Renin-Angiotensin SystemNCT05418361
The Effect of RAAS Blockers on ACE2 Levels
An observational study of Renin-Angiotensin System, run by Ain Shams University at 1 site in Egypt.
Trial summary
Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of drugs for treatment of hypertension, heart failure and chronic kidney disease However, the interplay between RAAS blockers and ACE2… Read more about this study
- Who is it for?
- Ages 43 to 67 yearsHealthy volunteers can take part
- Conditions the study is for
- Renin-Angiotensin System
- What is being tested?
- ACE inhibitor ,angiotensin receptor blockers
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Jun 2021to 20 Feb 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 43 to 67 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: patients with controlled Hypertension or heart failure presenting to Cardiac Rehabilitation Units taking ACE inhibitors or AGII blockers
Who may be able to join
- Patients age> 18 years
- Taking ACE II inhibitors or angiotensin II blockers (according to maximum tolerated dose specified by guidelines)
- History of essential hypertension or heart failure
Who cannot join
- patients who suffer from secondary hypertension, including idiopathic hyperaldosteronism, renal artery stenosis
- Patient reported history of severe liver disease
- a history or suspicion of alcohol or drug abuse; and mental illness
- Pregnant and breast feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Construction of an Evidence Based Startegy for the Use of Renin Angiotensin Aldosterone System Blockers for Future Targeting of ACE2 in Treatment of COVID19
Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of drugs for treatment of hypertension, heart failure and chronic kidney disease However, the interplay between RAAS blockers and ACE2 hasn't been fully elucidated SARS-CoV-2 is thought to infect host cells through ACE2 to cause coronavirus disease 2019 (COVID-19). Recent studies revealed that the spikes of COVID-19 could bind to the surface receptors of sensitive cells after contacting the airway surface, which may mediate virus entry into target cells and viral replication, and ACE2 might be a mediator of infection (South, Brady et al. 2020). Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were reported linking the use of RAAS blockers and the susceptibility to the virus. However, others showed that treatment with an RAAS blockers may downregulate the expression of ACE2 but have no significant effect on its activity This research importantly aimed to solve this important issue by determining the exact association between ARBs and ACE inhibitor and ACE2 activity and levels on clinical and experimental prospects.
Read the detailed description
Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of drugs for treatment of hypertension, heart failure and chronic kidney disease . The classic RAAS primarily involves 2 enzymes: renin, which cleaves angiotensinogen to the inactive decapeptide angiotensin (Ang) I; and ACE that hydrolyzes Ang I to the octapeptide Ang II, the well-known vasopressor agent . In fact, the enzymatic cascade of the RAS encompasses an ACE homolog known as ACE2. Whereas, the ACE2-dependent pathways directly yield Ang (1-9) from Ang I and degrade Ang II to Ang (1-7), which is vasodilator and acts as a feedback mechanism to antagonize the vasopressor effect of Ang II. Indeed, ACE inhibitors effectively attenuate Ang II formation and augment the levels of the heptapeptide Ang (1-7) . However, the interplay between RAAS blockers and ACE2 hasn't been fully elucidated.
SARS-CoV-2 is thought to infect host cells through ACE2 to cause coronavirus disease 2019 (COVID-19). Recent studies revealed that the spikes of COVID-19 could bind to the surface receptors of sensitive cells after contacting the airway surface, which may mediate virus entry into target cells and viral replication, and ACE2 might be a mediator of infection Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were reported linking the use of RAAS blockers and the susceptibility to the virus. However, others showed that treatment with an RAAS blockers may downregulate the expression of ACE2 but have no significant effect on its activity .
Furthermore, SARS-CoV-2 infection has largely been influenced by multiorgan involvement inducing multiple comorbidities due to the wide distribution of ACE2 thought out the whole body. In addition, hypertension, cardiovascular disease, and chronic kidney disease are supposed to be potential but unconfirmed risk factors for COVID-19 in adults and children . However, the expression of ACE2 may be lower in patients with hypertension than in people with normal blood pressure . Concluding more conflicting evidences for the association of COVID-19 with RAAS inhibitors.
Given the RAAS importance to cardiovascular and kidney physiology, and the association between chronic diseases and COVID-19, could shed light on potential relationships between ACE inhibitor and ARB use and COVID-19.
Accordingly, evidences are required to solve the question of whether ARBs and ACE inhibitor have either favorable or harmful effects on the susceptibility to SARS-CoV-2 in addition to the severity and outcomes of COVID-19 infection. This research importantly aimed to solve this important issue by determining the exact association between ARBs and ACE inhibitor and ACE2 activity and levels on clinical and experimental prospects.
- Conditions
- Renin-Angiotensin System
- Being tested
- ACE inhibitor ,angiotensin receptor blockers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACE inhibitor ,angiotensin receptor blockersDrug
patients taking ACEI or ARBs with cardiovascular disease
| Study group | Role | What they receive |
|---|---|---|
| ACEIs group | Patients suffer from cardiovascular diseases)controlled hypertension or heart failure ) taking ACE inhibitors Receives: Drug: ACE inhibitor ,angiotensin receptor blockers | |
| ARBs group | Patients suffer from cardiovascular diseases)controlled hypertension or heart failure ) taking Angiotensin receptor blockers Receives: Drug: ACE inhibitor ,angiotensin receptor blockers | |
| healthy | matched healthy controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of RAAS blockers on ACE2 levels
ACE2 levels in cardiovascular disease patients
Measured: at least 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2022
- Study start15 Jun 2021
- Primary completion20 Feb 2022
- Study completion20 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renin-Angiotensin SystemStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- ebtehal el demerdash, prof, Principal investigator, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05418361
- Sponsor's protocol ID
- FAMASU/2021
- Status last verified
- Jun 2022
- First submitted
- 10 Jun 2022
- Last updated
- 15 May 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Farid Fahmy S, El Derany MO, Khorshid H, Saleh A, El-Demerdash E. Effect of renin angiotensin blockers on angiotensin converting enzyme 2 level in cardiovascular patients. BMC Pharmacol Toxicol. 2023 Apr 14;24(1):24. doi: 10.1186/s40360-023-00667-w.
PubMed 37060024
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Construction of an Evidence Based Startegy for the Use of Renin Angiotensin Aldosterone System Blockers for Future Targeting of ACE2 in Treatment of COVID19
- ClinicalTrials.gov ID
- NCT05418361
- Acronym / sponsor ID
- FAMASU/2021
- Conditions
- Renin-Angiotensin System
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 15 Jun 2021 (actual)
- Primary completion
- 20 Feb 2022 (actual)
- Study completion
- 20 Feb 2022 (actual)
- First posted
- 14 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of drugs for treatment of hypertension, heart failure and chronic kidney disease However, the interplay between RAAS blockers and ACE2 hasn't been fully elucidated SARS-CoV-2 is thought to infect host cells through ACE2 to cause coronavirus disease 2019 (COVID-19). Recent studies revealed that the spikes of COVID-19 could bind to the surface receptors of sensitive cells after contacting the airway surface, which may mediate virus entry into target cells and viral replication, and ACE2 might be a mediator of infection (South, Brady et al. 2020). Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were reported linking the use of RAAS blockers and the susceptibility to the virus. However, others showed that treatment with an RAAS blockers may downregulate the expression of ACE2 but have no significant effect on its activity This research importantly aimed to solve this important issue by determining the exact association between ARBs and ACE inhibitor and ACE2 activity and levels on clinical and experimental prospects.
Detailed description
Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of drugs for treatment of hypertension, heart failure and chronic kidney disease . The classic RAAS primarily involves 2 enzymes: renin, which cleaves angiotensinogen to the inactive decapeptide angiotensin (Ang) I; and ACE that hydrolyzes Ang I to the octapeptide Ang II, the well-known vasopressor agent . In fact, the enzymatic cascade of the RAS encompasses an ACE homolog known as ACE2. Whereas, the ACE2-dependent pathways directly yield Ang (1-9) from Ang I and degrade Ang II to Ang (1-7), which is vasodilator and acts as a feedback mechanism to antagonize the vasopressor effect of Ang II. Indeed, ACE inhibitors effectively attenuate Ang II formation and augment the levels of the heptapeptide Ang (1-7) . However, the interplay between RAAS blockers and ACE2 hasn't been fully elucidated.
SARS-CoV-2 is thought to infect host cells through ACE2 to cause coronavirus disease 2019 (COVID-19). Recent studies revealed that the spikes of COVID-19 could bind to the surface receptors of sensitive cells after contacting the airway surface, which may mediate virus entry into target cells and viral replication, and ACE2 might be a mediator of infection Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were reported linking the use of RAAS blockers and the susceptibility to the virus. However, others showed that treatment with an RAAS blockers may downregulate the expression of ACE2 but have no significant effect on its activity .
Furthermore, SARS-CoV-2 infection has largely been influenced by multiorgan involvement inducing multiple comorbidities due to the wide distribution of ACE2 thought out the whole body. In addition, hypertension, cardiovascular disease, and chronic kidney disease are supposed to be potential but unconfirmed risk factors for COVID-19 in adults and children . However, the expression of ACE2 may be lower in patients with hypertension than in people with normal blood pressure . Concluding more conflicting evidences for the association of COVID-19 with RAAS inhibitors.
Given the RAAS importance to cardiovascular and kidney physiology, and the association between chronic diseases and COVID-19, could shed light on potential relationships between ACE inhibitor and ARB use and COVID-19.
Accordingly, evidences are required to solve the question of whether ARBs and ACE inhibitor have either favorable or harmful effects on the susceptibility to SARS-CoV-2 in addition to the severity and outcomes of COVID-19 infection. This research importantly aimed to solve this important issue by determining the exact association between ARBs and ACE inhibitor and ACE2 activity and levels on clinical and experimental prospects.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ACEIs group | – | Drug: ACE inhibitor ,angiotensin receptor blockersPatients suffer from cardiovascular diseases)controlled hypertension or heart failure ) taking ACE inhibitors |
| ARBs group | – | Drug: ACE inhibitor ,angiotensin receptor blockersPatients suffer from cardiovascular diseases)controlled hypertension or heart failure ) taking Angiotensin receptor blockers |
| healthy | – | –matched healthy controls |
Who may qualify
- Ages
- 43 to 67 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- patients with controlled Hypertension or heart failure presenting to Cardiac Rehabilitation Units taking ACE inhibitors or AGII blockers
Key inclusion criteria (3 listed)
- Patients age> 18 years
- Taking ACE II inhibitors or angiotensin II blockers (according to maximum tolerated dose specified by guidelines)
- History of essential hypertension or heart failure
Key exclusion criteria (4 listed)
- patients who suffer from secondary hypertension, including idiopathic hyperaldosteronism, renal artery stenosis
- Patient reported history of severe liver disease
- a history or suspicion of alcohol or drug abuse; and mental illness
- Pregnant and breast feeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACE inhibitor ,angiotensin receptor blockerspatients taking ACEI or ARBs with cardiovascular disease | Drug | ACEIs group, ARBs group |
Primary outcome
Effect of RAAS blockers on ACE2 levels
Time frame: at least 6 months
ACE2 levels in cardiovascular disease patients
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2023.
- Derived from this study: PubMed 37060024Farid Fahmy S, El Derany MO, Khorshid H, Saleh A, El-Demerdash E. Effect of renin angiotensin blockers on angiotensin converting enzyme 2 level in cardiovascular patients. BMC Pharmacol Toxicol. 2023 Apr 14;24(1):24. doi: 10.1186/s40360-023-00667-w.
Related trials for Renin-Angiotensin System
RecruitingPhase 2
Effect of an Isolevuglandin Scavenger on Salt Sensitivity of Blood Pressure and Immune Cell Activation in Humans
Salt Sensitivity of Blood Pressure, High Blood Pressure
Enrolling by invitation
RAndomized EHR-based Prescribing to Improve Disease-modifying Therapies for Cardio-Kidney-Metabolic Care (RAPID-CKM)
Chronic Kidney Disease, Type 2 Diabetes
Enrolling by invitationPhase 4
Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)
Chronic Kidney Disease, Type 2 Diabetes
Not yet recruitingPhase 4
Mechanistic Assessment of Norepinephrine Therapy vs. Angiotensin-II in Septic Shock
Septic Shock
RecruitingPhase 4
A Prompt REstart Study of Renin-Angiotensin System Inhibitors After Acute Kidney Injury
Acute Kidney Injury
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ebtehal el demerdash, prof principal investigator
Ain Shams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Renin-Angiotensin System, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of RAAS blockers on ACE2 levels (time frame: at least 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05418361, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023.