Adjunctive Doxycycline for Central Nervous System Tuberculosis

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.

NCT Number	NCT06446245
Lead Sponsor	National University Hospital, Singapore Collaborators: National Medical Research Council (NMRC), Singapore
Conditions	Tuberculosis, Meningeal, Tuberculosis; Meningitis (Etiology), Tuberculosis, Central Nervous System, Tuberculosis; Meningoencephalitis (Etiology)
Enrollment	200 participants
Start Date	2025-08-21
Primary Completion	2027-11 (estimated)
Study Completion	2027-12 (estimated)
Updated on ClinicalTrials.gov	2026-06-01