NeurosyphilisPhase 3MIN-ADDNCT07904533
Efficacy and Safety of Minocycline Add-on in Patients With Neurosyphilis
A Phase 3 study testing Minocycline and Aqueous crystalline penicillin G in people with Neurosyphilis, run by Beijing Ditan Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neurosyphilis
- What is being tested?
- Minocycline and Aqueous crystalline penicillin G
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 778 participants
- Where
- 1 siteChina
- Study dates
- 15 Nov 2026to 22 Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-80 years;
- Diagnosis of neurosyphilis according to the Guidelines for the Diagnosis and Treatment of Syphilis, Gonorrhea and Genital Chlamydia trachomatis Infection (2020);
- Cognitive impairment (MMSE 10-26) or ischemic stroke-like episodes (time from onset to randomization ≤14 days, NIHSS 1-20);
- Written informed consent provided by the patient or their legally authorized representative.
Who cannot join
- Allergy or resistance to penicillin or tetracycline antibiotics (including minocycline).
- Intravenous or intramuscular ceftriaxone for neurosyphilis within 1 month before enrolment (a single intramuscular dose of ceftriaxone for another infection is not exclusionary).
- Use of tetracycline antibiotics within 1 month before enrolment.
- 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 <4 weeks or <5 half-lives (whichever is longer).
- Pre-morbid modified Rankin Scale (mRS) score >2.
- History of psychiatric disorders (e.g., schizophrenia or depression).
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- HIV infection meeting any of the following criteria: screening CD4+ T-cell count <200 cells/μL; or virological failure, defined as receiving antiretroviral therapy for ≥6 months with two consecutive plasma HIV RNA levels >200 copies/mL (measured 2-4 weeks apart).
- Cognitive impairment from other causes (e.g., Alzheimer's disease, frontotemporal dementia, thyroid dysfunction, folate/vitamin B12 deficiency, or alcohol use disorder).
- Ischaemic stroke clearly attributable to other aetiologies.
- Active co-infection with central nervous system opportunistic pathogens (e.g., tuberculous meningitis, cryptococcal meningitis, toxoplasmic encephalitis, or cytomegalovirus encephalitis).
- Other central nervous system or systemic diseases causing abnormal cerebrospinal fluid parameters (including but not limited to autoimmune encephalitis, multiple sclerosis, central nervous system tumours, systemic lupus erythematosus, antiphospholipid syndrome, sarcoidosis, or systemic vasculitis).
- Severe renal impairment (serum creatinine >3.0 mg/dL [265.2 μmol/L], glomerular filtration rate <30 mL/min/1.73 m², or on dialysis) or severe hepatic impairment (ALT or AST >3 × upper limit of normal).
- Severe underlying comorbidities with an expected life expectancy of <1 year.
- Pregnancy or lactation; or women of childbearing potential with a negative pregnancy test who decline to use effective contraception.
- Current participation in another investigational drug or device trial.
- Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation or unable to comply with the protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Beijing Ditan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100015
Xia Meng, MD, +86-13811821377, mengxia45@163.com
Wen Tian, MD, +86-18900961385, 18900961385@163.com
About this study
Official title: Efficacy and Safety of Minocycline Add-on in Patients With Neurosyphilis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial （MIN-ADD）
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.
- Conditions
- Neurosyphilis
- Being tested
- Minocycline, Minocycline placebo, Aqueous crystalline penicillin G
- Keywords
- Minocycline, Penicillin G, Randomized Controlled Trial, Neurological Outcomes, Treatment, Adjunctive Therapy
- Medical subject headings
- Neurosyphilis, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Administered orally. Loading dose of 200 mg on Day 1, followed by 100 mg every 12 hours for 28 days. Given only to participants in the Experimental Group.
Minocycline placeboDrug
Oral matching placebo to minocycline. Loading dose of 200 mg on Day 1, followed by 100 mg every 12 hours for 28 days. Given only to participants in the Control Group.
Aqueous crystalline penicillin GDrug
Administered intravenously at 18-24 million units per day for 10-14 days. Given to all participants in both arms.
| Study group | Role | What they receive |
|---|---|---|
| Penicillin plus Minocycline | Experimental | Participants will receive standard intravenous aqueous crystalline penicillin G (18-24 million units/day for 10-14 days) plus oral minocycline (200 mg loading dose on Day 1, followed by 100 mg every 12 hours) for 28 days. Receives: Drug: Minocycline; Drug: Aqueous crystalline penicillin G |
| Penicillin plus Placebo | Placebo comparator | Participants will receive standard intravenous aqueous crystalline penicillin G (18-24 million units/day for 10-14 days) plus oral matching minocycline placebo (200 mg loading dose on Day 1, followed by 100 mg every 12 hours) for 28 days. Receives: Drug: Minocycline placebo; Drug: Aqueous crystalline penicillin G |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with favorable neurological outcomes at 6 months
Unit of measure: Percentage (%). A favorable neurological outcome is defined as meeting both of the following criteria: (1) a modified Rankin Scale score of 0 to 2, AND (2) at least one of the following: an improvement in the Mini-Mental State Examination score of ≥2 points from baseline, or a Mini-Mental State Examination score of >26. The Mini-Mental State Examination score ranges from 0 to 30, with higher scores indicating better cognitive function. The modified Rankin Scale score ranges from 0 to 6, with higher scores indicating worse disability.
Measured: At 6 months post-treatment
Secondary outcomes (18)
Proportion of participants with normal cerebrospinal fluid (CSF) white blood cell counts
Unit of measure: Percentage (%). The proportion of participants with normal cerebrospinal fluid (CSF) white blood cell counts (≤5 cells/μL; or ≤20 cells/μL for participants with HIV) at 6 months, as measured by CSF analysis.
Measured: At 6 months post-treatment
Proportion of participants with normal cerebrospinal fluid (CSF) protein levels
Unit of measure: Percentage (%). The proportion of participants with normal cerebrospinal fluid (CSF) protein levels (<500 mg/L) at 6 months post-treatment, as measured by CSF biochemical analysis.
Measured: At 6 months post-treatment
Proportion of participants with a ≥4-fold decline or seroreversion in cerebrospinal fluid (CSF) non-treponemal antibody titers
Unit of measure: Percentage (%). The proportion of participants with a ≥4-fold decline or seroreversion in cerebrospinal fluid (CSF) non-treponemal antibody titers. Titers are measured by Venereal Disease Research Laboratory (VDRL), toluidine red unheated serum test (TRUST), or rapid plasma reagin (RPR) tests on CSF samples. Notably, titer assessments must use the same assay method as the baseline measurement; results from different methods are not comparable.
Measured: At 6 months post-treatment
Proportion of participants with a ≥4-fold decline or seroreversion in serum non-treponemal antibody titers
Unit of measure: Percentage (%). The proportion of participants with a ≥4-fold decline or seroreversion in serum non-treponemal antibody titers, measured by toluidine red unheated serum test (TRUST) or rapid plasma reagin (RPR) tests on serum samples. Notably, titer assessments must use the same assay method as the baseline measurement; results from different methods are not comparable.
Measured: At 6 months post-treatment
Proportion of participants with a modified Rankin Scale (mRS) score of 0 to 2
Unit of measure: Percentage (%). The proportion of participants with a modified Rankin Scale (mRS) score of 0 to 2 at 6 months post-treatment. The mRS is a 7-point scale ranging from 0 to 6, where a score of 0 indicates no symptoms and a score of 6 indicates death. A score of 0 to 2 indicates functional independence (a favorable outcome). Higher scores indicate worse disability.
Measured: At 6 months post-treatment
Proportion of participants with a ≥2-point improvement or a score >26 in the Mini-Mental State Examination
Unit of measure: Percentage (%). The proportion of participants meeting at least one of the following criteria at 6 months: (1) an improvement of ≥2 points from baseline in the Mini-Mental State Examination (MMSE) score, or (2) an MMSE score of >26. The MMSE is a 30-point questionnaire ranging from 0 to 30, where higher scores indicate better cognitive function.
Measured: At 6 months post-treatment
Change from baseline in the modified Rankin Scale (mRS) score at 6 months
Unit of measure: Points. The change in the modified Rankin Scale (mRS) score from baseline to 6 months post-treatment (calculated as the 6-month score minus the baseline score). The mRS is a 7-point scale ranging from 0 to 6, where a score of 0 indicates no symptoms and 6 indicates death. Higher scores indicate worse disability. A negative value indicates an improvement (reduction in disability) from baseline.
Measured: At 6 months post-treatment
Change from baseline in the Mini-Mental State Examination (MMSE) score at 6 months
Unit of measure: Points. The change in the MMSE score from baseline to 6 months post-treatment (calculated as the 6-month score minus the baseline score). The MMSE ranges from 0 to 30, with higher scores indicating better cognitive function. A negative value indicates cognitive decline.
Measured: At 6 months post-treatment
Change from baseline in the Montreal Cognitive Assessment (MoCA) Beijing version score at 6 months
Unit of measure: Points. The change in the Montreal Cognitive Assessment (MoCA) Beijing version score from baseline to 6 months post-treatment (calculated as the 6-month score minus the baseline score). The MoCA Beijing version ranges from 0 to 30, with higher scores indicating better cognitive function. A negative value indicates cognitive decline.
Measured: At 6 months post-treatment
Change from baseline in the National Institutes of Health Stroke Scale (NIHSS) score at 6 months
Unit of measure: Points. The change in the NIHSS score from baseline to 6 months post-treatment (calculated as the 6-month score minus the baseline score). The NIHSS ranges from 0 to 42, with higher scores indicating more severe neurological deficits. A negative value indicates neurological improvement.
Measured: At 6 months post-treatment
Change from baseline in the Lawton Activities of Daily Living Scale (Chinese 14-item revised version) score at 6 months
Unit of measure: Points. The change in the Lawton Activities of Daily Living Scale score from baseline to 6 months post-treatment (calculated as the 6-month score minus the baseline score). Based on the framework of Lawton \& Brody (1969), this 14-item Chinese revised version includes 6 basic ADL and 8 instrumental ADL items. Each item is scored from 1 to 4, yielding a total score ranging from 14 to 56, with higher scores indicating worse function. A negative value indicates an improvement in daily function.
Measured: At 6 months post-treatment
Change from baseline in the Beck Depression Inventory-II (BDI-II) score at 6 months
Unit of measure: Points. The change in the BDI-II score from baseline to 6 months post-treatment (calculated as the 6-month score minus the baseline score). The BDI-II ranges from 0 to 63, with higher scores indicating more severe depressive symptoms. A negative value indicates an improvement in depressive symptoms.
Measured: At 6 months post-treatment
Change from baseline in the Neuropsychiatric Inventory (NPI) score at 6 months
Unit of measure: Points. The change in the NPI score from baseline to 6 months post-treatment (calculated as the 6-month score minus the baseline score). The NPI total score ranges from 0 to 144, with higher scores indicating more severe neuropsychiatric symptoms. A negative value indicates an improvement in neuropsychiatric symptoms.
Measured: At 6 months post-treatment
Change from baseline in the Global Cortical Atrophy (GCA) total score at 6 months
Unit of measure: Points. The change in the Global Cortical Atrophy (GCA) total score from baseline to 6 months post-treatment (calculated as the 6-month score minus the baseline score). The GCA scale assesses cortical atrophy on cranial MRI by evaluating three regions: the frontal, parietal, and temporal lobes. Each of the three regions is scored from 0 to 3 (where 0 = no atrophy and 3 = severe atrophy). The total GCA score is the sum of the scores for these three regions, ranging from 0 to 9, with higher scores indicating more severe brain atrophy. A positive value indicates progression of brain atrophy.
Measured: At 6 months post-treatment
Change from baseline in total brain lesion volume on Magnetic Resonance Imaging (MRI) at 6 months
Unit of measure: Cubic millimeters (mm³). The change in the total volume of brain lesions from baseline to 6 months post-treatment (calculated as the 6-month volume minus the baseline volume). The lesion volume is measured using T2-weighted or FLAIR sequences on cranial MRI. A positive value indicates an increase in lesion volume (worsening).
Measured: At 6 months post-treatment
All-cause mortality at 6 months
Unit of measure: Count (number of participants). The number of participants who died from any cause during the 6-month period post-treatment.
Measured: Up to 6 months post-treatment
Number of participants with adverse events (AEs) at 6 months
Unit of measure: Count (number of participants). The number of participants who experienced at least one adverse event (AE) from baseline to 6 months post-treatment. Adverse events are assessed and graded according to standard clinical safety criteria.
Measured: Up to 6 months post-treatment
Number of participants with serious adverse events (SAEs) at 6 months
Unit of measure: Count (number of participants). The number of participants who experienced at least one serious adverse event (SAE) from baseline to 6 months post-treatment. SAEs are assessed and graded according to standard clinical safety criteria.
Measured: Up to 6 months post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2026
- Study start15 Nov 2026 (estimated)
- Primary completion22 May 2028 (estimated)
- Study completion22 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for NeurosyphilisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomly assigned in a 1:1 ratio to either the experimental group (intravenous penicillin plus oral minocycline) or the control group (intravenous penicillin plus oral placebo). Both groups receive standard intravenous penicillin therapy for 10-14 days, followed by their respective oral study medication (minocycline or placebo) for 28 days.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 778 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Ditan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xia Meng, Beijing Ditan Hospital
- Investigators
- Xia Meng, MD, Principal investigator, Beijing Ditan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07904533
- Sponsor's protocol ID
- DTEC-KY2026-117-03
- Acronym
- MIN-ADD
- Status last verified
- Oct 2026
- First submitted
- 19 Oct 2026
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared. The data collected in this study will be used solely by the study investigators for the purposes outlined in this protocol.
Publications
Million M, Thuny F, Richet H, Raoult D. Long-term outcome of Q fever endocarditis: a 26-year personal survey. Lancet Infect Dis. 2010 Aug;10(8):527-35. doi: 10.1016/S1473-3099(10)70135-3. Epub 2010 Jul 14.
PubMed 20637694Bollenbach T. Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution. Curr Opin Microbiol. 2015 Oct;27:1-9. doi: 10.1016/j.mib.2015.05.008. Epub 2015 Jun 1.
PubMed 26042389Ishak A, Mazonakis N, Spernovasilis N, Akinosoglou K, Tsioutis C. Bactericidal versus bacteriostatic antibacterials: clinical significance, differences and synergistic potential in clinical practice. J Antimicrob Chemother. 2025 Jan 3;80(1):1-17. doi: 10.1093/jac/dkae380.
PubMed 39471409Shao LL, Guo R, Shi WJ, Liu YJ, Feng B, Han L, Liu QZ. Could lengthening minocycline therapy better treat early syphilis? Medicine (Baltimore). 2016 Dec;95(52):e5773. doi: 10.1097/MD.0000000000005773.
PubMed 28033297Lu Y, Guan L, Wu J, Yang Q, Zhang M, Zhou D, Yang H, Pan Y, Wang L, Qiu B, Liu C, Wang Y, Yang Y, Zhou X, Qu H, Liao X, Liu L, Zhao X, Bath PM, Johnston SC, Amarenco P, Turc G, Shi FD, Wang Y, Wang Y; EMPHASIS Investigators. Efficacy and safety of minocycline in patients with acute ischaemic stroke (EMPHASIS): a multicentre, double-blind, randomised controlled trial. Lancet. 2026 Feb 14;407(10529):679-688. doi: 10.1016/S0140-6736(25)01862-8. Epub 2026 Jan 30.
PubMed 41628627Zhang L, Zhao J. Profile of minocycline and its potential in the treatment of schizophrenia. Neuropsychiatr Dis Treat. 2014 Jun 17;10:1103-11. doi: 10.2147/NDT.S64236. eCollection 2014.
PubMed 24971013Mert T, Sahin E, Yaman S, Sahin M. Effects of immune cell-targeted treatments result from the suppression of neuronal oxidative stress and inflammation in experimental diabetic rats. Naunyn Schmiedebergs Arch Pharmacol. 2020 Jul;393(7):1293-1302. doi: 10.1007/s00210-020-01871-9. Epub 2020 May 2.
PubMed 32361779Wang G, Li Z, Li S, Ren J, Suresh V, Xu D, Zang W, Liu X, Li W, Wang H, Guo F. Minocycline Preserves the Integrity and Permeability of BBB by Altering the Activity of DKK1-Wnt Signaling in ICH Model. Neuroscience. 2019 Sep 1;415:135-146. doi: 10.1016/j.neuroscience.2019.06.038. Epub 2019 Jul 22.
PubMed 31344398Pang T, Wang J, Benicky J, Saavedra JM. Minocycline ameliorates LPS-induced inflammation in human monocytes by novel mechanisms including LOX-1, Nur77 and LITAF inhibition. Biochim Biophys Acta. 2012 Apr;1820(4):503-10. doi: 10.1016/j.bbagen.2012.01.011. Epub 2012 Jan 27.
PubMed 22306153Li J, Mi X, Yang Z, Feng Z, Han Y, Wang T, Lv H, Liu Y, Wu K, Liu J. Minocycline ameliorates cognitive impairment in rats with trigeminal neuralgia by regulating microglial polarization. Int Immunopharmacol. 2025 Jan 3;145:113786. doi: 10.1016/j.intimp.2024.113786. Epub 2024 Dec 12.
PubMed 39672028Labro MT. Immunomodulatory effects of antimicrobial agents. Part I: antibacterial and antiviral agents. Expert Rev Anti Infect Ther. 2012 Mar;10(3):319-40. doi: 10.1586/eri.12.11.
PubMed 22397566Zhou Y, Xie Y, Xu M. Potential mechanisms of Treponema pallidum breaching the blood-brain barrier. Biomed Pharmacother. 2024 Nov;180:117478. doi: 10.1016/j.biopha.2024.117478. Epub 2024 Sep 24.
PubMed 39321510Zheng XQ, Li Z, Meng QQ, Li W, Li QL, Xie L, Xiao Y, Xu QY, Chen YY. Treponema pallidum recombinant protein Tp47 activates NOD-like receptor family protein 3 inflammasomes in macrophages via glycolysis. Int Immunopharmacol. 2024 Jan 5;126:111204. doi: 10.1016/j.intimp.2023.111204. Epub 2023 Nov 27.
PubMed 38016343Wang C, Zhu L, Gao Z, Guan Z, Lu H, Shi M, Gao Y, Xu H, Yang XF, Zhou P. Increased interleukin-17 in peripheral blood and cerebrospinal fluid of neurosyphilis patients. PLoS Negl Trop Dis. 2014 Jul 31;8(7):e3004. doi: 10.1371/journal.pntd.0003004. eCollection 2014.
PubMed 25080350Zhang Q, Ma J, Zhou J, Zhang H, Li M, Gong H, Wang Y, Zheng H, Li J, Leng L. A Study on the Inflammatory Response of the Brain in Neurosyphilis. Adv Sci (Weinh). 2025 Feb;12(5):e2406971. doi: 10.1002/advs.202406971. Epub 2024 Nov 22.
PubMed 39574316
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Minocycline Add-on in Patients With Neurosyphilis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial （MIN-ADD）
- ClinicalTrials.gov ID
- NCT07904533
- Acronym / sponsor ID
- MIN-ADD / DTEC-KY2026-117-03
- Conditions
- Neurosyphilis
- Keywords
- Minocycline, Penicillin G, Randomized Controlled Trial, Neurological Outcomes, Treatment, Adjunctive Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 778 participants (estimated)
- Lead sponsor
- Beijing Ditan HospitalUniversity, hospital or other
- Study start
- 15 Nov 2026 (estimated)
- Primary completion
- 22 May 2028 (estimated)
- Study completion
- 22 Dec 2028 (estimated)
- First posted
- 29 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are randomly assigned in a 1:1 ratio to either the experimental group (intravenous penicillin plus oral minocycline) or the control group (intravenous penicillin plus oral placebo). Both groups receive standard intravenous penicillin therapy for 10-14 days, followed by their respective oral study medication (minocycline or placebo) for 28 days.
| Arm | Type | Receives |
|---|---|---|
| Penicillin plus Minocycline | Experimental | Drug: Minocycline, Drug: Aqueous crystalline penicillin GParticipants will receive standard intravenous aqueous crystalline penicillin G (18-24 million units/day for 10-14 days) plus oral minocycline (200 mg loading dose on Day 1, followed by 100 mg every 12 hours) for 28 days. |
| Penicillin plus Placebo | Placebo comparator | Drug: Minocycline placebo, Drug: Aqueous crystalline penicillin GParticipants will receive standard intravenous aqueous crystalline penicillin G (18-24 million units/day for 10-14 days) plus oral matching minocycline placebo (200 mg loading dose on Day 1, followed by 100 mg every 12 hours) for 28 days. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18-80 years;
- Diagnosis of neurosyphilis according to the Guidelines for the Diagnosis and Treatment of Syphilis, Gonorrhea and Genital Chlamydia trachomatis Infection (2020);
- Cognitive impairment (MMSE 10-26) or ischemic stroke-like episodes (time from onset to randomization ≤14 days, NIHSS 1-20);
- Written informed consent provided by the patient or their legally authorized representative.
Key exclusion criteria (16 listed)
- Allergy or resistance to penicillin or tetracycline antibiotics (including minocycline).
- Intravenous or intramuscular ceftriaxone for neurosyphilis within 1 month before enrolment (a single intramuscular dose of ceftriaxone for another infection is not exclusionary).
- Use of tetracycline antibiotics within 1 month before enrolment.
- 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 <4 weeks or <5 half-lives (whichever is longer).
- Pre-morbid modified Rankin Scale (mRS) score >2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineAdministered orally. Loading dose of 200 mg on Day 1, followed by 100 mg every 12 hours for 28 days. Given only to participants in the Experimental Group. | Drug | Penicillin plus Minocycline |
| Minocycline placeboOral matching placebo to minocycline. Loading dose of 200 mg on Day 1, followed by 100 mg every 12 hours for 28 days. Given only to participants in the Control Group. | Drug | Penicillin plus Placebo |
| Aqueous crystalline penicillin GAdministered intravenously at 18-24 million units per day for 10-14 days. Given to all participants in both arms. | Drug | Penicillin plus Minocycline, Penicillin plus Placebo |
Primary outcome
Proportion of participants with favorable neurological outcomes at 6 months
Time frame: At 6 months post-treatment
Unit of measure: Percentage (%). A favorable neurological outcome is defined as meeting both of the following criteria: (1) a modified Rankin Scale score of 0 to 2, AND (2) at least one of the following: an improvement in the Mini-Mental State Examination score of ≥2 points from baseline, or a Mini-Mental State Examination score of >26. The Mini-Mental State Examination score ranges from 0 to 30, with higher scores indicating better cognitive function. The modified Rankin Scale score ranges from 0 to 6, with higher scores indicating worse disability.
18 secondary outcomes
Proportion of participants with normal cerebrospinal fluid (CSF) white blood cell counts
Time frame: At 6 months post-treatment
Proportion of participants with normal cerebrospinal fluid (CSF) protein levels
Time frame: At 6 months post-treatment
Proportion of participants with a ≥4-fold decline or seroreversion in cerebrospinal fluid (CSF) non-treponemal antibody titers
Time frame: At 6 months post-treatment
Proportion of participants with a ≥4-fold decline or seroreversion in serum non-treponemal antibody titers
Time frame: At 6 months post-treatment
Proportion of participants with a modified Rankin Scale (mRS) score of 0 to 2
Time frame: At 6 months post-treatment
Proportion of participants with a ≥2-point improvement or a score >26 in the Mini-Mental State Examination
Time frame: At 6 months post-treatment
Change from baseline in the modified Rankin Scale (mRS) score at 6 months
Time frame: At 6 months post-treatment
Change from baseline in the Mini-Mental State Examination (MMSE) score at 6 months
Time frame: At 6 months post-treatment
Change from baseline in the Montreal Cognitive Assessment (MoCA) Beijing version score at 6 months
Time frame: At 6 months post-treatment
Change from baseline in the National Institutes of Health Stroke Scale (NIHSS) score at 6 months
Time frame: At 6 months post-treatment
Change from baseline in the Lawton Activities of Daily Living Scale (Chinese 14-item revised version) score at 6 months
Time frame: At 6 months post-treatment
Change from baseline in the Beck Depression Inventory-II (BDI-II) score at 6 months
Time frame: At 6 months post-treatment
Change from baseline in the Neuropsychiatric Inventory (NPI) score at 6 months
Time frame: At 6 months post-treatment
Change from baseline in the Global Cortical Atrophy (GCA) total score at 6 months
Time frame: At 6 months post-treatment
Change from baseline in total brain lesion volume on Magnetic Resonance Imaging (MRI) at 6 months
Time frame: At 6 months post-treatment
All-cause mortality at 6 months
Time frame: Up to 6 months post-treatment
Number of participants with adverse events (AEs) at 6 months
Time frame: Up to 6 months post-treatment
Number of participants with serious adverse events (SAEs) at 6 months
Time frame: Up to 6 months post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
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- Background: PubMed 26042389Bollenbach T. Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution. Curr Opin Microbiol. 2015 Oct;27:1-9. doi: 10.1016/j.mib.2015.05.008. Epub 2015 Jun 1.
- Background: PubMed 39471409Ishak A, Mazonakis N, Spernovasilis N, Akinosoglou K, Tsioutis C. Bactericidal versus bacteriostatic antibacterials: clinical significance, differences and synergistic potential in clinical practice. J Antimicrob Chemother. 2025 Jan 3;80(1):1-17. doi: 10.1093/jac/dkae380.
- Background: PubMed 28033297Shao LL, Guo R, Shi WJ, Liu YJ, Feng B, Han L, Liu QZ. Could lengthening minocycline therapy better treat early syphilis? Medicine (Baltimore). 2016 Dec;95(52):e5773. doi: 10.1097/MD.0000000000005773.
- Background: PubMed 41628627Lu Y, Guan L, Wu J, Yang Q, Zhang M, Zhou D, Yang H, Pan Y, Wang L, Qiu B, Liu C, Wang Y, Yang Y, Zhou X, Qu H, Liao X, Liu L, Zhao X, Bath PM, Johnston SC, Amarenco P, Turc G, Shi FD, Wang Y, Wang Y; EMPHASIS Investigators. Efficacy and safety of minocycline in patients with acute ischaemic stroke (EMPHASIS): a multicentre, double-blind, randomised controlled trial. Lancet. 2026 Feb 14;407(10529):679-688. doi: 10.1016/S0140-6736(25)01862-8. Epub 2026 Jan 30.
- Background: PubMed 24971013Zhang L, Zhao J. Profile of minocycline and its potential in the treatment of schizophrenia. Neuropsychiatr Dis Treat. 2014 Jun 17;10:1103-11. doi: 10.2147/NDT.S64236. eCollection 2014.
- Background: PubMed 32361779Mert T, Sahin E, Yaman S, Sahin M. Effects of immune cell-targeted treatments result from the suppression of neuronal oxidative stress and inflammation in experimental diabetic rats. Naunyn Schmiedebergs Arch Pharmacol. 2020 Jul;393(7):1293-1302. doi: 10.1007/s00210-020-01871-9. Epub 2020 May 2.
- Background: PubMed 31344398Wang G, Li Z, Li S, Ren J, Suresh V, Xu D, Zang W, Liu X, Li W, Wang H, Guo F. Minocycline Preserves the Integrity and Permeability of BBB by Altering the Activity of DKK1-Wnt Signaling in ICH Model. Neuroscience. 2019 Sep 1;415:135-146. doi: 10.1016/j.neuroscience.2019.06.038. Epub 2019 Jul 22.
- Background: PubMed 22306153Pang T, Wang J, Benicky J, Saavedra JM. Minocycline ameliorates LPS-induced inflammation in human monocytes by novel mechanisms including LOX-1, Nur77 and LITAF inhibition. Biochim Biophys Acta. 2012 Apr;1820(4):503-10. doi: 10.1016/j.bbagen.2012.01.011. Epub 2012 Jan 27.
- Background: PubMed 39672028Li J, Mi X, Yang Z, Feng Z, Han Y, Wang T, Lv H, Liu Y, Wu K, Liu J. Minocycline ameliorates cognitive impairment in rats with trigeminal neuralgia by regulating microglial polarization. Int Immunopharmacol. 2025 Jan 3;145:113786. doi: 10.1016/j.intimp.2024.113786. Epub 2024 Dec 12.
- Background: PubMed 22397566Labro MT. Immunomodulatory effects of antimicrobial agents. Part I: antibacterial and antiviral agents. Expert Rev Anti Infect Ther. 2012 Mar;10(3):319-40. doi: 10.1586/eri.12.11.
- Background: PubMed 39321510Zhou Y, Xie Y, Xu M. Potential mechanisms of Treponema pallidum breaching the blood-brain barrier. Biomed Pharmacother. 2024 Nov;180:117478. doi: 10.1016/j.biopha.2024.117478. Epub 2024 Sep 24.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared. The data collected in this study will be used solely by the study investigators for the purposes outlined in this protocol.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xia Meng, MD principal investigator
Beijing Ditan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Minocycline and Aqueous crystalline penicillin G in people with Neurosyphilis, run by Beijing Ditan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xia Meng, MD (+86-13811821377, mengxia45@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with favorable neurological outcomes at 6 months (time frame: At 6 months post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07904533, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.