NCT06446245RecruitingPhase 2
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
Source: ClinicalTrials.gov · Last updated 1 Jun 2026
Brief summary (registry, in English)
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.
- Status (registry)
- Recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 200 (estimated)
- First submitted
- 28 May 2024
- Start date
- 21 Aug 2025
- Primary completion date
- Nov 2027
- Lead sponsor
- National University Hospital, Singapore
- Diseases
- Tuberculosis
- NCT number
- NCT06446245
What you commit to
- Study type: Interventional · Phase 2
- Planned participants: 200
- From 21 Aug 2025 to the primary completion date, Nov 2027
- 6 sites in 3 countries
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Patients on retinoic acid, neuromuscular blocking agents or pimozide which may increase the risk of drug toxicity.
- 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.
- Enrolment in any other clinical trial involving a systemic drug or intervention involving the CNS.
- Contraindications to the use of steroids.
Other illness
- Active Cancer
- Allergies to tetracyclines
- Autoimmune disease and/or on systemic immunosuppressants.
Other
- Pregnant or breastfeeding
- 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.
Who the study is looking for
- Aged 21 years and above.
- Patients receiving ≤ 7 days of TB treatment or about to start combination TB treatment, including injectable agents, where required.
- Patients with clinical evidence of TB meningitis, as per established diagnostic criteria, defined as either definite, probable or possible CNS-TB:
- "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.
- "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.
- "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.
- Alanine aminotransferase (ALT) level \< 3 times the upper limit of normal.
- 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.
- Lumbar puncture and brain imaging (either computed tomography or magnetic resonance imaging, with or without contrast) is required at baseline for enrolment
Age in the registry: 21 years to - · Sex: All · Does not accept healthy volunteers
Sites (6)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Murni Teguh Memorial Hospital Coordinator of this site? Confirm its status | Medan | Indonesia | Recruiting |
| Universitas Sumatera Utara Coordinator of this site? Confirm its status | Medan | Indonesia | Recruiting |
| Adam Malik Hospital Coordinator of this site? Confirm its status | Medan | Indonesia | Recruiting |
| Sarawak General Hospital Coordinator of this site? Confirm its status | Kuching | Malaysia | Not yet recruiting |
| National University Hospital Coordinator of this site? Confirm its status | Singapore | Singapore | Recruiting |
| Tan Tock Seng Hospital Coordinator of this site? Confirm its status | Singapore | Singapore | Recruiting |
This page is information, not medical advice. Discuss any trial with your doctor.