Host-Pathogen InteractionsPATHO-NATNCT05981378
Genomic Approaches to Dissect Human Host-pathogen Interactions in the Amazonian Rainforest
An observational study of Host-Pathogen Interactions, run by Universidad Peruana Cayetano Heredia.
Trial summary
This observational study, aims to characterize with a multi-omic approach, the impact of host genetics and the pathogenic environment on immune response variation in Native Amazonians in comparison with Mestizo Amazonian, a severely underrepresented population in genomic studies. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Host-Pathogen Interactions
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- 2 Aug 2024to 30 Jan 2025
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Amazonian Peruvian Native American and Amazonian mestizo population between 2023-2024
Who may be able to join
- People over 18 years of age who agree to participate in the study and sign the informed consent
- People whose parents and grandparents were born in the Peruvian Amazon.
- For volunteers from native communities, whose parents and grandparents belong to the same native community.
Who cannot join
- People who do not wish to have 40 mL of blood taken
- People who are passing through a febrile illness (fever during the last 5 days to the date of enrollment).
- Pregnant women
- People over 65 years old
- Breastfeeding women.
Trial locations and contacts
No sites are listed yet.
About this study
This observational study, aims to characterize with a multi-omic approach, the impact of host genetics and the pathogenic environment on immune response variation in Native Amazonians in comparison with Mestizo Amazonian, a severely underrepresented population in genomic studies.
Various samples will be taken from the participants, including blood, urine, saliva, etc. From the blood sample, peripheral blood mononuclear cells will be obtained and will give us information about the differences between immune response variation of Amazonian population. From the other samples we will be able to obtain additional information on the risk factors related to the difference in the immune response of the participants.
Read the detailed description
The Amazon rainforest is characterized by adverse climatic conditions and a great diversity of pathogenic microorganisms that, consequently, would generate a selective pressure on the human immune response with a high impact on mortality. Some of the best characterized examples of human genetic adaptation have been related to infections; for example, the alleles causing sickle cell anemia, thalassemia and malaria. In addition, the introduction of infectious diseases from the "old world" during Spanish colonization in the 15th century and the urbanization of the last few centuries in the Amazon has also generated rapid adaptation that could drive variation in immune response. However, the evolutionary mechanisms that contributed to the adaptation of human defense against the aforementioned phenomena and events in this region are poorly understood. For this reason, studying these human genetic mechanisms in native populations would allow us to identify new genes that would be associated with resistance to infections, and also to explore the signs of rapid adaptation to the environment to which Amazonian populations have been exposed throughout their history.
We propose to study the variation of the immune system in Amazonian populations, studying together the degree of diversity with different approaches: genomic, epi-genomic and transcriptomic of the host and viral exposome, taking into consideration sociodemographic characteristics and comorbidities, which may shape the immune response. This study will provide new insights into variants in the human genome that affect the immune response, thereby increasing our understanding of the etiology and susceptibility to immune-related diseases, mainly tropical infectious diseases. Because human genetic studies are underrepresented in Native American populations, the knowledge gained would reduce the existing inequality in health knowledge between Native and non-Native populations.
- Conditions
- Host-Pathogen Interactions
- Keywords
- Tropical Rainforest, Genomics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Native Amazonian group | Amazonian people that belongs to a indigenous community located in the Peruvian Amazon | |
| Urban Amazonian mestizos group | Amazonian mestizo people that lives on a urban district in the Peruvian Amazon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genes showing different transcriptional profiles and methylation pattern according environment, genetic ancestry and past viral exposure
We will measure genome-wide expression profiles in peripheral blood mononuclear cells after stimulation for 6 hours with: (i) dengue virus, a major public health burden in the region, (ii) gardiquimod, an imidazoquinoxaline compound that activates toll like receptor 7/toll like receptor 8, able to sense viruses and intracellular pathogens; and (iii) lipopolysaccharide, a toll like receptor 4 agonist, to obtain a general view of responses to viruses and bacteria.
Gene expression profiles will be measured using RNA-seq.
Measured: Baseline
Genetic and epigenetic diversity of amazonian population
Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.
Measured: Baseline
Impact of microbial exposures on immune response
The viral exposome will be characterized in the 300 donors using a new tool call "VirScan", which identifies antibodies against >600 pathogens and allergens, including viruses (>1,200 viral strains) that are highly prevalent in the Amazonian, such as dengue, hepatitis B/C/D, or Mayaro virus.
Measured: Baseline
Genetic variants associated wit transcriptional response to immune activation and DNA methylation variation
We will assess the host genetic factors controlling transcriptional responses and methylated DNA levels by mapping expression and methylation quantitative trait loci (eQTL and methylated eQTLs, respectively).
Measured: Baseline
Secondary outcomes (2)
Demographic and admixture history of amazonian population
Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.
Measured: Baseline
Natural selection role in shaping immune response variation in Amazonians
We will employ an enrichment approach to test whether eQTLs, associated to specific cell-types or conditions, have been preferentially targeted by selection.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2023
- Study start2 Aug 2024 (estimated)
- Primary completion20 Nov 2024 (estimated)
- Study completion30 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Host-Pathogen InteractionsStudies 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
- Other
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidad Peruana Cayetano Heredia
- Sponsor type
- University, hospital or other
- Collaborators
- Institut Pasteur
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05981378
- Sponsor's protocol ID
- 210828
- Acronym
- PATHO-NAT
- Status last verified
- Apr 2024
- First submitted
- 31 Jul 2023
- Last updated
- 24 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genomic Approaches to Dissect Human Host-pathogen Interactions in the Amazonian Rainforest
- ClinicalTrials.gov ID
- NCT05981378
- Acronym / sponsor ID
- PATHO-NAT / 210828
- Conditions
- Host-Pathogen Interactions
- Keywords
- Tropical Rainforest, Genomics
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Universidad Peruana Cayetano HerediaUniversity, hospital or other
- Collaborators
- Institut Pasteur
- Study start
- 2 Aug 2024 (estimated)
- Primary completion
- 20 Nov 2024 (estimated)
- Study completion
- 30 Jan 2025 (estimated)
- First posted
- 8 Aug 2023 (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 observational study, aims to characterize with a multi-omic approach, the impact of host genetics and the pathogenic environment on immune response variation in Native Amazonians in comparison with Mestizo Amazonian, a severely underrepresented population in genomic studies.
Various samples will be taken from the participants, including blood, urine, saliva, etc. From the blood sample, peripheral blood mononuclear cells will be obtained and will give us information about the differences between immune response variation of Amazonian population. From the other samples we will be able to obtain additional information on the risk factors related to the difference in the immune response of the participants.
Detailed description
The Amazon rainforest is characterized by adverse climatic conditions and a great diversity of pathogenic microorganisms that, consequently, would generate a selective pressure on the human immune response with a high impact on mortality. Some of the best characterized examples of human genetic adaptation have been related to infections; for example, the alleles causing sickle cell anemia, thalassemia and malaria. In addition, the introduction of infectious diseases from the "old world" during Spanish colonization in the 15th century and the urbanization of the last few centuries in the Amazon has also generated rapid adaptation that could drive variation in immune response. However, the evolutionary mechanisms that contributed to the adaptation of human defense against the aforementioned phenomena and events in this region are poorly understood. For this reason, studying these human genetic mechanisms in native populations would allow us to identify new genes that would be associated with resistance to infections, and also to explore the signs of rapid adaptation to the environment to which Amazonian populations have been exposed throughout their history.
We propose to study the variation of the immune system in Amazonian populations, studying together the degree of diversity with different approaches: genomic, epi-genomic and transcriptomic of the host and viral exposome, taking into consideration sociodemographic characteristics and comorbidities, which may shape the immune response. This study will provide new insights into variants in the human genome that affect the immune response, thereby increasing our understanding of the etiology and susceptibility to immune-related diseases, mainly tropical infectious diseases. Because human genetic studies are underrepresented in Native American populations, the knowledge gained would reduce the existing inequality in health knowledge between Native and non-Native populations.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Native Amazonian group | – | –Amazonian people that belongs to a indigenous community located in the Peruvian Amazon |
| Urban Amazonian mestizos group | – | –Amazonian mestizo people that lives on a urban district in the Peruvian Amazon |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Amazonian Peruvian Native American and Amazonian mestizo population between 2023-2024
Key inclusion criteria (3 listed)
- People over 18 years of age who agree to participate in the study and sign the informed consent
- People whose parents and grandparents were born in the Peruvian Amazon.
- For volunteers from native communities, whose parents and grandparents belong to the same native community.
Key exclusion criteria (5 listed)
- People who do not wish to have 40 mL of blood taken
- People who are passing through a febrile illness (fever during the last 5 days to the date of enrollment).
- Pregnant women
- People over 65 years old
- 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
Genes showing different transcriptional profiles and methylation pattern according environment, genetic ancestry and past viral exposure
Time frame: Baseline
We will measure genome-wide expression profiles in peripheral blood mononuclear cells after stimulation for 6 hours with: (i) dengue virus, a major public health burden in the region, (ii) gardiquimod, an imidazoquinoxaline compound that activates toll like receptor 7/toll like receptor 8, able to sense viruses and intracellular pathogens; and (iii) lipopolysaccharide, a toll like receptor 4 agonist, to obtain a general view of responses to viruses and bacteria. Gene expression profiles will be measured using RNA-seq.
Genetic and epigenetic diversity of amazonian population
Time frame: Baseline
Using saliva from participants as source of DNA, we will perform whole-genome sequencing (WGS) at 8-10xcoverage.
Impact of microbial exposures on immune response
Time frame: Baseline
The viral exposome will be characterized in the 300 donors using a new tool call "VirScan", which identifies antibodies against >600 pathogens and allergens, including viruses (>1,200 viral strains) that are highly prevalent in the Amazonian, such as dengue, hepatitis B/C/D, or Mayaro virus.
Genetic variants associated wit transcriptional response to immune activation and DNA methylation variation
Time frame: Baseline
We will assess the host genetic factors controlling transcriptional responses and methylated DNA levels by mapping expression and methylation quantitative trait loci (eQTL and methylated eQTLs, respectively).
2 secondary outcomes
Demographic and admixture history of amazonian population
Time frame: Baseline
Natural selection role in shaping immune response variation in Amazonians
Time frame: Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2024.
- Web page of the ethical review board of Universidad Peruana Cayetano HerediaLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Host-Pathogen Interactions, run by Universidad Peruana Cayetano Heredia.
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 5 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: status not confirmed, as of the sponsor's last update on 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Meddly Santoalla, PhD (+51 914068043, meddly.santolalla.r@upch.pe), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genes showing different transcriptional profiles and methylation pattern according environment, genetic ancestry and past viral exposure (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Apr 2024.