Efficacy and Safety of Minocycline Add-on in Patients With Neurosyphilis

Study Objective: Neurosyphilis remains a major clinical challenge: despite standard first-line therapy with intravenous penicillin G, as recommended by international and Chinese guidelines, approximately 30% of patients have residual neurological impairment. Minocycline, a tetracycline antibiotic, has both anti-Treponema pallidum activity and independent anti-inflammatory and neuroprotective effects. We therefore designed a prospective, multicenter, randomized, double-blind, placebo-controlled trial to evaluate whether the addition of minocycline to penicillin, as compared with penicillin monotherapy, improves the 6-month rate of favorable neurological outcomes in patients with neurosyphilis. This trial will provide evidence-based evidence for the treatment of neurosyphilis. Inclusion Criteria: 1）Age 18-80 years; 2）Diagnosis of neurosyphilis according to the Guidelines for the Diagnosis and Treatment of Syphilis, Gonorrhea and Genital Chlamydia trachomatis Infection (2020); 3）Cognitive impairment (MMSE score 10-26) or ischemic stroke-like episodes (time from onset to randomization ≤14 days, NIHSS score 1-20); 4）Written informed consent provided by the patient or their legally authorized representative. Intervention: Participants will be randomly assigned ( by chance ) to one of two groups. Group 1 will receive standard intravenous penicillin therapy plus oral minocycline for 28 days. Group 2 will receive standard intravenous penicillin therapy plus oral placebo for 28 days. All participants will receive standard penicillin treatment. Participants and their doctors will not know which group they are in. Follow-up: Participants will be followed for up to 12 months, with five follow-up visits: baseline (before treatment initiation), end of intravenous penicillin treatment (Day 12 ± 2 days), end of minocycline treatment (Day 28 + 2 days), 6 months post-treatment (Month 6 ± 7 days), and 12 months post-treatment (Month 12 ± 7 days). Assessments will include standardized neurological function scales for favorable neurological outcomes, cognitive function, neurological deficits, and activities of daily living; cerebrospinal fluid and serum efficacy marker testing; and brain MRI. Potential Benefits and Risks: Participants may or may not benefit from participating in this study. All participants will receive standard treatment for neurosyphilis. The main risks are complications that may occur during study procedures (such as lumbar puncture, or allergic reactions to penicillin) and possible side effects of minocycline, including dizziness, vestibular side effects, nausea, or skin sensitivity to sunlight. The study team will closely monitor participants for any adverse reactions. Importance of This Study: If minocycline does help improve neurological outcomes, it could become a new treatment option for patients with neurosyphilis, thereby helping to reduce the occurrence of neurological sequelae. The implementation of this study will provide evidence-based evidence for the treatment of neurosyphilis.

Inclusion Criteria: 1. Age 18-80 years; 2. Diagnosis of neurosyphilis according to the Guidelines for the Diagnosis and Treatment of Syphilis, Gonorrhea and Genital Chlamydia trachomatis Infection (2020); 3. Cognitive impairment (MMSE 10-26) or ischemic stroke-like episodes (time from onset to randomization ≤14 days, NIHSS 1-20); 4. Written informed consent provided by the patient or their legally authorized representative. Exclusion Criteria: 1. Allergy or resistance to penicillin or tetracycline antibiotics (including minocycline). 2. Intravenous or intramuscular ceftriaxone for neurosyphilis within 1 month before enrolment (a single intramuscular dose of ceftriaxone for another infection is not exclusionary). 3. Use of tetracycline antibiotics within 1 month before enrolment. 4. Systemic immunosuppression meeting any of the following criteria: use of systemic glucocorticoids (oral or intravenous) within 3 months before enrolment (prednisone-equivalent dose \>10 mg/day for \>2 weeks); current use of immunosuppressants (including but not limited to methotrexate, azathioprine, ciclosporin, mycophenolate mofetil, TNF-α inhibitors, or JAK inhibitors); or discontinuation of immunosuppressants within \