Immune ModulationNCT03084614
CD8 Reactivity to Microorganisms in Blood and Breast Milk
An observational study of Immune Modulation and Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: When a person is exposed to something that causes an infection, the body sends a type of cell called CD8 T cells to attack it. Those cells are also found in breast milk. Nursing mothers pass these cells to their child, which helps the child fight infections, too. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Immune Modulation, Tuberculosis, Leprosy
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2017to 8 Nov 2019
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: clinical center patients, family members, healthy controls
Who may be able to join
None listed.
Who cannot join
- Active use of immunosuppressive medications.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
When a person is exposed to something that causes an infection, the body sends a type of cell called CD8 T cells to attack it. Those cells are also found in breast milk. Nursing mothers pass these cells to their child, which helps the child fight infections, too. Researchers want to learn more about how CD8 cells work to keep people healthy.
Read more
Objective:
To learn more about how the human body fights off infections.
Eligibility:
People age 18 years and older who either have an infection, are suspected to have an infection, or recently got a vaccine.
The household contacts of these people and people who have not been recently exposed to any infection are also needed.
Design:
Participants will be screened with a medical and health history and physical exam. They may have blood tests.
The first study visit can be the same day as screening. It can be up to 3 months later. For those visits, screening tests will be repeated.
At the first visit, participants will have blood collected from an arm vein.
Participants who are breastfeeding may provide a small sample of breast milk. They may collect it at home or bring a pumping device to NIH to collect it. NIH can also provide a breast pump.
Participants may be contacted for up to 1 year after the first visit to give samples of blood and/or breast milk.
Up to 4 additional visits, which will each take about 1 hour, may be scheduled.
A personal physician or local lab can collect blood from participants and ship it to NIH. Breast milk cannot be shipped.
Read the detailed description
Cellular lysates from purified protein derivative-positive donors have been reported to transfer tuberculin reactivity to na(SqrRoot) ve recipients, but not diphtheria reactivity; similarly, cell lysates from diphtheria-reactive donors appear to transfer diphtheria reactivity without impacting responses to tuberculin. A historically controversial topic, the terms transfer factor and dialyzed leukocyte extract were used to characterize the reactivity-transferring properties of lysates. We found that the cellular extract derived from antigen-specific memory CD8+ T cells induces interleukin (IL)-6 from antigen-matched antigen-presenting cells. This ultimately elicits IL-17 from bystander memory CD8+ T cells. We identified that dialyzable peptide sequences, S100a9, and the TCR <= chain from CD8+ T cells contribute to the molecular nature of this activity. We further showed that extracts from antigen-targeted T cells enhance immunity to Staphylococcus aureus and Candida albicans. The observed anti-Candida activity of lysates was enhanced when the cells were taken from individuals with higher-than-average exposure to Candida and correlated with increased numbers of Candida-reactive T-cells. These effects are sensitive to immunization protocols and extraction methodology in ways that may explain past discrepancies in the reproducibility of passive cellular immunity. Work by other groups has revealed that memory CD8+ T cells are also the only cell population enriched in breast milk as compared to an equal volume of peripheral blood. Taken together, it may be that the CD8+ memory T cells in breast milk serve as a mechanism of passive cellular immunity transference from mother to offspring. We thus aim to expand our analysis into the potential that lysates taken from sources with enriched immunity against a given microorganism will induce greater in vivo and mouse model activity compared to lysates from non-immune sources, and that this difference in lysate activity will be directly related to the CD8+ T cell enrichment.
In this study, we will collect blood and/or breast milk samples from donors with known or suspected exposure to pathogens, and also from healthy non-exposed volunteers. Research evaluations of samples will be done for the relevant microbe(s) of interest. The volume of blood taken from lacting mothers will be limited to 20mL or less per visit. Cells may be proliferated, immortalized, lysed and dialyzed, and/or stored. Cellular lysates will subsequently be used in both in vitro and pre-clinical animal models to assess for therapeutic potential.
- Conditions
- Immune Modulation, Tuberculosis, Leprosy, Pertussis, Lyme Disease
- Keywords
- Infectious Diseases, Dendritic Cells, Pathogens, Passive Cellular Immunity
- Medical subject headings
- Tuberculosis, Leprosy, Whooping Cough, Lyme Disease, Communicable Diseases
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 |
|---|---|---|
| Controls | non exposed controls | |
| donors with naturally enriched antimicrobial blood samples and | Donors with naturally enriched antimicrobial blood samples an breast milk, Comparisons will be made with non exposed controls. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the in vitro and mouse model immune stimulatoryproperties of lysates derived from microbe-specific CDB+ T cellenriched sources.
Measured: There are no definitive time points in this sample collection study
Secondary outcomes (1)
To compare how the in vitro and mouse model immune stimulatoryproperties of breast milk vary with the microbe specific CDB+ T cellconcentration.
Measured: There are no definitive time points in this sample collection study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2017
- Study start28 Mar 2017
- Primary completion16 Feb 2018
- Study completion8 Nov 2019
Why it stopped: Slow/insufficient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Immune ModulationStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ian A Myles, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03084614
- Sponsor's protocol ID
- 170068
- Other IDs
- 17-I-0068
- Status last verified
- Nov 2019
- First submitted
- 15 Mar 2017
- Last updated
- 14 Nov 2019
- Results posted
- No
Publications
Myles IA, Zhao M, Nardone G, Olano LR, Reckhow JD, Saleem D, Break TJ, Lionakis MS, Myers TG, Gardina PJ, Kirkpatrick CH, Holland SM, Datta SK. CD8+ T cells produce a dialyzable antigen-specific activator of dendritic cells. J Leukoc Biol. 2017 Jan;101(1):307-320. doi: 10.1189/jlb.3A0216-082R. Epub 2016 Aug 11.
PubMed 27515950Viza D, Fudenberg HH, Palareti A, Ablashi D, De Vinci C, Pizza G. Transfer factor: an overlooked potential for the prevention and treatment of infectious diseases. Folia Biol (Praha). 2013;59(2):53-67. doi: 10.14712/fb2013059020053.
PubMed 23746171Chahroudi A, Cartwright E, Lee ST, Mavigner M, Carnathan DG, Lawson B, Carnathan PM, Hashempoor T, Murphy MK, Meeker T, Ehnert S, Souder C, Else JG, Cohen J, Collman RG, Vanderford TH, Permar SR, Derdeyn CA, Villinger F, Silvestri G. Target cell availability, rather than breast milk factors, dictates mother-to-infant transmission of SIV in sooty mangabeys and rhesus macaques. PLoS Pathog. 2014 Mar 6;10(3):e1003958. doi: 10.1371/journal.ppat.1003958. eCollection 2014 Mar.
PubMed 24604066
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD8 Reactivity to Microorganisms in Blood and Breast Milk
- ClinicalTrials.gov ID
- NCT03084614
- Acronym / sponsor ID
- 170068
- Conditions
- Immune Modulation, Tuberculosis, Leprosy, Pertussis, Lyme Disease
- Keywords
- Infectious Diseases, Dendritic Cells, Pathogens, Passive Cellular Immunity
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Slow/insufficient accrual
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 28 Mar 2017 (actual)
- Primary completion
- 16 Feb 2018 (actual)
- Study completion
- 8 Nov 2019 (actual)
- First posted
- 21 Mar 2017 (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.
Background:
When a person is exposed to something that causes an infection, the body sends a type of cell called CD8 T cells to attack it. Those cells are also found in breast milk. Nursing mothers pass these cells to their child, which helps the child fight infections, too. Researchers want to learn more about how CD8 cells work to keep people healthy.
Objective:
To learn more about how the human body fights off infections.
Eligibility:
People age 18 years and older who either have an infection, are suspected to have an infection, or recently got a vaccine.
The household contacts of these people and people who have not been recently exposed to any infection are also needed.
Design:
Participants will be screened with a medical and health history and physical exam. They may have blood tests.
The first study visit can be the same day as screening. It can be up to 3 months later. For those visits, screening tests will be repeated.
At the first visit, participants will have blood collected from an arm vein.
Participants who are breastfeeding may provide a small sample of breast milk. They may collect it at home or bring a pumping device to NIH to collect it. NIH can also provide a breast pump.
Participants may be contacted for up to 1 year after the first visit to give samples of blood and/or breast milk.
Up to 4 additional visits, which will each take about 1 hour, may be scheduled.
A personal physician or local lab can collect blood from participants and ship it to NIH. Breast milk cannot be shipped.
Detailed description
Cellular lysates from purified protein derivative-positive donors have been reported to transfer tuberculin reactivity to na(SqrRoot) ve recipients, but not diphtheria reactivity; similarly, cell lysates from diphtheria-reactive donors appear to transfer diphtheria reactivity without impacting responses to tuberculin. A historically controversial topic, the terms transfer factor and dialyzed leukocyte extract were used to characterize the reactivity-transferring properties of lysates. We found that the cellular extract derived from antigen-specific memory CD8+ T cells induces interleukin (IL)-6 from antigen-matched antigen-presenting cells. This ultimately elicits IL-17 from bystander memory CD8+ T cells. We identified that dialyzable peptide sequences, S100a9, and the TCR <= chain from CD8+ T cells contribute to the molecular nature of this activity. We further showed that extracts from antigen-targeted T cells enhance immunity to Staphylococcus aureus and Candida albicans. The observed anti-Candida activity of lysates was enhanced when the cells were taken from individuals with higher-than-average exposure to Candida and correlated with increased numbers of Candida-reactive T-cells. These effects are sensitive to immunization protocols and extraction methodology in ways that may explain past discrepancies in the reproducibility of passive cellular immunity. Work by other groups has revealed that memory CD8+ T cells are also the only cell population enriched in breast milk as compared to an equal volume of peripheral blood. Taken together, it may be that the CD8+ memory T cells in breast milk serve as a mechanism of passive cellular immunity transference from mother to offspring. We thus aim to expand our analysis into the potential that lysates taken from sources with enriched immunity against a given microorganism will induce greater in vivo and mouse model activity compared to lysates from non-immune sources, and that this difference in lysate activity will be directly related to the CD8+ T cell enrichment.
In this study, we will collect blood and/or breast milk samples from donors with known or suspected exposure to pathogens, and also from healthy non-exposed volunteers. Research evaluations of samples will be done for the relevant microbe(s) of interest. The volume of blood taken from lacting mothers will be limited to 20mL or less per visit. Cells may be proliferated, immortalized, lysed and dialyzed, and/or stored. Cellular lysates will subsequently be used in both in vitro and pre-clinical animal models to assess for therapeutic potential.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Controls | – | –non exposed controls |
| donors with naturally enriched antimicrobial blood samples and | – | –Donors with naturally enriched antimicrobial blood samples an breast milk, Comparisons will be made with non exposed controls. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- clinical center patients, family members, healthy controls
Key inclusion criteria (0 listed)
Key exclusion criteria (2 listed)
- Active use of immunosuppressive medications.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
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
To compare the in vitro and mouse model immune stimulatoryproperties of lysates derived from microbe-specific CDB+ T cellenriched sources.
Time frame: There are no definitive time points in this sample collection study
1 secondary outcome
To compare how the in vitro and mouse model immune stimulatoryproperties of breast milk vary with the microbe specific CDB+ T cellconcentration.
Time frame: There are no definitive time points in this sample collection study
Results and safety
The study was stopped early (reason given: Slow/insufficient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
- Background: PubMed 27515950Myles IA, Zhao M, Nardone G, Olano LR, Reckhow JD, Saleem D, Break TJ, Lionakis MS, Myers TG, Gardina PJ, Kirkpatrick CH, Holland SM, Datta SK. CD8+ T cells produce a dialyzable antigen-specific activator of dendritic cells. J Leukoc Biol. 2017 Jan;101(1):307-320. doi: 10.1189/jlb.3A0216-082R. Epub 2016 Aug 11.
- Background: PubMed 23746171Viza D, Fudenberg HH, Palareti A, Ablashi D, De Vinci C, Pizza G. Transfer factor: an overlooked potential for the prevention and treatment of infectious diseases. Folia Biol (Praha). 2013;59(2):53-67. doi: 10.14712/fb2013059020053.
- Background: PubMed 24604066Chahroudi A, Cartwright E, Lee ST, Mavigner M, Carnathan DG, Lawson B, Carnathan PM, Hashempoor T, Murphy MK, Meeker T, Ehnert S, Souder C, Else JG, Cohen J, Collman RG, Vanderford TH, Permar SR, Derdeyn CA, Villinger F, Silvestri G. Target cell availability, rather than breast milk factors, dictates mother-to-infant transmission of SIV in sooty mangabeys and rhesus macaques. PLoS Pathog. 2014 Mar 6;10(3):e1003958. doi: 10.1371/journal.ppat.1003958. eCollection 2014 Mar.
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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.
Ian A Myles, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
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 Immune Modulation and Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 0 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: stopped early, as of the sponsor's last update on 14 Nov 2019. 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 United States. 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 was stopped early (reason given: Slow/insufficient accrual). 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?
To compare the in vitro and mouse model immune stimulatoryproperties of lysates derived from microbe-specific CDB+ T cellenriched sources. (time frame: There are no definitive time points in this sample collection study). 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 NCT03084614, which also lists 3 linked publications.
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 14 Nov 2019.