Pulse-dosed intravenous ceftriaxone for persistent post‑Lyme symptoms

Phase 1/2, Randomized, Double-Blind, Placebo-Controlled Trial of Pulse Dosed Ceftriaxone for Post-Treatment Lyme Disease

This trial will try pulse-dosed IV ceftriaxone every 5 days for about 6 weeks to see if it kills lingering Lyme infection in adults with Post‑Treatment Lyme Disease Syndrome.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Hackensack Meridian Health (Academic / other)
• Locations: 1 site (Hackensack, New Jersey)
• Trial ID: NCT06785402 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 randomized, placebo‑controlled study assigns adults with PTLDS 1:1 to receive either pulse‑dosed IV ceftriaxone or placebo (D5W) roughly every 5 days for about six weeks. Participants are evaluated at each study visit, unblinded at six months, and those who received placebo are offered the active regimen after unblinding. Safety and symptom outcomes are followed out to 12 months from treatment start. The study requires participants to have had a prior well‑defined or probable Lyme infection, meet PTLDS criteria, and be off antibiotics targeting Lyme for at least six weeks before enrollment.

Who should consider this trial

Good fit: Adults 18–75 with a prior well‑defined or probable Lyme infection who meet the PTLDS definition, report significant fatigue (FSS ≥4), are off Lyme‑directed antibiotics for at least six weeks, and can attend IV infusion visits are ideal candidates.

Not a fit: People who are pregnant, unable or unwilling to stop antibiotics, outside the 18–75 age range, or whose symptoms are not due to persistent infection (for example primarily autoimmune or noninfectious causes) may not benefit.

Why it matters

Potential benefit: If successful, the approach could reduce fatigue and other persistent symptoms by eradicating a lingering Lyme infection in some patients.

How similar studies have performed: Previous randomized studies of prolonged antibiotics for PTLDS have shown mixed and mostly transient benefits, so pulse‑dosed ceftriaxone is a relatively novel approach without established, durable proof of benefit.

Eligibility criteria

Inclusion Criteria:

* Age 18 to 75 years at the time of consent
* Ability and willingness to sign informed consent
* Available for the study period
* Must have met the definition of a prior well-defined or probable Lyme disease infection, AND meet the definition of PTLDS
* Provide consent for release of medical history records and photographs from primary care physician, college or university, urgent care or emergency room visit
* Have a level of fatigue that interferes with their ability to function in their job, schooling, or other social/personal activities (FSS score of 4 or higher)
* Subjects will need to have been off of antibiotics (those standard antibiotics used to target Lyme disease to include doxycycline, amoxicillin, cefuroxime, azithromycin, ceftriaxone or penicillin) for at least 6 weeks prior to study enrollment and be willing to remain off of any outside antibiotics during the duration of the treatment component of the study.

Exclusion Criteria:

* Female: pregnant or lactating
* Women who intend to become pregnant during the treatment study period (approximately 45 days)
* Patients with a diagnosis of Lyme disease based on only a positive Lyme IgM immunoblot
* A history of cephalosporin allergy or significant intolerance
* Lyme related symptoms that have been present for greater than 10 years
* Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus.

Note: Subjects who have well controlled HIV, who are on ART with a CD4 count of \>200 will be allowed to participate.

* Diagnosis with Bipolar Disorder or Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition to include any finding of increased suicide risk per the CSSRS scale (score 6 or greater), which in the opinion of the investigator prevents the subject from participating in the study
* Known concurrent rheumatologic or similar disease thought to interfere with study participation or confound results at the discretion of the investigator. These may include but are not limited to rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, scleroderma, psoriasis, fibromyalgia, chronic fatigue syndrome/myalgic encephalomyelitis, or obstructive sleep apnea
* Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous treatment with a cephalosporin antibiotic, or severe allergic reaction to penicillins (e.g. anaphylaxis or severe rash with Stevens Johnson syndrome or similar)
* Planned travel during the study period that would interfere with the ability to complete all study visits (this can be a temporary exclusion with plan to schedule enrollment during a window of time during which they could attend their study visits)
* Significant screening physical examination abnormalities or chronic medical condition that in the opinion of the investigator may impact subject safety
* Participation (active or follow-up phase) or planned participation in another vaccine, drug, or medical device in the 4 weeks prior to this trial or during the trial
* Prior history of Clostridium difficile infection
* Unable to comply with study requirements
* Clinician discretion

Where this trial is running

Hackensack, New Jersey

• Hackensack University Medical Center — Hackensack, New Jersey, United States (Recruiting)

Study contacts

• Principal investigator: Bindu Balani, MD — Hackensack Meridian Health
• Study coordinator: Bindu Balani, MD

Conditions Post-Treatment Lyme Disease Syndrome; Post-Treatment Lyme disease Syndrome; Ceftriaxone; Persistent Symptoms