Adjunctive Doxycycline for Central Nervous System Tuberculosis

Launched by NATIONAL UNIVERSITY HOSPITAL, SINGAPORE · Jun 5, 2024

Keywords

ClinConnect Summary

This clinical trial is studying whether adding a medication called doxycycline to the standard treatment for central nervous system tuberculosis (CNS-TB) can improve patient outcomes. CNS-TB is a serious form of tuberculosis that affects the brain and spine, and even with current treatments, many patients still face high risks of severe illness or death. The researchers believe that doxycycline may help reduce inflammation and improve recovery when used alongside the usual anti-tuberculosis medications and steroids.

To be eligible for this trial, participants must be at least 21 years old and either starting or have recently begun treatment for tuberculosis. They must have signs of meningitis, which is an infection of the protective membranes covering the brain and spinal cord. Participants will receive either doxycycline or a placebo (a harmless pill that looks the same) along with standard therapy for 8 weeks. Throughout the trial, they will be monitored for any serious health issues, such as severe neurological problems or death. Importantly, the trial is not yet recruiting participants, but it aims to help improve treatment options for those affected by this challenging condition.

Gender

ALL

Eligibility criteria

• 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.