Ceftriaxone for Post-Treatment Lyme Disease

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

Lyme disease is a public health crisis in the US. It is estimated that over 400,000 cases occur every year with 10-20% of those infected going on to develop Post-Treatment Lyme disease Syndrome (PTLDS). The goal of this study is to investigate if giving Ceftriaxone every 5 days for about 6 weeks kills the organism that produces persistent Lyme infection.

Enrolled participants will be randomized 1:1 receiving either pulse-dosed ceftriaxone or placebo [dextrose (5% in water), (D5W)], intravenously. Participants will be evaluated at each of the study visits, and then in a follow-up phase out to 12 months. They will be unblinded at 6 months and those randomized to the placebo group will be offered pulse-dosed ceftriaxone on the same schedule as those randomized to the drug group. All patients will be followed up for a total of 12 months post treatment initiation.

Study Overview

• Status: Withdrawn
• Conditions: Post-Treatment Lyme Disease Syndrome
• Intervention / Treatment: Drug: Ceftriaxone treatment; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftriaxone 2 GM; Administration of IV ceftriaxone or D5W. Subjects will be infused approximately every 5 days (+/- 1 day) over the course of ~6 weeks. Subjects will receive a total of 9 infusions throughout the treatment phase of the study, with the last infusion tentatively scheduled for Day 41 (+/- 3 days).	Drug: Ceftriaxone treatment; 9 infusions spaced out approximately every 5 days
Placebo Comparator: Placebo; Placebo [dextrose (5% in water), (D5W)] IV following the same infusion schedule as the ceftriaxone arm.	Drug: Placebo; D5W (placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of pulse-dosed ceftriaxone	To assess the safety of pulse-dosed ceftriaxone in PTLDS when compared to placebo as well as historical data based on the number of reported adverse and serious adverse events.	12 months post treatment initiation
Tolerability of pulse-dosed ceftriaxone	To assess the tolerability of pulse-dosed ceftriaxone in PTLDS when compared to placebo as well as historical data based on the number of reported adverse and serious adverse events.	12 months post treatment initiation
Study Feasibility	To assess the recruit the patients within the pre-determined period of time (6 months).	6 month enrollment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement - Physical and mental summary indices	To assess clinical improvement after treatment using additional clinical outcome measures. Primary functional change with the physical and mental summary indices of the SF-36 as either responder or non-responder (a change of 6.5 points on the SF-physical health summary scale, and 7.9 points on the mental health summary scale respectively). Eight scales are used and when combined measure the physical and mental health of participants. Each scale is scored to have same average (50) and the same standard deviation (10 points). with a score below 50 representing below average health.	12 months post treatment initiation
Clinical Improvement - General Symptom Questionnaire (GSQ-30)	To assess clinical improvement after treatment using additional clinical outcome measures. General Symptom Questionnaire (GSQ-30).GSQ-30 us used to assess symptom burden and specifically pain/fatigue, neuropsychiatric, neurologic, and viral-like symptom burden impacting function. Each symptom is measured on scale of 0 (not at all) to 4 (very much) for an overall score of 0-120 with higher scores representing higher burden.	12 months post treatment initiation
Clinical Improvement - PROMIS-29	To assess clinical improvement after treatment using additional clinical outcome measures using PROMIS-29 which has multiple sections and scoring varies by section. The min/max are as follows: Physical Function (PF) 4-20, Anxiety 4-20, Depression 4-20, Fatigue 4-20, Sleep Disturbance- 4-20, Ability to Participate in Social Roles and Activities (APSRA) 4-20, Pain Interference 4-20, Pain Intensity 0-10. For PF and APSRA, improvement would be tracked by an increase in score. For Anxiety, Depression, Fatigue, Sleep Disturbance, Pain interference, and Pain Intensity improvement would be tracked by a decrease in score. A higher score in PF and APSRA suggest better health. A higher score in Anxiety, Depression, Fatigue, Sleep Disturbance, Pain interference and Pain Intensity suggests lower health. A score change of 5 points or more is considered clinically meaningful.	12 months post treatment initiation
Clinical Improvement - Quantitative Lyme VlsE1/pepC10 Ab	To assess clinical improvement after treatment using additional clinical outcome measures changes in quantitative Lyme VlsE1/pepC10 Ab. Higher titers represent higher antibodies.	12 months post treatment initiation

Collaborators and Investigators

• Sponsor: Hackensack Meridian Health
• Collaborators: Columbia Clinical Trials Network for Lyme and Other Tick-Borne Diseases
• Investigators: Principal Investigator: Bindu Balani, MD, Hackensack Meridian Health

Study record dates

Study Major Dates

• Study Start (Estimated): May 14, 2026
• Primary Completion (Actual): May 14, 2026
• Study Completion (Actual): May 14, 2026

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): January 21, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ceftriaxone; Persistent Symptoms; Post-Treatment Lyme disease Syndrome (PTLDS)
• Additional Relevant MeSH Terms: Vector Borne Diseases; Post-Infectious Disorders; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Lyme Disease; Pathological Conditions, Signs and Symptoms; Post-Lyme Disease Syndrome; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: Pro2024-0373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No