TuberculosisNCT03851159
Nyaditum Resae® as a Co-adjuvant During Treatment for Active Pulmonary Tuberculosis and Its Impact on the Gut Microbiota
A study testing Nyaditum resae® and Mannitol in people with Tuberculosis, run by University of Stellenbosch at 2 sites in South Africa.
Trial summary
This will be the first study to evaluate the use of Nyaditum resae® as a potential agent for reducing antibiotic-associated gut dysbiosis in patients with drug-susceptible TB, and potentially improving clinical and microbiological markers of outcome Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Nyaditum resae® and Mannitol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 2 sitesSouth Africa
- Study dates
- 10 May 2019to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-65 years
- New cases
- Sputum Xpert Ultra (Xpert) positive for Mycobacterium tuberculosis
- Have not initiated TB treatment
- If HIV-positive, are stable on antiretroviral therapy
Who cannot join
- Resistance to any of the first-line drugs (Xpert rifampicin-resistant)
- Previous TB
- Diabetes mellitus
- Taking immunomodulatory drugs (e.g. cancer chemotherapy, tumour necrosis factor (TNF) inhibitors or other anti-inflammatory medication, phosphodiesterase inhibitors, corticosteroids within the past 6 months, and cholesterol-lowering drugs)
- Pregnant or lactating women
- Chronic hepatitis
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Scottsdene Clinic
Cape Town, Western Cape, 7570
Wallacedene Clinic
Cape Town, Western Cape, 7570
About this study
Official title: Nyaditum Resae® (a Food Supplement) as a Co-adjuvant During First-line Treatment for Active Pulmonary Tuberculosis and Its Impact on the Gut Microbiota - a Pilot Double-blind Randomised Controlled Trial
This will be the first study to evaluate the use of Nyaditum resae® as a potential agent for reducing antibiotic-associated gut dysbiosis in patients with drug-susceptible TB, and potentially improving clinical and microbiological markers of outcome
Read the detailed description
About one tenth of the 1.7 billion individuals infected with Mycobacterium tuberculosis (Mtb) will progress to active tuberculosis (TB). This probability increases in people with human immunodeficiency virus (HIV) and other risk co-morbidities such as malnutrition, diabetes and substance abuse. Chronic microbial colonisation with unrelated bacteria are associated with TB pathogenesis (e.g., mice colonised with Helicobacter hepaticus exhibit poor control of TB), indicating that the gut microbiota may modulate progression to active TB. Furthermore, first-line TB treatment (Isoniazid, Rifampicin, Ethambutol, Pyrazinamide; HREZ) depletes gut commensal bacteria (Ruminococcus, Coprococcus and Bifidobacterium) with immunomodulatory roles [interleukin (IL)-1, interferon (IFN)-γ and Th17 responses, respectively).
Recent work identified heat-killed Mycobacterium manresensis (hkMm), a harmless member of the fortuitum complex naturally found in drinking water, as a promising candidate for reducing the risk of active TB. Mtb-infected mice treated with hkMm had significantly reduced lung pathology (fewer and smaller lesions,) bacillary load and proinflammatory cytokines (TNF-α, IFN-γ, IL-6, and IL-17) compared to untreated control mice, and in mice receiving hkMm with HREZ, survival rates were significantly increased. Moreover, mice treated with hkMm had increased microbial diversity and an altered gut microbial composition relative to untreated mice. This could prove beneficial for TB patients during prolonged antibiotic treatment as supplementation with hkMm may help protect gut microbiota, and potentially improve clinical outcome.
In individuals with and without latent M. tuberculosis infection, two weeks of daily oral doses of Nyaditum resae® (a preparation of hkMm approved as a food supplement by Manremyc) demonstrated enhanced effector and memory specific regulatory T-cell responses. Similar clinical trials with Nyaditum resae® are currently being done in paediatrics (NCT02581579) and close contacts of active TB cases in Tbilisi, Georgia (NCT02897180; 2017-2023). The probiotic is also being registered as a food supplement in several countries.
In the proposed study, the efficacy of Nyaditum resae® in reducing antibiotic-associated gut dysbiosis and disease progression in patients with active TB will be tested. To do this, the investigators will assess changes in the microbiota during treatment (with or without Nyaditum resae® supplementation) and attempt to identify genera associated with a favourable or unfavourable treatment outcome in TB patients.
- Conditions
- Tuberculosis
- Being tested
- Nyaditum resae®, Mannitol
- Keywords
- Microbiome
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nyaditum resae®Dietary supplement
Heat-killed Mycobacterium manresensis
MannitolOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| No Intervention: HIV-negative | Placebo comparator | HIV-negative patients are selected to receive the placebo for the first two weeks of first-line TB treatment. Receives: Other: Mannitol |
| Intervention: HIV- | Experimental | HIV-negative patients are selected to receive the food supplement for the first two weeks of first-line TB treatment. Receives: Dietary Supplement: Nyaditum resae® |
| No Intervention: HIV+ | Placebo comparator | HIV-positive patients are selected to receive the placebo for the first two weeks of first-line TB treatment. Receives: Other: Mannitol |
| Intervention: HIV+: | Experimental | HIV-positive patients are selected to receive the food supplement for the first two weeks of first-line TB treatment. Receives: Dietary Supplement: Nyaditum resae® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gut microbiome composition in placebo versus experimental arm
Gut microbial composition determined by next-generation sequencing of bacterial DNA in stool
Measured: Up to 18 months
Secondary outcomes (2)
Cytokine and cluster of differentiation (CD)4+ T-cell response in placebo versus experimental arm
Cytokines responses profiled using commercial human cytokine panel, and T-cell responses characterised by flow cytometry on isolated peripheral blood mononuclear cells
Measured: Up to 18 months
Time to sputum conversion and reduction in bacillary load
Culture used to assess sputum conversion and bacillary load
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2019
- Study start10 May 2019
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Stellenbosch
- Sponsor type
- University, hospital or other
- Collaborators
- Fundació Institut Germans Trias i Pujol
- Responsible party
- Principal investigator, Grant Theron, University of Stellenbosch
- Investigators
- Grant Theron, PHD, Principal investigator, University of Stellenbosch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03851159
- Sponsor's protocol ID
- N14_10_136
- Status last verified
- May 2026
- First submitted
- 19 Feb 2019
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nyaditum Resae® (a Food Supplement) as a Co-adjuvant During First-line Treatment for Active Pulmonary Tuberculosis and Its Impact on the Gut Microbiota - a Pilot Double-blind Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT03851159
- Acronym / sponsor ID
- N14_10_136
- Conditions
- Tuberculosis
- Keywords
- Microbiome
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of StellenboschUniversity, hospital or other
- Collaborators
- Fundació Institut Germans Trias i Pujol
- Study start
- 10 May 2019 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 22 Feb 2019 (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 will be the first study to evaluate the use of Nyaditum resae® as a potential agent for reducing antibiotic-associated gut dysbiosis in patients with drug-susceptible TB, and potentially improving clinical and microbiological markers of outcome
Detailed description
About one tenth of the 1.7 billion individuals infected with Mycobacterium tuberculosis (Mtb) will progress to active tuberculosis (TB). This probability increases in people with human immunodeficiency virus (HIV) and other risk co-morbidities such as malnutrition, diabetes and substance abuse. Chronic microbial colonisation with unrelated bacteria are associated with TB pathogenesis (e.g., mice colonised with Helicobacter hepaticus exhibit poor control of TB), indicating that the gut microbiota may modulate progression to active TB. Furthermore, first-line TB treatment (Isoniazid, Rifampicin, Ethambutol, Pyrazinamide; HREZ) depletes gut commensal bacteria (Ruminococcus, Coprococcus and Bifidobacterium) with immunomodulatory roles [interleukin (IL)-1, interferon (IFN)-γ and Th17 responses, respectively).
Recent work identified heat-killed Mycobacterium manresensis (hkMm), a harmless member of the fortuitum complex naturally found in drinking water, as a promising candidate for reducing the risk of active TB. Mtb-infected mice treated with hkMm had significantly reduced lung pathology (fewer and smaller lesions,) bacillary load and proinflammatory cytokines (TNF-α, IFN-γ, IL-6, and IL-17) compared to untreated control mice, and in mice receiving hkMm with HREZ, survival rates were significantly increased. Moreover, mice treated with hkMm had increased microbial diversity and an altered gut microbial composition relative to untreated mice. This could prove beneficial for TB patients during prolonged antibiotic treatment as supplementation with hkMm may help protect gut microbiota, and potentially improve clinical outcome.
In individuals with and without latent M. tuberculosis infection, two weeks of daily oral doses of Nyaditum resae® (a preparation of hkMm approved as a food supplement by Manremyc) demonstrated enhanced effector and memory specific regulatory T-cell responses. Similar clinical trials with Nyaditum resae® are currently being done in paediatrics (NCT02581579) and close contacts of active TB cases in Tbilisi, Georgia (NCT02897180; 2017-2023). The probiotic is also being registered as a food supplement in several countries.
In the proposed study, the efficacy of Nyaditum resae® in reducing antibiotic-associated gut dysbiosis and disease progression in patients with active TB will be tested. To do this, the investigators will assess changes in the microbiota during treatment (with or without Nyaditum resae® supplementation) and attempt to identify genera associated with a favourable or unfavourable treatment outcome in TB patients.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| No Intervention: HIV-negative | Placebo comparator | Other: MannitolHIV-negative patients are selected to receive the placebo for the first two weeks of first-line TB treatment. |
| Intervention: HIV- | Experimental | Dietary Supplement: Nyaditum resae®HIV-negative patients are selected to receive the food supplement for the first two weeks of first-line TB treatment. |
| No Intervention: HIV+ | Placebo comparator | Other: MannitolHIV-positive patients are selected to receive the placebo for the first two weeks of first-line TB treatment. |
| Intervention: HIV+: | Experimental | Dietary Supplement: Nyaditum resae®HIV-positive patients are selected to receive the food supplement for the first two weeks of first-line TB treatment. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18-65 years
- New cases
- Sputum Xpert Ultra (Xpert) positive for Mycobacterium tuberculosis
- Have not initiated TB treatment
- If HIV-positive, are stable on antiretroviral therapy
Key exclusion criteria (6 listed)
- Resistance to any of the first-line drugs (Xpert rifampicin-resistant)
- Previous TB
- Diabetes mellitus
- Taking immunomodulatory drugs (e.g. cancer chemotherapy, tumour necrosis factor (TNF) inhibitors or other anti-inflammatory medication, phosphodiesterase inhibitors, corticosteroids within the past 6 months, and cholesterol-lowering drugs)
- Pregnant or lactating women
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®Heat-killed Mycobacterium manresensis | Dietary supplement | Intervention: HIV+:, Intervention: HIV- |
| MannitolPlacebo | Other | No Intervention: HIV+, No Intervention: HIV-negative |
Primary outcome
Gut microbiome composition in placebo versus experimental arm
Time frame: Up to 18 months
Gut microbial composition determined by next-generation sequencing of bacterial DNA in stool
2 secondary outcomes
Cytokine and cluster of differentiation (CD)4+ T-cell response in placebo versus experimental arm
Time frame: Up to 18 months
Time to sputum conversion and reduction in bacillary load
Time frame: Up to 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
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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.
Grant Theron, PHD principal investigator
University of Stellenbosch
2 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® and Mannitol in people with Tuberculosis, run by University of Stellenbosch at 2 sites in South Africa.
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 5 inclusion and 6 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: under way, not looking for participants, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. 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?
This study is still under way. Results are not available in the source record yet.
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?
Gut microbiome composition in placebo versus experimental arm (time frame: Up to 18 months). 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 5 May 2026.