ClinicalTrials.gov
ClinicalTrials.gov Menu

The Microbiome as a Target for Precision Medicine in Atherosclerosis (MIGATER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03434483
Recruitment Status : Recruiting
First Posted : February 15, 2018
Last Update Posted : August 22, 2018
Sponsor:
Collaborator:
Fundación para la Investigación Biomédica del Hospital Gregorio Maranon
Information provided by (Responsible Party):
Javier Bermejo Thomas, Hospital General Universitario Gregorio Marañon

Brief Summary:
Cardiovascular diseases are the main cause of death in industrialized countries. Among them, atherosclerosis has the highest prevalence and constitutes a common pathological pathway responsible for the majority of cases of chronic ischemic heart disease, acute myocardial infarction, heart failure and cerebrovascular disease. Classic studies have confirmed well-established etiopathogenic factors of atherosclerosis based on genetic and immunological components and environmental modifying agents such as diet and exercise. But in addition, recent experimental studies have shown that dysbiosis (alteration of the microbiota) may be an additional factor that participates in the onset and progression of atherosclerosis. The objective of this study is to identify the potential interactions between changes in the microbiota, changes in the immune status, the clinical evolution and the instability and progression of atherosclerosis.

Condition or disease Intervention/treatment
Acute Coronary Syndrome Atherosclerosis Procedure: Assessment of the atherosclerotic plaque in a moderate lession. Genetic: Gene variants in atherosclerosis Other: Microbiota analysis Other: Immunological analysis Other: Clinical evaluation

Detailed Description:

The study will prospectively study two groups of patients : 1) patients with acute coronary syndrome and 2) age and sex matched patients with chronic stable documented atherosclerosis.

Immune cell populations and immune-related metabolites will be characterized, the genetic profile of the main known functional variants will be determined, and the oral, gastrointestinal, and blood microbiota will be compared in both groups in a transversal observational design.

In addition, 1-year clinical follow-up will be performed and correlation with the evolution of the microbiota and immune response in a longitudinal design will be conducted.

Besides, an angiographic substudy, for those patients included in the study but that require revascularization of culprit artery according to clinical indication, will be 1 year follow-up and functional assessment and intravascular imaging and the degree of remodelling of the atherosclerotic plaque will be correlated with the evolution of the microbiota and immune response in a longitudinal design.


Study Type : Observational [Patient Registry]
Estimated Enrollment : 120 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 12 Months
Official Title: Microbiome, Inflammation and Genetics as a Target for Precision Medicine in AThERosclerosis
Actual Study Start Date : February 25, 2018
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Atherosclerosis

Group/Cohort Intervention/treatment
Acute Coronary Syndrome
Patients with an episode of acute coronary syndrome. Clinical evaluation 1 year. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis.
Genetic: Gene variants in atherosclerosis
From the blood samples of the patients, the total DNA will be extracted and the main functional variants identified in the literature will be genotyped

Other: Microbiota analysis
From the samples of blood, feces, oral cavity and blood, the DNA of the microbiota will be extracted using specific extraction kits and the microbiome will be analyzed through the study of 16S ribosomal RNA amplicons.

Other: Immunological analysis
A study of immunological cell populations and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry

Other: Clinical evaluation
Clinical evaluation including hemostasis and biochemical studies and questionaries for diet and exercice registration

ACS-Angiographic substudy

Patients included in the Acute Coronary Syndrome group with clinical indication for revascularization.

Clinical evaluation. Assessment of the atherosclerotic plaque in a moderate lession at baseline and 1-year .

Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis

Procedure: Assessment of the atherosclerotic plaque in a moderate lession.

In patients who have been successfully revascularized the artery responsible for AMI and also present an intermediate lesion (40-80%) in another coronary territory, the clinical care protocol of the Cardiology Service stipulates the need for a physiological assessment with guidance of pressure (FFR).

The thickness of the fibrous cap shall be measured using optical coherence tomography.

In addition to the FFR measurement, a complete physiological assessment with a Doppler-pressure guide. This will allow the procedure to be performed without additional risk to the patient. The physiological study will include the analysis of endothelium-dependent vascular function and endothelium-independent vascular function.

Other Name: Coronary blood collection

Genetic: Gene variants in atherosclerosis
From the blood samples of the patients, the total DNA will be extracted and the main functional variants identified in the literature will be genotyped

Other: Microbiota analysis
From the samples of blood, feces, oral cavity and blood, the DNA of the microbiota will be extracted using specific extraction kits and the microbiome will be analyzed through the study of 16S ribosomal RNA amplicons.

Other: Immunological analysis
A study of immunological cell populations and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry

Other: Clinical evaluation
Clinical evaluation including hemostasis and biochemical studies and questionaries for diet and exercice registration

Chronic coronary atherosclerosis
Patients with chronic atherosclerosis. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis.
Genetic: Gene variants in atherosclerosis
From the blood samples of the patients, the total DNA will be extracted and the main functional variants identified in the literature will be genotyped

Other: Microbiota analysis
From the samples of blood, feces, oral cavity and blood, the DNA of the microbiota will be extracted using specific extraction kits and the microbiome will be analyzed through the study of 16S ribosomal RNA amplicons.

Other: Immunological analysis
A study of immunological cell populations and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry

Other: Clinical evaluation
Clinical evaluation including hemostasis and biochemical studies and questionaries for diet and exercice registration




Primary Outcome Measures :
  1. Change from baseline in clinical evaluation at 12 months [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Cardiac events register including hemostasis and biochemical determinations

  2. Change from baseline in fibrous cap thickness at 12 months [ Time Frame: Inclusion and 12 months ]
    Angiographic substudy-Change from baseline in the thickness of the fibrous cap (μm) of an atherosclerotic plaque in the nonculprit vessel as measured using optical coherence tomography


Secondary Outcome Measures :
  1. Endothelial dysfunction [ Time Frame: Inclusion and 12 months ]
    Angiographic substudy-Micro and macrovascular endothelial function measured using a Doppler pressure guidewire

  2. Intestinal microbiota composition changes 16S [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Changes from baseline in intestinal microbiota will be analysed using the 16S rRNA target gene sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months

  3. Intestinal microbiota composition changes metagenome [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Changes from baseline in intestinal microbiota will be analysed using the metagenome sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months

  4. Blood microbiota composition changes 16S [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Changes from baseline in blood microbiota will be analysed using the 16S rRNA target gene sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months

  5. Blood microbiota composition changes metagenome [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Changes from baseline in blood microbiota will be analysed using the metagenome sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months

  6. Oral microbiota composition changes 16S [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Changes from baseline in oral microbiota will be analysed using the 16S rRNA target gene sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months

  7. Oral microbiota composition changes metagenome [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Changes from baseline in oral microbiota will be analysed using the genome sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months

  8. Adaptive immune system status changes [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Changes from baseline of adaptive immune cell lineages will be assessed dynamically using high performance cytometry at 1 week, 1 month, 3 months, 6 months and 12 months

  9. Innate immune system status changes [ Time Frame: Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months ]
    Changes from baseline of innate immune cell lineages will be assessed dynamically using high performance cytometry at 1 week, 1 month, 3 months, 6 months and 12 months


Biospecimen Retention:   Samples With DNA
Feces, blood, salive


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Acute coronary syndrome candidates for the study will be all patients with an episode of acute coronary syndrome wwho enter the Gregorio Marañón General University Hospital who meet all of the inclusion criteria and none of the exclusion criteria.

Chronic atherosclerosis candidates for the study will be all patients with chronic atherosclerosis under follow-up in the General University Hospital Gregorio Marañón that meet all the following inclusion criteria and none of the exclusion criteria.

Criteria

Inclusion Criteria Acute coronary syndrome group:

  • Diagnosis of acute coronary syndrome
  • Signature of informed consent for the study (Annex I).

Exclusion Criteria Acute coronary syndrome group:

  • Previous Ejection fraction of VI less than 30%.
  • History of heart failure
  • Systemic inflammatory diseases
  • In treatment with corticosteroids or immunomodulators
  • In treatment with antibiotics during the last month

Aditional Inclusion Criteria for angiographic substudy group:

  • Clinical indication of coronary angiography in the acute phase (in the first 72 hours after its hospital diagnosis).
  • At least one non-causal coronary lesion in a coronary segment with reference diameter> 2 mm, stenosis between 40-80%, and TIMI 3 flow in this vessel (angiographic criteria, only confirmed after performing coronary angiography)
  • Signature of informed consent for the substudy (Annex II).

Aditional Exclusion Criteria for angiographic substudy group:

  • Renal insufficiency with creatinine clearance less than 30 ml / h
  • Hepatic insufficiency: patients with cirrhosis in Child B or C stages will be excluded.

Inclusion Criteria Chronic atherosclerosis group:

  • Angiographic diagnosis, using catheterization or computed tomography of coronary atherosclerotic disease.
  • Clinical situation of stable chronic ischemic heart disease.
  • Signature of informed consent for the study (Annex III).

Exclusion Criteria Chronic atherosclerosis group:

  • Previous Ejection fraction of VI less than 30%.
  • History of heart failure
  • Systemic inflammatory diseases
  • In treatment with corticosteroids or immunomodulators
  • In treatment with antibiotics during the last month

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03434483


Contacts
Contact: Javier Bermejo, MD, PhD 34915868279 javier.bermejo@salud.madrid.org
Contact: Raquel Yotti, MD, PhD 34915868279 raquel.yotti@salud.madrid.org

Locations
Spain
Hospital General Universitario Gregorio Maranon Recruiting
Madrid, Spain, 28007
Principal Investigator: Javier Bermejo, MD, PhD         
Sub-Investigator: Raquel Yotti, MD, PhD         
Sponsors and Collaborators
Hospital General Universitario Gregorio Marañon
Fundación para la Investigación Biomédica del Hospital Gregorio Maranon
Investigators
Study Director: Francisco Fernández-Aviles, Prof, MD Hospital General Universitario Gregorio Marañón

Responsible Party: Javier Bermejo Thomas, MD PhD Cardiology Department HGUGM, Hospital General Universitario Gregorio Marañon
ClinicalTrials.gov Identifier: NCT03434483     History of Changes
Other Study ID Numbers: FIBHGM-MIGATER
PIE 16/00055 ( Other Grant/Funding Number: Instituto de Salud Carlos III )
First Posted: February 15, 2018    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Javier Bermejo Thomas, Hospital General Universitario Gregorio Marañon:
Microbiota
Immunity
Genetics
Atherosclerosis

Additional relevant MeSH terms:
Atherosclerosis
Acute Coronary Syndrome
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Myocardial Ischemia
Heart Diseases