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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

Adjunctive Doxycycline for Central Nervous System Tuberculosis

DIRECT: Doxycycline Adjunctive Therapy to Reduce Excess Mortality and Complications From Central Nervous System Tuberculosis - Phase II Randomized Clinical Trial

Adjunctive Doxycycline for Central Nervous System Tuberculosis (NCT06446245) is a Phase 2 interventional studying Tuberculosis, Meningeal and Tuberculosis; Meningitis (Etiology), sponsored by National University Hospital, Singapore. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

Although tuberculosis is now considered a treatable disease, central nervous system tuberculosis (CNS-TB) when managed with the current standard-of-care (SOC), still has mortality rates ranging from 30-50% even in tertiary hospital centers. At present, the SOC for the management of CNS-TB is anti-tuberculous therapy with adjunctive corticosteroids. In CNS-TB, the activity of pathogenic host matrix metalloproteinases (MMPs) is unopposed to tissue inhibitors of metalloproteinases (TIMPs), resulting in a matrix-degrading phenotype which may drive worse outcomes in CNS-TB. In a prior established CNS-TB murine model, the investigators have demonstrated that adjunctive MMP inhibition using doxycycline, a widely available and cheap drug, in addition to standard TB treatment, compared with standard TB treatment alone, improved murine survival (Manuscript in preparation). The investigators previously showed that in humans with pulmonary TB, doxycycline with anti-TB treatment is safe, accelerates the resolution of inflammation, and suppresses systemic and respiratory MMPs. Hence, the investigators are now ideally positioned to determine if adjunctive doxycycline in patients with CNS-TB can improve clinical outcomes. The investigators will perform a Phase 2 double-blind randomized-controlled trial (RCT) of adjunctive doxycycline versus placebo with standard TB treatment and steroids for 8 weeks, with the primary outcome of 8-week mortality or severe neurological deficits.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Tuberculosis, Meningeal and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 200 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Tuberculosis, Meningeal subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Aged 21 years and above. 2. Patients receiving ≤ 7 days of TB treatment or about to start combination TB treatment, including injectable agents, where required. 3. Patients with clinical evidence of TB meningitis, as per established diagnostic criteria, defined as either definite, probable or possible CNS-TB: 1. "Definite" CNS-TB would be defined if acid-fast bacilli (AFB) or a positive nucleic acid amplification test for M. tuberculosis in the cerebrospinal fluid of patients. 2. "Probable" CNS-TB would be defined if the patient exhibit one or more of the following: suspected pulmonary tuberculosis on chest radiography, acid-fast bacilli found in any specimen other than the cerebrospinal fluid or clinical evidence of other extrapulmonary tuberculosis. 3. "Possible" CNS-TB would be defined if the patients exhibit at least four of the following: a history of tuberculosis, predominance of lymphocytes in the cerebrospinal fluid, a duration of illness of more than five days, a ratio of cerebrospinal fluid glucose to plasma glucose of less than 0.5, altered consciousness, yellow cerebrospinal fluid, or focal neurologic signs. 4. Alanine aminotransferase (ALT) level \< 3 times the upper limit of normal. 5. Able to provide willing to sign a consent form. If the patient has no mental capacity to give consent, then consent may be provided for by the patient's next of kin. 6. Lumbar puncture and brain imaging (either computed tomography or magnetic resonance imaging, with or without contrast) is required at baseline for enrolment Who Should NOT Join This Trial: 1. Active Cancer 2. Pregnant or breastfeeding 3. Allergies to tetracyclines 4. Patients on retinoic acid, neuromuscular blocking agents or pimozide which may increase the risk of drug toxicity. 5. autoimmune conditions (where your immune system attacks your own body) and/or on systemic immunosuppressants. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Aged 21 years and above. 2. Patients receiving ≤ 7 days of TB treatment or about to start combination TB treatment, including injectable agents, where required. 3. Patients with clinical evidence of TB meningitis, as per established diagnostic criteria, defined as either definite, probable or possible CNS-TB: 1. "Definite" CNS-TB would be defined if acid-fast bacilli (AFB) or a positive nucleic acid amplification test for M. tuberculosis in the cerebrospinal fluid of patients. 2. "Probable" CNS-TB would be defined if the patient exhibit one or more of the following: suspected pulmonary tuberculosis on chest radiography, acid-fast bacilli found in any specimen other than the cerebrospinal fluid or clinical evidence of other extrapulmonary tuberculosis. 3. "Possible" CNS-TB would be defined if the patients exhibit at least four of the following: a history of tuberculosis, predominance of lymphocytes in the cerebrospinal fluid, a duration of illness of more than five days, a ratio of cerebrospinal fluid glucose to plasma glucose of less than 0.5, altered consciousness, yellow cerebrospinal fluid, or focal neurologic signs. 4. Alanine aminotransferase (ALT) level \< 3 times the upper limit of normal. 5. Able to provide informed consent. If the patient has no mental capacity to give consent, then consent may be provided for by the patient's next of kin. 6. Lumbar puncture and brain imaging (either computed tomography or magnetic resonance imaging, with or without contrast) is required at baseline for enrolment Exclusion Criteria: 1. Active Cancer 2. Pregnant or breastfeeding 3. Allergies to tetracyclines 4. Patients on retinoic acid, neuromuscular blocking agents or pimozide which may increase the risk of drug toxicity. 5. Autoimmune disease and/or on systemic immunosuppressants. 6. Use of any investigational or non-registered drug, vaccine or medical device other than the study drug within 182 days preceding dosing of the study drug or planned use during the study period. 7. Enrolment in any other clinical trial involving a systemic drug or intervention involving the CNS. 8. Contraindications to the use of steroids. 9. Investigators' assessment of lack of willingness to participate and comply with all requirements including follow-up of the protocol or identification of any factor presumed to significantly increase the participant's risk of suffering an adverse outcome.

Treatments Being Tested

DRUG

Doxycycline

adjunctive doxycycline to standard anti-tuberculous treatment and corticosteroid therapy

DRUG

Placebo

Placebo

DRUG

Anti Tuberculosis Drug

Standard anti-tuberculous therapy

DRUG

Adjunctive corticosteroid

Adjunctive corticosteroids to be dosed at 0.4mg/kg/day of dexamethasone or equivalent for week 1, then 0.3mg/kg/day for week 2, 0.2mg/kg/day for week 3, 0.1mg/kg/day for week 4, then tapered to stop over the next 4 weeks. Other forms of corticosteroids are also acceptable eg. hydrocortisone, methylprednisolone at the equivalent dosage

Locations (5)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Adam Malik Hospital
Medan, Indonesia
Universitas Sumatera Utara
Medan, Indonesia
Sarawak General Hospital
Kuching, Sarawak, Malaysia
National University Hospital
Singapore, Singapore
Tan Tock Seng Hospital
Singapore, Singapore

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06446245), the sponsor (National University Hospital, Singapore), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06446245 clinical trial studying?

Although tuberculosis is now considered a treatable disease, central nervous system tuberculosis (CNS-TB) when managed with the current standard-of-care (SOC), still has mortality rates ranging from 30-50% even in tertiary hospital centers. At present, the SOC for the management of CNS-TB is anti-tuberculous therapy with adjunctive corticosteroids. In CNS-TB, the activity of pathogenic host matrix metalloproteinases (MMPs) is unopposed to tissue inhibitors of metalloproteinases (TIMPs), resulting in a matrix-degrading phenotype which may drive worse outcomes in CNS-TB. In a prior established C… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06446245?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06446245?

Contact information for this trial may be available directly on the ClinicalTrials.gov record. Click "View on ClinicalTrials.gov" in the sidebar for the official source. Always discuss any potential trial with your doctor before contacting the study site.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06446245. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06446245. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.