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Adjunctive Doxycycline for Central Nervous System Tuberculosis

NCT06446245 · Status: RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 200

Last updated 2025-08-27

No results posted yet for this study

Summary

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.

Conditions

  • Tuberculosis, Meningeal
  • Tuberculosis; Meningitis (Etiology)
  • Tuberculosis, Central Nervous System
  • Tuberculosis; Meningoencephalitis (Etiology)

Interventions

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

Sponsors & Collaborators

  • National Medical Research Council (NMRC), Singapore

    collaborator OTHER_GOV

  • National University Hospital, Singapore

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
PARALLEL

Eligibility

Min Age
21 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-08-21
Primary Completion
2027-11-30
Completion
2027-12-31

Countries

  • Indonesia
  • Malaysia
  • Singapore

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06446245 on ClinicalTrials.gov