HypertensionMRDLTNCT06622304
Exploring the Effects of Antihypertensive and Lipid-Lowering Drugs on Inflammatory Cytokine Levels
An observational study of Hypertension and Dyslipidemias, run by Guangzhou Institute of Respiratory Disease at 1 site in China.
Trial summary
This study investigates the causal relationships between antihypertensive and lipid-lowering drugs and inflammatory cytokines using a drug-targeted Mendelian randomization approach. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension, Dyslipidemias, Inflammatory Response
- How many people
- 250,736 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2024to 11 Sep 2024
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population includes adult patients diagnosed with hypertension, coronary artery disease, or dyslipidemia. These participants have genome-wide data collected through genome-wide association studies (GWAS) and include measurements of inflammatory cytokines. The study focuses on the effect of drug interventions on inflammatory biomarkers.
Who may be able to join
- Participants aged 18 years or older.
- Diagnosed with hypertension, coronary artery disease, or dyslipidemia.
- Availability of complete genome-wide data and inflammatory cytokine levels.
- Willingness to participate in the study and provide the required clinical data.
Who cannot join
- Participants under the age of 18.
- Individuals with severe chronic diseases or other conditions that may significantly influence inflammatory responses.
- Individuals unwilling or unable to provide necessary clinical or genomic data.
- Pregnant or breastfeeding women.
Trial locations and contacts
1 site in 1 country.
China1 site
Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120
About this study
Official title: Mendelian Randomization Analysis of Drug Targets: Exploring the Impact of Antihypertensive and Lipid-Lowering Therapies on Inflammatory Cytokines
This study investigates the causal relationships between antihypertensive and lipid-lowering drugs and inflammatory cytokines using a drug-targeted Mendelian randomization approach. By leveraging genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data, the study evaluates the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), HMG-CoA reductase inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors on key inflammatory cytokines such as IL-1β, TNF-α, CRP, and MCP-1. The findings aim to provide insights into the prevention and control of excessive inflammatory responses, particularly in patients with hypertension and dyslipidemia, by assessing the causal effects of these therapies.
Read the detailed description
This observational study focuses on elucidating the causal relationships between commonly prescribed antihypertensive drugs (ACEIs and ARBs) and lipid-lowering drugs (HMG-CoA reductase inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors) with various inflammatory cytokines, including IL-1β, TNF-α, CRP, MCP-1, and IFN-γ, using a drug-targeted Mendelian randomization (MR) framework. The study employs large-scale genetic data from European populations, drawing from genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) datasets, to construct instrumental variables that mimic the effects of drug exposure.
The primary aim is to explore how these pharmaceutical interventions influence inflammatory pathways at the molecular level. The use of MR methods enables causal inference by utilizing genetic variants within or near drug-target genes, allowing for the estimation of downstream effects similar to those produced by actual drug interventions. Key statistical methods, including inverse variance weighting and sensitivity analyses, are applied to ensure robustness and validity of the results.
This research provides critical evidence for the selection of antihypertensive and lipid-lowering therapies that not only manage cardiovascular risk factors but also modulate inflammation, contributing to personalized medicine strategies for patients with chronic inflammatory conditions. Furthermore, the findings have broader implications for drug repurposing and the development of new therapeutic targets aimed at mitigating inflammatory processes that underlie various chronic diseases.
- Conditions
- Hypertension, Dyslipidemias, Inflammatory Response, Chronic Inflammation, Inflammatory Cytokines
- Keywords
- Antihypertensive Drugs, Lipid-Lowering Drugs, Mendelian Randomization, ACE Inhibitors, ARBs, HMG-CoA Reductase Inhibitors, PCSK9 Inhibitors, NPC1L1 Inhibitors, IL-1β, TNF-α, CRP, MCP-1, Inflammatory Pathways, Genetic Association Studies, Causal Inference
- Medical subject headings
- Hypertension, Dyslipidemias
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in IL-1β Levels Due to ACE Inhibitors
The primary outcome is the reduction in plasma levels of IL-1β due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and IL-1β levels using Mendelian randomization.（Unit: pg/mL）
Measured: Baseline to 12 months
Reduction in TNF-α Levels Due to ACE Inhibitors
The primary outcome is the reduction in plasma levels of TNF-α due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and TNF-α levels using Mendelian randomization.（Unit: pg/mL）
Measured: Baseline to 12 months
Reduction in CRP Levels Due to ACE Inhibitors
The primary outcome is the reduction in plasma levels of CRP due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and CRP levels using Mendelian randomization.（Unit: mg/L）
Measured: Baseline to 12 months
Modulation of MCP-1 Levels Due to Statin Therapy
The primary outcome is the modulation of plasma levels of MCP-1 in patients treated with statins (HMG-CoA reductase inhibitors). The study investigates the effect of statins on MCP-1 levels.（Unit: pg/mL）
Measured: Baseline to 12 months
Modulation of MIP-1α Levels Due to Statin Therapy
The primary outcome is the modulation of plasma levels of MIP-1α in patients treated with statins (HMG-CoA reductase inhibitors).（Unit: pg/mL）
Measured: Baseline to 12 months
Modulation of MIP-1β Levels Due to Statin Therapy
The primary outcome is the modulation of plasma levels of MIP-1β in patients treated with statins (HMG-CoA reductase inhibitors).（Unit: pg/mL）
Measured: Baseline to 12 months
Reduction in IL-1β Levels Due to PCSK9 Inhibitors
The primary outcome is the reduction in plasma levels of IL-1β in individuals exposed to PCSK9 inhibitors.（Unit: pg/mL）
Measured: Baseline to 12 months
Reduction in IL-6 Levels Due to PCSK9 Inhibitors
The primary outcome is the reduction in plasma levels of IL-6 in individuals exposed to PCSK9 inhibitors.（Unit: pg/m）
Measured: Baseline to 12 months
Secondary outcomes (5)
Reduction in Cardiovascular Events Due to Antihypertensive Therapy
The secondary outcome evaluates the reduction in cardiovascular events (e.g., myocardial infarction, stroke) linked to antihypertensive therapies such as ACEIs and ARBs.
Measured: Baseline to 24 months
Changes in LDL-C Levels Due to Statin Therapy
This outcome examines changes in LDL cholesterol (LDL-C) levels due to statin therapy.
Measured: Baseline to 24 months
Changes in HDL-C Levels Due to Statin Therapy
This outcome examines changes in HDL cholesterol (HDL-C) levels due to statin therapy.
Measured: Baseline to 24 months
Reduction in IL-1β Levels Due to PCSK9 Inhibitors
The secondary outcome measures the reduction in IL-1β levels linked to PCSK9 inhibitors.
Measured: Baseline to 24 months
Changes in Cardiometabolic Outcomes Due to PCSK9 Inhibitors
This secondary outcome measures changes in cardiometabolic outcomes, including changes in lipid levels and inflammatory cytokine profiles.
Measured: Baseline to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2024
- Study start1 Apr 2024
- Primary completion1 Aug 2024
- Study completion11 Sep 2024
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 HypertensionStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 250,736 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guangzhou Institute of Respiratory Disease
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine
- Responsible party
- Principal investigator, Zhibin Xu, Guangzhou Institute of Respiratory Disease
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06622304
- Sponsor's protocol ID
- YYKC-2021-01-102
- Acronym
- MRDLT
- Status last verified
- Oct 2024
- First submitted
- 29 Sep 2024
- Last updated
- 3 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) including de-identified genome-wide association study (GWAS) data and inflammatory cytokine levels will be shared. The data will be made available to qualified researchers upon request, following appropriate approval.
Publications
Xin J, Xu Z, Zhang F, Sun Y, Wang X, Wu C, Zhao L. Mendelian randomization-based observational cohort study on drug targets: Impact of antihypertensive and lipid-lowering therapies on inflammatory cytokines. Medicine (Baltimore). 2025 Mar 7;104(10):e41771. doi: 10.1097/MD.0000000000041771.
PubMed 40068040
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mendelian Randomization Analysis of Drug Targets: Exploring the Impact of Antihypertensive and Lipid-Lowering Therapies on Inflammatory Cytokines
- ClinicalTrials.gov ID
- NCT06622304
- Acronym / sponsor ID
- MRDLT / YYKC-2021-01-102
- Conditions
- Hypertension, Dyslipidemias, Inflammatory Response, Chronic Inflammation, Inflammatory Cytokines
- Keywords
- Antihypertensive Drugs, Lipid-Lowering Drugs, Mendelian Randomization, ACE Inhibitors, ARBs, HMG-CoA Reductase Inhibitors, PCSK9 Inhibitors, NPC1L1 Inhibitors
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 250,736 participants (actual)
- Lead sponsor
- Guangzhou Institute of Respiratory DiseaseUniversity, hospital or other
- Collaborators
- Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 11 Sep 2024 (actual)
- First posted
- 2 Oct 2024 (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.
This study investigates the causal relationships between antihypertensive and lipid-lowering drugs and inflammatory cytokines using a drug-targeted Mendelian randomization approach. By leveraging genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data, the study evaluates the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), HMG-CoA reductase inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors on key inflammatory cytokines such as IL-1β, TNF-α, CRP, and MCP-1. The findings aim to provide insights into the prevention and control of excessive inflammatory responses, particularly in patients with hypertension and dyslipidemia, by assessing the causal effects of these therapies.
Detailed description
This observational study focuses on elucidating the causal relationships between commonly prescribed antihypertensive drugs (ACEIs and ARBs) and lipid-lowering drugs (HMG-CoA reductase inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors) with various inflammatory cytokines, including IL-1β, TNF-α, CRP, MCP-1, and IFN-γ, using a drug-targeted Mendelian randomization (MR) framework. The study employs large-scale genetic data from European populations, drawing from genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) datasets, to construct instrumental variables that mimic the effects of drug exposure.
The primary aim is to explore how these pharmaceutical interventions influence inflammatory pathways at the molecular level. The use of MR methods enables causal inference by utilizing genetic variants within or near drug-target genes, allowing for the estimation of downstream effects similar to those produced by actual drug interventions. Key statistical methods, including inverse variance weighting and sensitivity analyses, are applied to ensure robustness and validity of the results.
This research provides critical evidence for the selection of antihypertensive and lipid-lowering therapies that not only manage cardiovascular risk factors but also modulate inflammation, contributing to personalized medicine strategies for patients with chronic inflammatory conditions. Furthermore, the findings have broader implications for drug repurposing and the development of new therapeutic targets aimed at mitigating inflammatory processes that underlie various chronic diseases.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population includes adult patients diagnosed with hypertension, coronary artery disease, or dyslipidemia. These participants have genome-wide data collected through genome-wide association studies (GWAS) and include measurements of inflammatory cytokines. The study focuses on the effect of drug interventions on inflammatory biomarkers.
Key inclusion criteria (4 listed)
- Participants aged 18 years or older.
- Diagnosed with hypertension, coronary artery disease, or dyslipidemia.
- Availability of complete genome-wide data and inflammatory cytokine levels.
- Willingness to participate in the study and provide the required clinical data.
Key exclusion criteria (4 listed)
- Participants under the age of 18.
- Individuals with severe chronic diseases or other conditions that may significantly influence inflammatory responses.
- Individuals unwilling or unable to provide necessary clinical or genomic data.
- Pregnant or breastfeeding women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Reduction in IL-1β Levels Due to ACE Inhibitors
Time frame: Baseline to 12 months
The primary outcome is the reduction in plasma levels of IL-1β due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and IL-1β levels using Mendelian randomization.（Unit: pg/mL）
Reduction in TNF-α Levels Due to ACE Inhibitors
Time frame: Baseline to 12 months
The primary outcome is the reduction in plasma levels of TNF-α due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and TNF-α levels using Mendelian randomization.（Unit: pg/mL）
Reduction in CRP Levels Due to ACE Inhibitors
Time frame: Baseline to 12 months
The primary outcome is the reduction in plasma levels of CRP due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and CRP levels using Mendelian randomization.（Unit: mg/L）
Modulation of MCP-1 Levels Due to Statin Therapy
Time frame: Baseline to 12 months
The primary outcome is the modulation of plasma levels of MCP-1 in patients treated with statins (HMG-CoA reductase inhibitors). The study investigates the effect of statins on MCP-1 levels.（Unit: pg/mL）
Modulation of MIP-1α Levels Due to Statin Therapy
Time frame: Baseline to 12 months
The primary outcome is the modulation of plasma levels of MIP-1α in patients treated with statins (HMG-CoA reductase inhibitors).（Unit: pg/mL）
Modulation of MIP-1β Levels Due to Statin Therapy
Time frame: Baseline to 12 months
The primary outcome is the modulation of plasma levels of MIP-1β in patients treated with statins (HMG-CoA reductase inhibitors).（Unit: pg/mL）
Reduction in IL-1β Levels Due to PCSK9 Inhibitors
Time frame: Baseline to 12 months
The primary outcome is the reduction in plasma levels of IL-1β in individuals exposed to PCSK9 inhibitors.（Unit: pg/mL）
Reduction in IL-6 Levels Due to PCSK9 Inhibitors
Time frame: Baseline to 12 months
The primary outcome is the reduction in plasma levels of IL-6 in individuals exposed to PCSK9 inhibitors.（Unit: pg/m）
5 secondary outcomes
Reduction in Cardiovascular Events Due to Antihypertensive Therapy
Time frame: Baseline to 24 months
Changes in LDL-C Levels Due to Statin Therapy
Time frame: Baseline to 24 months
Changes in HDL-C Levels Due to Statin Therapy
Time frame: Baseline to 24 months
Reduction in IL-1β Levels Due to PCSK9 Inhibitors
Time frame: Baseline to 24 months
Changes in Cardiometabolic Outcomes Due to PCSK9 Inhibitors
Time frame: Baseline to 24 months
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 3 Oct 2024.
- Derived from this study: PubMed 40068040Xin J, Xu Z, Zhang F, Sun Y, Wang X, Wu C, Zhao L. Mendelian randomization-based observational cohort study on drug targets: Impact of antihypertensive and lipid-lowering therapies on inflammatory cytokines. Medicine (Baltimore). 2025 Mar 7;104(10):e41771. doi: 10.1097/MD.0000000000041771.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) including de-identified genome-wide association study (GWAS) data and inflammatory cytokine levels will be shared. The data will be made available to qualified researchers upon request, following appropriate approval.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Hypertension and Dyslipidemias, run by Guangzhou Institute of Respiratory Disease at 1 site in China.
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 4 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 3 Oct 2024. 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 China. 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?
Reduction in IL-1β Levels Due to ACE Inhibitors (time frame: Baseline to 12 months). The study lists 8 primary outcomes in all. 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 NCT06622304, 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 3 Oct 2024.