Vaccine ReactionPhase 4NCT06266754
The Non-Specific Immunological Effects of Providing Oral Polio Vaccine to Seniors in Guinea-Bissau
A Phase 4 study testing Oral polio vaccine in people with Vaccine Reaction, run by Bandim Health Project at 1 site in Guinea-Bissau.
Trial summary
OPV is the live attenuated vaccine against polio virus. OPV has been key in almost eradicating polio infection. Intriguingly, OPV has been associated with lower all-cause mortality and morbidity. Read more about this study
- Who is it for?
- Ages 50 to 120 years, men only
- Conditions the study is for
- Vaccine Reaction
- What is being tested?
- Oral polio vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteGuinea-Bissau
- Study dates
- 29 Jan 2024to 31 Dec 2024
- Phase
- Phase 4
- 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 50 to 120 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male.
- Living in a household which had a Bandim Health Project census visit conducted after 1 January 2017.
- Age above 50.
- Has a visible BCG scar.
Who cannot join
- Previous adverse events to OPV
- Suspicion of active viral/bacterial/HIV infection.
Trial locations and contacts
1 site in 1 country.
About this study
OPV is the live attenuated vaccine against polio virus. OPV has been key in almost eradicating polio infection. Intriguingly, OPV has been associated with lower all-cause mortality and morbidity. These beneficial OPV effects were seen in contexts with no circulating polio virus and thus have nothing to do with the specific effects of OPV against polio infection. They have been coined "non-specific effects" (NSEs). Such NSEs have also been observed for other live attenuated vaccines such as BCG vaccine and measles vaccine. The underlying immunological mechanisms are unknown. Other live vaccines with beneficial NSEs have been shown to induce epigenetic changes leading to "trained immunity". They have also been associated with decreased inflammation. In the present study it will be investigates whether OPV can induce trained immunity, reduce inflammation, and induce epigenetic modifications of the innate immune cells in senior citizens in Guinea-Bissau.
Read the detailed description
The aim is to study the non-specific immunological effects of providing a single dose of OPV to seniors aged 50 and above in Guinea-Bissau:
Hypotheses
- OPV induces innate immune training (substudy A)
- OPV is associated with reduced systemic inflammation (substudy A)
- OPV induces epigenetic modifications of the innate immune cells (substudy B)
Setting: Bandim Health Project (BHP)'s Health and Demographic Surveillance System (HDSS) in Bissau.
Design: Individually randomized trial in BHP's study area. Participants will be randomized 1:1 to OPV or placebo. To limit the amount of blood drawn from one single participant, two substudies with similar design will be conducted, with two different outcomes.
The outcomes of the two substudies will be as follows:
Substudy A: Immunological impact of OPV. Study the stimulation of cytokine production by heterologous stimuli as a biomarker of trained immunity induction and circulating biomarkers as a mirror of systemic inflammation induced by OPV.
Substudy B: Transcriptional and epigenetic reprogramming of immune cells by OPV. Study the transcriptional and epigenetic rewiring of immune cells induced by OPV by single-cell ATAC-Sequencing and RNA-Sequencing.
- Conditions
- Vaccine Reaction
- Being tested
- Oral polio vaccine, Placebo
- Keywords
- Oral polio vaccine, Trained immunity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral polio vaccineBiological
Standard oral polio vaccine
PlaceboOther
Saline 0.9%
| Study group | Role | What they receive |
|---|---|---|
| Oral polio vaccine | Experimental | Oral polio vaccine, 2 drops on a sugar lump Receives: Biological: Oral polio vaccine |
| Placebo | Placebo comparator | Saline, 2 drops on a sugar lump Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of in vitro proinflammatory cytokines such as IL1-beta, TNF-alfa and IFN-gamma after stimulation of peripheral blood mononuclear cells with non-OPV antigens and mitogens
Study the ability of cells of producing cytokines in vitro after heterologous stimuli. This is a well-established biomarker of trained immunity (ref: https://pubmed.ncbi.nlm.nih.gov/38198850/).
Measured: 1 month after the intervention
Levels of plasma markers of systemic inflammation such as TNF ligand superfamily member 12 (TWEAK) and sirtuin 2 (SIRT2)
Study the effect on systemic inflammation induced by OPV. Previous studies have shown that BCG reduce up to a third of proinflammatory proteins as a marker of non-specific effects of that vaccine, we will study if this is the case also for OPV (ref:https://pubmed.ncbi.nlm.nih.gov/32692728/).
Measured: 1 month after the intervention
Amount of pseudo-bulk ATACseq and RNAseq - indicating chromatin accessibility of interferon-stimulated genes associated with the interferon response pathway in PBMCs.
Study the epigenetic rewiring of immune cells induced by OPV by single-cell ATAC-Sequencing and whole-genome methylation assays. This is a new method to assess if there has been changes to the accessibility of the genes (ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022455/).
Measured: 1 month after the intervention
Proportions of immune cell subsets
Study the transcriptional effects of OPV on immune cell by studying the transcriptional rewiring of immune cells induced by OPV by single-cell RNA-Sequencing (ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022455/).
Measured: 1 month after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start29 Jan 2024
- Primary completion31 Jul 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vaccine ReactionStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bandim Health Project
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center
- Responsible party
- Sponsor
- Investigators
- Anne Marie R Madsen, MD, PhD, Principal investigator, Bandim Health Project
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06266754
- Sponsor's protocol ID
- OPV-IMMUNO-ADULT
- Status last verified
- Feb 2024
- First submitted
- 18 Jan 2024
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We collect sensitive data that cannot immediately be shared.
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Non-Specific Immunological Effects of Providing Oral Polio Vaccine to Seniors in Guinea-Bissau
- ClinicalTrials.gov ID
- NCT06266754
- Acronym / sponsor ID
- OPV-IMMUNO-ADULT
- Conditions
- Vaccine Reaction
- Keywords
- Oral polio vaccine, Trained immunity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Bandim Health ProjectUniversity, hospital or other
- Collaborators
- Radboud University Medical Center
- Study start
- 29 Jan 2024 (actual)
- Primary completion
- 31 Jul 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 20 Feb 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.
OPV is the live attenuated vaccine against polio virus. OPV has been key in almost eradicating polio infection. Intriguingly, OPV has been associated with lower all-cause mortality and morbidity. These beneficial OPV effects were seen in contexts with no circulating polio virus and thus have nothing to do with the specific effects of OPV against polio infection. They have been coined "non-specific effects" (NSEs). Such NSEs have also been observed for other live attenuated vaccines such as BCG vaccine and measles vaccine. The underlying immunological mechanisms are unknown. Other live vaccines with beneficial NSEs have been shown to induce epigenetic changes leading to "trained immunity". They have also been associated with decreased inflammation. In the present study it will be investigates whether OPV can induce trained immunity, reduce inflammation, and induce epigenetic modifications of the innate immune cells in senior citizens in Guinea-Bissau.
Detailed description
The aim is to study the non-specific immunological effects of providing a single dose of OPV to seniors aged 50 and above in Guinea-Bissau:
Hypotheses
- OPV induces innate immune training (substudy A)
- OPV is associated with reduced systemic inflammation (substudy A)
- OPV induces epigenetic modifications of the innate immune cells (substudy B)
Setting: Bandim Health Project (BHP)'s Health and Demographic Surveillance System (HDSS) in Bissau.
Design: Individually randomized trial in BHP's study area. Participants will be randomized 1:1 to OPV or placebo. To limit the amount of blood drawn from one single participant, two substudies with similar design will be conducted, with two different outcomes.
The outcomes of the two substudies will be as follows:
Substudy A: Immunological impact of OPV. Study the stimulation of cytokine production by heterologous stimuli as a biomarker of trained immunity induction and circulating biomarkers as a mirror of systemic inflammation induced by OPV.
Substudy B: Transcriptional and epigenetic reprogramming of immune cells by OPV. Study the transcriptional and epigenetic rewiring of immune cells induced by OPV by single-cell ATAC-Sequencing and RNA-Sequencing.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised trial
| Arm | Type | Receives |
|---|---|---|
| Oral polio vaccine | Experimental | Biological: Oral polio vaccineOral polio vaccine, 2 drops on a sugar lump |
| Placebo | Placebo comparator | Other: PlaceboSaline, 2 drops on a sugar lump |
Who may qualify
- Ages
- 50 to 120 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male.
- Living in a household which had a Bandim Health Project census visit conducted after 1 January 2017.
- Age above 50.
- Has a visible BCG scar.
Key exclusion criteria (2 listed)
- Previous adverse events to OPV
- Suspicion of active viral/bacterial/HIV infection.
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 |
|---|---|---|
| Oral polio vaccineStandard oral polio vaccine | Biological | Oral polio vaccine |
| PlaceboSaline 0.9% | Other | Placebo |
Primary outcome
Levels of in vitro proinflammatory cytokines such as IL1-beta, TNF-alfa and IFN-gamma after stimulation of peripheral blood mononuclear cells with non-OPV antigens and mitogens
Time frame: 1 month after the intervention
Study the ability of cells of producing cytokines in vitro after heterologous stimuli. This is a well-established biomarker of trained immunity (ref: https://pubmed.ncbi.nlm.nih.gov/38198850/).
Levels of plasma markers of systemic inflammation such as TNF ligand superfamily member 12 (TWEAK) and sirtuin 2 (SIRT2)
Time frame: 1 month after the intervention
Study the effect on systemic inflammation induced by OPV. Previous studies have shown that BCG reduce up to a third of proinflammatory proteins as a marker of non-specific effects of that vaccine, we will study if this is the case also for OPV (ref:https://pubmed.ncbi.nlm.nih.gov/32692728/).
Amount of pseudo-bulk ATACseq and RNAseq - indicating chromatin accessibility of interferon-stimulated genes associated with the interferon response pathway in PBMCs.
Time frame: 1 month after the intervention
Study the epigenetic rewiring of immune cells induced by OPV by single-cell ATAC-Sequencing and whole-genome methylation assays. This is a new method to assess if there has been changes to the accessibility of the genes (ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022455/).
Proportions of immune cell subsets
Time frame: 1 month after the intervention
Study the transcriptional effects of OPV on immune cell by studying the transcriptional rewiring of immune cells induced by OPV by single-cell RNA-Sequencing (ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022455/).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Individual participant dataSharing planned: No. We collect sensitive data that cannot immediately be shared.
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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.
Anne Marie R Madsen, MD, PhD principal investigator
Bandim Health Project
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oral polio vaccine in people with Vaccine Reaction, run by Bandim Health Project at 1 site in Guinea-Bissau.
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 2 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 20 Feb 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 Guinea-Bissau. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
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?
Levels of in vitro proinflammatory cytokines such as IL1-beta, TNF-alfa and IFN-gamma after stimulation of peripheral blood mononuclear cells with non-OPV antigens and mitogens (time frame: 1 month after the intervention). 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 20 Feb 2024.