NCT04658433

The Effect of Omega -3 Supplements on the Serum Levels of ACE/ACE2 Ratio as a Potential Key in Cardiovascular Disease and COVID-19; A Randomized Clinical Trial in the Covid-19 Uninfected Jordanian People

Completed NA Last updated 24 February 2022

What this trial tests

NA trial testing 300 mg of omega3-FA in Cardiovascular Risk Factor in 100 participants. Completed in 10 February 2022.

Timeline

5 March 2021

Primary endpoint
20 December 2021

10 February 2022

Quick facts

Lead sponsor	Applied Science Private University
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	prevention
Enrollment	100
Start date	5 March 2021
Primary completion	20 December 2021
Estimated completion	10 February 2022
Sites	1 location across Jordan

Drugs / interventions tested

• 300 mg of omega3-FA

Conditions studied

• Cardiovascular Risk Factor — all drugs for Cardiovascular Risk Factor →
• Covid19 — all drugs for Covid19 →

Sponsor

Applied Science Private University

Who can join

Adults 35 to 65, any sex, with Cardiovascular Risk Factor or Covid19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The Renin-Angiotensin-Aldosterone System (RAAS) is involved in blood pressure regulation and electrolyte balance. Angiotensin-converting enzyme (ACE) is a critical regulator of RAAS by cleaving angiotensin (Ang1) to Angiotensin2 (Ang2), which is the most powerful biologically active product of RAAS \[1\]. In the same context, angiotensin-converting enzyme 2 (ACE2) converts Ang2 to Ang (1-7), which is a vasodilator, antithrombotic, and antihypertrophic peptide \[2\]. ACE2 which is found in many tissues \[3\] has opposite effects to ACE on the heart, kidneys, and lungs \[4\]. Many pathological conditions, in particular cardiovascular disease (CVD), have shown a link between a disturbance in ACE/ACE2 ratio and the downregulation of ACE2 levels \[5\]. Also, ACE/ACE2 has been reported to be higher in moderate to severe chronic heart failure \[6\] as well as systolic blood pressure \[7\]. Recently, an elevated ACE/ACE2 ratio is linked to Coronavirus disease 2019 (COVID-19). SARS-COV2 enters target cells by binding of the spike protein to ACE2 and a specific transmembrane serine protease 2 (TMPRSS2) for the spike (S) protein priming, which also leads to downregulation of ACE2 \[8\]. Down-regulation of ACE2 caused by Coronavirus may have a potential role in the pathogenesis of COVID-19 infection. Accordingly, people with a higher ACE/ACE2 ratio may be more at increased risk of worse Covid-19 consequences \[9\].

On the other hand, omega-3 fatty acids could decrease CVD risk by their anti-inflammatory anti-thrombotic function \[10\]. A meta-analysis comprising 15,806 patients, showed that omega-3 fatty acids associated with a 30% reduction in fatal myocardial infarction and sudden death, in addition to a 20% reduction in overall mortality \[11\]. To the best of our knowledge, no clinical trials have evaluated the effect of omega-3 supplementation on serum ACE/ACE2 ratio which is recently ascribed as a potential key in 2019 Covid-19 as well as CVD \[5,9\].

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Dissecting lipid metabolism alterations in SARS-CoV-2.
   Casari I, Manfredi M, Metharom P, Falasca M. · · 2021 · cited 90× · PMID 33571544 · DOI 10.1016/j.plipres.2021.101092
2. The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.
   Ning Q, Wu D, Wang X, Xi D, et al · · 2022 · cited 64× · PMID 35197452 · DOI 10.1038/s41392-022-00907-1
3. The roles of lipids in SARS-CoV-2 viral replication and the host immune response.
   Theken KN, Tang SY, Sengupta S, FitzGerald GA. · · 2021 · cited 59× · PMID 34599996 · DOI 10.1016/j.jlr.2021.100129
4. Micronutrients, Phytochemicals and Mediterranean Diet: A Potential Protective Role against COVID-19 through Modulation of PAF Actions and Metabolism.
   Detopoulou P, Demopoulos CA, Antonopoulou S. · · 2021 · cited 52× · PMID 33573169 · DOI 10.3390/nu13020462
5. Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review.
   Talasaz AH, Sadeghipour P, Aghakouchakzadeh M, Dreyfus I, et al · · 2021 · cited 43× · PMID 34649702 · DOI 10.1016/j.jacc.2021.08.021
6. The Role of High-Density Lipoprotein in COVID-19.
   Wang G, Deng J, Li J, Wu C, et al · · 2021 · cited 19× · PMID 34335279 · DOI 10.3389/fphar.2021.720283
7. COVID-19-associated hypertriglyceridemia and impact of treatment.
   Kaddoura R, Mohamed Ibrahim MI, Al-Amri M, Prabhakaran Nair A, et al · · 2024 · cited 2× · PMID 38449886 · DOI 10.3389/fmed.2024.1326156
8. The effect of omega-3 supplements on the serum levels of ACE/ACE2 ratio as a potential key in cardiovascular disease: A randomized clinical trial in participants with vitamin D deficiency.
   Daboul SM, Abusamak M, Mohammad BA, Alsayed AR, et al · · 2023 · cited 1× · PMID 37090459 · DOI 10.18549/pharmpract.2023.1.2761