TuberculosisNCT02581579
Study to Evaluate the Tolerability and Immunogenicity of Nyaditum Resae ® Probiotic Administered to Pediatric Population in Contact With Tuberculosis With or Without Latent Tuberculosis Infection
A study testing Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis in people with Tuberculosis, run by Manresana de Micobacteriologia, SL at 3 sites in Spain.
Trial summary
This is a doble-blind, masked, compared with placebo clinical trial in pediatric population in contact with tuberculosis with or without tuberculosis infection. This trial aims to study the effect of the probiotic Nyaditum resae® at the level of specific Treg memory cells eight weeks after the first administration… Read more about this study
- Who is it for?
- Ages 2 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 3 sitesSpain
- Study dates
- 9 Dec 2015to 6 Mar 2019
- Phase
- Interventional
- 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 2 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Child from a study of contact with tuberculosis. Obtaining informed consent from parents / mothers or guardians and, over 12 years, obtaining the consent of the child.
- Child between 2 and 17 years (inclusive) on the day of obtaining informed consent.
- Willingness to fulfill the requirements of the protocol.
Who cannot join
- Active tuberculosis. Enrollment in another clinical trial or study with sanitary product involving invasive techniques.
- Chronic administration of: methotrexate, azathioprine, cyclophosphamide, oral corticosteroids (≥500mg cumulative prednisone dose, or equivalent; inhaled or topical steroids are allowed) and other immunosuppressive therapies / immunomodulatory .
- Administration of blood products or blood derivatives during the 6 months prior to randomization.
- Vaccination in the month prior to randomization. Anticipation of receiving vaccines duration of the study.
- Detection by the researcher lack of knowledge or willingness to participate and fulfill all the requirements of the protocol.
- Any other finding that the investigator's opinion, could jeopardize the performance of the protocol or significantly influence the results or interpretation of the effects of probiotic.
- Known immunodeficiencies. Pregnancy or breastfeeding. Hypersensitivity to mannitol
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Germans Trias I Pujol Hospital
Badalona, Barcelona, 08916
Valle Hebron Hospital
Barcelona, 08035
Hospital Sant Joan de Déu
Esplugues de Llobregat, Barcelona, 08950
About this study
Official title: Pilot Phase I Clinical Trial, Double-blind, Randomized, Placebo Controlled and Masked to Evaluate the Tolerability and Immunogenicity of Nyaditum Resae ® Probiotic Administered to Pediatric Population in Contact With Tuberculosis With or Without Latent Tuberculosis Infection
This is a doble-blind, masked, compared with placebo clinical trial in pediatric population in contact with tuberculosis with or without tuberculosis infection. This trial aims to study the effect of the probiotic Nyaditum resae® at the level of specific Treg memory cells eight weeks after the first administration, and the global tolerability of the treatment.
Nyaditum resae® is a preparation in the form of capsules containing heat-killed environmental mycobacteria Mycobacterium manresensis. The overall objective of the study is the effect of Nyaditum resae® on immunity, which could reduce the risk of developing active tuberculosis.
Read the detailed description
The incidence of tuberculosis is still a problem of the first magnitude. Every year 1.5 million people die; there are 10 million cases of illness and 100 million new infected. The growing problem of multi-resistance is to be added, remaining so prevalent: 700,000 patients, a figure that increases annually with 100,000 people. Prevention of tuberculosis is currently very difficult because it is a disease caused by a bacillus (Mycobacterium tuberculosis) that is transmitted by air: No risk factor for becoming infected has been identified and there is still no prophylactic vaccine that prevents from infection. One of the most characteristic aspects of tuberculosis is that the majority (90-95 %) of people without immunity alterations do not develop the disease after being infected. As for people who do develop the disease, it is still not known why they develop it.
A group of researchers from the Institut Germans Trias i Pujol recently discovered a mechanism that explains this trend. In short, what happens is that certain people create a too strong inflammatory response against tuberculosis bacillus, which ends up creating massive destruction of the tissue that is around the bacillus and brings the characteristic lesion of tuberculosis: tuberculous cavity.
This group of researchers was devising ways to "reeducate" the immune system against the bacillus not make it aggressive. And they did it using two instruments. The first one, an environmental mycobacteria, namely a bacillus of the family of mycobacteria tuberculosis, that usually lives in the water we drink, so that at a greater or lesser extent we already have it in our intestinal flora. The second, inducing a tolerant response, like we do when we eat food. To induce a tolerant response, low and repeated doses of the product make the immune system of the digestive duct "used to" their presence. Thus, when it becomes to find the product, the immune system reacts in a very light and balanced manner, avoiding excessive inflammatory responses. The clearest example is the fact that our immune system "is used" to feed proteins and generates no rejection answers found in the intestinal mucosa.
Hence comes the probiotic Nyaditum resae®, a preparation in the form of capsules, containing a heat-killed Mycobacterium manresensis and thus can generate a cross-immunity with the tuberculosis bacillus. By giving low and repeated dose to generate a tolerant response, which happens when there is an infection by Mycobacterium tuberculosis, so that a balanced immune response is triggered able to reduce the risk of developing active tuberculosis.
Tolerability of Nyaditum resae® has been studied in adults. Next step is to asses its behavior in pediatric population, since is a particularly vulnerable population in countries where there is a high incidence of this disease.
- Conditions
- Tuberculosis
- Being tested
- Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis, Placebo
- Keywords
- Tuberculosis, Tregs, Tolerance, Probiotic, Mycobacteria
- Medical subject headings
- Tuberculosis, Mycobacterium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensisDietary supplement
Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis, 1 capsule per day during 14
PlaceboOther
Placebo, 1 capsule per day during 14
| Study group | Role | What they receive |
|---|---|---|
| Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis | Active comparator | Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis Receives: Dietary Supplement: Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis |
| Placebo | Placebo comparator | MANITOL CAPSULES Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in Specific Treg memory cells at week 1
Measured: From Baseline to Week 8
Proportion of patients presenting adverse events related to study treatment.
Measured: From Baseline to Week 8
Secondary outcomes (2)
Proportion of participants presenting gastrointestinal adverse events related to study treatment.
Measured: Baseline to week 8
Proportion of participants presenting systemic adverse events related to study treatment.
Measured: Baseline to week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2015 (estimated)
- Study start9 Dec 2015
- Primary completion6 Mar 2019
- Study completion6 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manresana de Micobacteriologia, SL
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02581579
- Sponsor's protocol ID
- NYADAPETRICS
- Status last verified
- Dec 2019
- First submitted
- 19 Oct 2015
- Last updated
- 4 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Tukvadze N, Cardona P, Vashakidze S, Shubladze N, Avaliani Z, Vilaplana C, Cardona PJ. Development of the food supplement Nyaditum resae as a new tool to reduce the risk of tuberculosis development. Int J Mycobacteriol. 2016 Dec;5 Suppl 1(Suppl 1):S101-S102. doi: 10.1016/j.ijmyco.2016.09.073. Epub 2016 Nov 14.
PubMed 28043488
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Phase I Clinical Trial, Double-blind, Randomized, Placebo Controlled and Masked to Evaluate the Tolerability and Immunogenicity of Nyaditum Resae ® Probiotic Administered to Pediatric Population in Contact With Tuberculosis With or Without Latent Tuberculosis Infection
- ClinicalTrials.gov ID
- NCT02581579
- Acronym / sponsor ID
- NYADAPETRICS
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, Tregs, Tolerance, Probiotic, Mycobacteria
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Manresana de Micobacteriologia, SLIndustry (pharma, biotech, devices)
- Study start
- 9 Dec 2015 (actual)
- Primary completion
- 6 Mar 2019 (actual)
- Study completion
- 6 Mar 2019 (actual)
- First posted
- 21 Oct 2015 (estimated)
- 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 is a doble-blind, masked, compared with placebo clinical trial in pediatric population in contact with tuberculosis with or without tuberculosis infection. This trial aims to study the effect of the probiotic Nyaditum resae® at the level of specific Treg memory cells eight weeks after the first administration, and the global tolerability of the treatment.
Nyaditum resae® is a preparation in the form of capsules containing heat-killed environmental mycobacteria Mycobacterium manresensis. The overall objective of the study is the effect of Nyaditum resae® on immunity, which could reduce the risk of developing active tuberculosis.
Detailed description
The incidence of tuberculosis is still a problem of the first magnitude. Every year 1.5 million people die; there are 10 million cases of illness and 100 million new infected. The growing problem of multi-resistance is to be added, remaining so prevalent: 700,000 patients, a figure that increases annually with 100,000 people. Prevention of tuberculosis is currently very difficult because it is a disease caused by a bacillus (Mycobacterium tuberculosis) that is transmitted by air: No risk factor for becoming infected has been identified and there is still no prophylactic vaccine that prevents from infection. One of the most characteristic aspects of tuberculosis is that the majority (90-95 %) of people without immunity alterations do not develop the disease after being infected. As for people who do develop the disease, it is still not known why they develop it.
A group of researchers from the Institut Germans Trias i Pujol recently discovered a mechanism that explains this trend. In short, what happens is that certain people create a too strong inflammatory response against tuberculosis bacillus, which ends up creating massive destruction of the tissue that is around the bacillus and brings the characteristic lesion of tuberculosis: tuberculous cavity.
This group of researchers was devising ways to "reeducate" the immune system against the bacillus not make it aggressive. And they did it using two instruments. The first one, an environmental mycobacteria, namely a bacillus of the family of mycobacteria tuberculosis, that usually lives in the water we drink, so that at a greater or lesser extent we already have it in our intestinal flora. The second, inducing a tolerant response, like we do when we eat food. To induce a tolerant response, low and repeated doses of the product make the immune system of the digestive duct "used to" their presence. Thus, when it becomes to find the product, the immune system reacts in a very light and balanced manner, avoiding excessive inflammatory responses. The clearest example is the fact that our immune system "is used" to feed proteins and generates no rejection answers found in the intestinal mucosa.
Hence comes the probiotic Nyaditum resae®, a preparation in the form of capsules, containing a heat-killed Mycobacterium manresensis and thus can generate a cross-immunity with the tuberculosis bacillus. By giving low and repeated dose to generate a tolerant response, which happens when there is an infection by Mycobacterium tuberculosis, so that a balanced immune response is triggered able to reduce the risk of developing active tuberculosis.
Tolerability of Nyaditum resae® has been studied in adults. Next step is to asses its behavior in pediatric population, since is a particularly vulnerable population in countries where there is a high incidence of this disease.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis | Active comparator | Dietary Supplement: Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensisNyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis |
| Placebo | Placebo comparator | Other: PlaceboMANITOL CAPSULES |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Child from a study of contact with tuberculosis. Obtaining informed consent from parents / mothers or guardians and, over 12 years, obtaining the consent of the child.
- Child between 2 and 17 years (inclusive) on the day of obtaining informed consent.
- Willingness to fulfill the requirements of the protocol.
Key exclusion criteria (7 listed)
- Active tuberculosis. Enrollment in another clinical trial or study with sanitary product involving invasive techniques.
- Chronic administration of: methotrexate, azathioprine, cyclophosphamide, oral corticosteroids (≥500mg cumulative prednisone dose, or equivalent; inhaled or topical steroids are allowed) and other immunosuppressive therapies / immunomodulatory .
- Administration of blood products or blood derivatives during the 6 months prior to randomization.
- Vaccination in the month prior to randomization. Anticipation of receiving vaccines duration of the study.
- Detection by the researcher lack of knowledge or willingness to participate and fulfill all the requirements of the protocol.
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 |
|---|---|---|
| Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensisNyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis, 1 capsule per day during 14 | Dietary supplement | Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis |
| PlaceboPlacebo, 1 capsule per day during 14 | Other | Placebo |
Primary outcome
Change from Baseline in Specific Treg memory cells at week 1
Time frame: From Baseline to Week 8
Proportion of patients presenting adverse events related to study treatment.
Time frame: From Baseline to Week 8
2 secondary outcomes
Proportion of participants presenting gastrointestinal adverse events related to study treatment.
Time frame: Baseline to week 8
Proportion of participants presenting systemic adverse events related to study treatment.
Time frame: Baseline to week 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2019.
- Derived from this study: PubMed 28043488Tukvadze N, Cardona P, Vashakidze S, Shubladze N, Avaliani Z, Vilaplana C, Cardona PJ. Development of the food supplement Nyaditum resae as a new tool to reduce the risk of tuberculosis development. Int J Mycobacteriol. 2016 Dec;5 Suppl 1(Suppl 1):S101-S102. doi: 10.1016/j.ijmyco.2016.09.073. Epub 2016 Nov 14.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis in people with Tuberculosis, run by Manresana de Micobacteriologia, SL at 3 sites in Spain.
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 7 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: finished, as of the sponsor's last update on 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change from Baseline in Specific Treg memory cells at week 1 (time frame: From Baseline to Week 8). The study lists 2 primary outcomes in all. 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 NCT02581579, which also lists 1 linked publication.
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 4 Dec 2019.