Mias Pretorius , Nancy J. Brown , Peter Libby, Dariush 
Mozaffarian, Originally published5 Nov 
2018https://doi.org/10.1161/CIRCOUTCOMES.118.004584Circulation: 
Cardiovascular Quality and Outcomes. 2018;11 
37. n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: 
clinical observations and mechanistic insights: John K Wachira, Mark K Larson, 
William S Harris;   PMID:  24472372, DOI:  10.1017/S000711451300425X    
38. Elevated plasma glucose and lowered triglyceride levels from omega-3 fatty acid 
supplementation in type II diabetes ; K E Friday  , M T Childs, C H Tsunehara, W 


31 
 
Y Fujimoto, E L Bierman, J W Ensinck--Diabetes Care . 1989 Apr; 12(4):276-81.  
doi:10.2337/diacare.12.4.276.   
39. Effects of Omega-3 Fatty Acid Supplementation on Glucose Control and Lipid 
Levels in Type 2 Diabetes: A Meta-Analysis, Cai Chen, 1 , 2  Xuefeng Yu, 1  and 
Shiying Shao 1 ,* Published online 2015 Oct 2.  doi: 
10.1371/journal.pone.0139565 
40. Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-
analysis of controlled trials. Circulation. 1993;88(2):523-533. 
doi:10.1161/01.cir.88.2.523 
41. Cleveland Heart Lab: Omega-3 Fatty Acids: A Natural Way to Lower Blood 
Pressure. Blog post 20 August 2015. Available at: 
https://www.clevelandheartlab.com/blog/horizons-omega-3-fatty-acids-a-natural-
way-to-lower-blood-pressure/ 
42. Overview of Omega-3 Fatty Acid Therapies; J. Chris Bradberry, PharmD and 
Daniel E. Hilleman, PharmD----PMID: 24391388         
43. Link, R. Healthline blog: 8 Little-Known Side Effects of Too Much Fish Oil. 17 
July 2018. Available at: https://www.healthline.com/nutrition/fish-oil-side-
effects#section4 
44. Khodarahmi M, Azadbakht L. Dietary fat intake and functional dyspepsia. Adv 
Biomed Res. 2016;5:76. Published 2016 Apr 21. doi:10.4103/2277-9175.180988 
 
 
 
 
 
 
 
 
 
 


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Appendix A: Inclusion / Exclusion Eligibility Survey 
 
 
 
 
 
 
 
 
 
 


33 
 
 


34 
 
 


35 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix B: Demographic/Baseline Survey 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


36 
 
 


37 
 
 


38 
 
 
 
 
 
 
 
Appendix C: Bi-weekly Symptoms & Quality of Life Post Covid Survey 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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40 
 
 
 


41 
 
 
 
 


42 
 
 
 
Appendix D: Follow-up Feasibility Survey &  
Study Discontinuation Verification 
 
 
 
 
 
 
 
 
 
 
 


43 
 
 


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46 
 
 
 
 
 
Appendix E: Omega-3 Supplement & Labeling Information 
 
 
 
 
 
 
 
 


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48 
 
 
 
Labeling: There will be only ONE label for both the placebo and IP, to keep the blind. 
 
Investigational drug / Placebo label (below is the minimum that will be included)   
● Subject ID# 
● Expiration date (as per sponsor) 
● prescription (serial) number. 
● date of each dispensing. 
● subject's name. 
● directions for use. 
● name and strength of the drug product (or active ingredient(s) in a 
compounded prescription)  --------> inv. IP name / Placebo  
● prescriber's name. 
● Initials of dispensing pharmacist. 
Keep at Room Temperature between 59-86 ᵒF  
Caution: New Drug Limited by Federal (or U.S.) law to Investigational Use. 
 
 
 
 
 


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