The MISTRAL Study: Gut Microbiome Correlates of Serious AIDS and Non-AIDS Events (MISTRAL)

April 8, 2025 updated by: Jens D Lundgren, MD, Rigshospitalet, Denmark

Microbiome-based Stratification of Individuals at Risk of HIV-1 Acquisition, Chronic Clinical Complications, Antimicrobial Drug Resistance, and Unresponsiveness to Therapeutic HIV-1 Vaccination

MISTRAL (Microbiome-based stratification of individuals at risk of HIV-1 acquisition, chronic clinical complications, antimicrobial drug resistance, and unresponsiveness to therapeutic HIV-1 vaccination) is a 5-year EU Horizon 2020 project, running from 1/1/2020 - 31/12/2025.

The project is led by Fundacio Privada Institut de Recerca de la Sida-Caixa CAIXA in Barcelona and aims to explore the gut microbiota in relation to HIV-1, seeking microbiome biomarkers to support development of interventions that mitigate infection and enhance response to vaccines and therapies.

If successful, MISTRAL will benefit millions of human beings living with, or at risk of acquiring HIV-1 infection, and will produce novel concepts and technical innovations applicable to other human diseases. By doing that, MISTRAL will help to unlock the full clinical potential of the human microbiome to stratify patient outcomes and will irreversibly bring microbiome science closer to clinical practice

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Background and Rationale: The HIV/AIDS pandemic continues to be one of the major health challenges ever faced by mankind. Far from being resolved, HIV is soaring in Eastern Europe (60% increase in new infections and 27% increase in deaths since 2010) and other regions of the world despite increasing access to antiretroviral treatment . There is emerging evidence that the human microbiome impacts some of the most important clinical aspects of HIV-1 infection, including immune disorders, chronic inflammation and accelerated aging . Work in other viral diseases and cancer immunotherapy suggest a critical role of the human microbiome also in the outcome of immune therapeutic interventions in HIV-1 infection .

MISTRAL (The Microbiome-based stratification of individuals at risk of HIV-1 acquisition, chronic clinical complications, antimicrobial drug resistance, and unresponsiveness to therapeutic HIV-1 vaccination) is a European Union (EU) Horizon 2020 funded project that aims to explore the impact of the human microbiome on clinical outcomes in people living with HIV (PLWH). The MISTRAL project brings together a team of world-class HIV and microbiome researchers with ideal complementary knowledge and expertise. This team will work to discover and validate novel gut microbiome biomarkers to inform rationally designed, mechanistically-driven interventions on the gut microbiome to mitigate HIV-1 acquisition, systemic inflammation, chronic clinical complications, antimicrobial drug resistance, and boost the efficacy of HIV cure immunotherapies.

Within the MISTRAL project, the MISTRAL study will explore the impact of the microbiome on clinical outcomes in a large clinical cohort of PLWH through the collection and analysis of stool, plasma and blood samples. The MISTRAL study will utilize the long-established network, clinical sites and expertise of the EuroSIDA study, a prospective, observational cohort study of PLWH that has been collecting observational data since 1994.

The stool samples collected in the MISTRAL study will configure a microbiome repository module. The microbiome data/test results will be combined with those of other biomarkers obtainable from testing plasma and blood samples, which could result in increased efficiency and the possibility to use other biomarkers to test the relevance of specific hypothesized pathways. Ultimately, the expected outcome of the MISTRAL study is to have a better basic understanding of the pathophysiological factors of the interplay of HIV infection and the human microbiome.

Study objectives: The primary objective of the MISTRAL study is to strengthen and evaluate the understanding of the association between the gut microbiome composition and the risk of developing serious AIDS and non-AIDS events, including cardiovascular events. The second objective is to evaluate the associations between the gut microbiome composition and function and pathologic increases in inflammation and coagulation mediators in PLWH. The third objective is to develop a risk score which makes use of information in the gut microbiome as well as other risk factors separately for the different endpoints.

Study Design: As the MISTRAL study is a non-interventional observational study, data is only collected during participant visits and treatment will not be influenced by the participation. Participants will provide a stool, plasma and whole blood sample at baseline and an additional follow-up sample up to two years after baseline. Participant information about their diet, time and frequency of defecation, medication history and usage and lifestyle data will also be collected at baseline and up to two years after baseline. Clinical data including demographic, laboratory, medical treatment and clinical event history will be collected at enrolment and during annual follow-up. The biological samples will be used to conduct pre-specified analyses into microbiome and immunological related factors, as well as form the basis of an ongoing research biobank for future exploration of the impact on microbiome on clinical outcomes in PLWH. For a subset of the cohort, analyses of host-genetic material will also be performed.

Data Collection: MISTRAL study enrolment, participant information and follow-up data are captured electronically in electronic case reports forms (e-CRFs) using the free secure online browser-based Research Electronic Data Capture tool (REDCap) or RESPOND Electronic Data Submission Tool (REST). Data are collected initially into EuroSIDA servers based at CHIP. At CHIP, the clinical data will undergo quality assurance procedures before being transferred to the MISTRAL data repository for storage. The MISTRAL data repository is contained within Amazon Web Services servers located within the EU and complies with EU data protection. All data is pseudonymised. A de-coding list is held in a safe location by the individual site.

Sample Repository/Research Biobank: Stool, plasma and blood samples will initially be shipped to the coordinating centre at CHIP, Rigshospitalet, Denmark, and stored in secure holding facilities at - 80° Celsius. These samples will then be transferred to the MISTRAL biobank at IrsiCaixa, Hospital Germans Trias I Pujol, Barcelona Spain. Analyses will be performed by members of the MISTRAL Consortium. Samples will not be sent outside the European Union without data transfer agreements. A proportion of the samples collected will be stored for future, yet unspecified research. Samples will be destroyed the latest on 31 December 2045 in accordance with current legal and ethical requirements.

Safety: Participation in the MISTRAL study does not include any risk for participants. The study does not test or investigate any treatments and participation in this study does not interfere with the treatment/care participants may receive at the clinic. There are no direct benefits to the participants. However, the benefit of conducting observational research that includes analysis of biological samples will advance scientific understanding of HIV infection and other co-infections and co-morbidities as well as their complications. This knowledge guides international and European treatment recommendations for the benefit of PLWH and national health systems.

Economy: Sites participating in the MISTRAL study will be reimbursed for enrolment and follow up data collection for each participant, event forms and sending samples.

The MISTRAL study has received funding from the European Commission Directorate-General for Research and Innovation Horizon 2020 Grant Agreement number 847943 (9,994,383.75€).

Participants in the study receive no financial compensation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
991

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Belgium
      • Brussels, Belgium, 1000
        • CHU Saint-Pierre Hospital
  • Croatia
      • Zagreb, Croatia
        • University Hospital of Infectious Diseases
  • Czechia
      • Prague, Czechia
        • Faculty Hospital Bulovka
  • Denmark
      • Aarhus, Denmark, 8200
        • Aarhus University Hospital
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
      • Hvidovre, Denmark
        • Hvidovre Universitets Hospital
      • Odense, Denmark, 5000
        • Odense Universitetshospital
  • Germany
      • Bonn, Germany
        • University Hospital Bonn, Klinisches StudieZentrum Immun.
      • Cologne, Germany
        • University Hospital Cologne
      • Eppendorf, Germany
        • University Clinic Hamburg Eppendorf
      • Frankfurt am Main, Germany
        • J.W.Goethe University Hospital
      • Hamburg, Germany
        • ICH Study Center, Innere Medizin
  • Israel
      • Jerusalem, Israel
        • Hadassah Hospital
  • Italy
      • Milano, Italy
        • Ospedale San Paulo
  • Luxembourg
      • Luxembourg, Luxembourg
        • Centre Hospitalier de Luxembourg
  • Poland
      • Lodz, Poland
        • Wojewodzki Szpital Specjalistyczny im. WI. Bieganskiego
  • Spain
      • Badalona, Spain
        • Hosp. Universitari Germans Trias i Pujol, Hospital de dia VIH
      • Barcelona, Spain
        • Hospital de La Santa Creu i Sant Pau
  • United Kingdom
      • Brighton, United Kingdom
        • Royal Sussex County Hospital, HIV/GUM Research
      • Edinburgh, United Kingdom
        • Western General Hospital
      • London, United Kingdom
        • Imperial College
      • London, United Kingdom
        • University College London, Mortimer Market Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Participating sites will recruit HIV-1 positive persons age 50 years or older with no prior events who are prospectively followed in a EuroSIDA site

Description

Inclusion Criteria:

  • HIV-1 positive persons
  • Age ≥50 years old
  • Prospectively followed in a EuroSIDA site

Exclusion Criteria:

  • Creatine Clearance <50
  • Child-Pugh C end-stage liver disease
  • Any ongoing severe life-threatening disease
  • Experiencing any of the following events prior to inclusion: myocardial infarction, stroke, an invasive cardiovascular procedure, AIDS-defining infections (diagnosed with 5 years of MISTRAL enrolment), and prior AIDS cancer on non-AIDS cancers (excluding non-melanoma skin cancers)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
PLWH ≥50 years old

HIV-1 positive persons, Age ≥50 years old, prospectively followed in a EuroSIDA site

Exclusion Criteria: Creatine Clearance <50, Child-Pugh C end-stage liver disease, Any ongoing severe life-threatening disease, Experiencing any of the following events prior to inclusion: myocardial infarction, stroke, an invasive cardiovascular procedure, AIDS-defining infections (diagnosed with 5 years of MISTRAL enrolment), and prior AIDS cancer on non-AIDS cancers (excluding non-melanoma skin cancers)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of serious AIDS and non-AIDS events
Time Frame: From date of enrolment until lost to follow-up or death, whichever came first, assessed up to 5 years
In particular cardiovascular events, across Europe; and multi-omics (in particular gut microbiome), demographic, dietary, clinical, therapeutic, immunological and viral factors associated with these outcomes
From date of enrolment until lost to follow-up or death, whichever came first, assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Rigshospitalet, Denmark

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Horizon 2020 - European Commission
IrsiCaixa

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jens Lundgren, Professor, CHIP, Rigshospitalet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 28, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 16, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 11, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • The MISTRAL Study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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