Ceftriaxone Pulse Dose for Post-Treatment Lyme Disease

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

The goal of this clinical trial is to learn if an FDA approved drug, Ceftriaxone, given intermittently, can treat people between 18 and 75 years old with a history of Lyme disease, who are still experiencing persistent or returning symptoms after they have completed treatment. The main questions it aims to answer are:

• Will giving Ceftriaxone approximately every 5 days for 6 weeks be safe and well tolerated when compared to a group that receives placebo (a look-alike substance that contains no drug)?
• Will giving Ceftriaxone improve symptoms?

Participants will be asked to do the following:

• Come to the clinic approximately every 5-6 days to receive an IV infusion of either the Ceftriaxone or placebo.
• Answer questions about their level of tiredness, body pain, general health and physical ability, sleep, anxiety, depression and any suicidal thoughts.
• Give blood so we can make sure your body is handling the drug okay or to help us learn more about how the drug is affecting the persistent Lyme disease symptoms.

Study Overview

• Status: Recruiting
• Conditions: Post-Treatment Lyme Disease
• Intervention / Treatment: Drug: Ceftriaxone (Rocephin®); Drug: Dextrose 5% (D5W)

Detailed Description

This study will explore treating participants who are 18 to 75 years old with Post-Treatment Lyme Disease. IV Ceftriaxone will be delivered in a pulse dose fashion, approximately every 5 days for a total of 9 IV infusions over 6 weeks. Participants will return one month following last treatment, at approximately 3 and 6 months from study start. At each study visit, participants will be asked a number of questionnaires including the SAFTEE assessment to assess the side effects of the drug as compared to placebo; the Fatigue Severity Scale, SF-36, GSQ-30, and PROMIS-29 questionnaires to assess physical functioning, general health, vitality, social functioning, bodily pain, role physical, role emotional, mental health, symptoms, fatigue, anxiety, depression, and sleep disturbances; the CSSRS to assess suicidal ideation.

At the 6-month mark, the study will be unblinded and participants in the placebo group will be invited to repeat the study visits receiving Ceftriaxone. Participants who originally received Ceftriaxone will receive a phone call follow up at 1 year. The duration for both groups is one year. Samples will be collected for safety labs and research assessments.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Keely Terrillion; Phone Number: 315-464-9869; Email: trials@upstate.edu

Study Locations

• United States
  • New York
    • East Syracuse, New York, United States, 13057
      • Recruiting
      • SUNY Upstate Medical University, Upstate Global Health Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 to 75 at the time of consent
2. Ability and willingness to sign informed consent
3. Available for the study period
4. Must have met the definition of a prior well-defined or probable Lyme disease infection, AND meet the definition of PTLDS
5. Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit
6. 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)
7. 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:

1. Female: pregnant or lactating
2. Women who intend to become pregnant during the treatment study period (approximately 45 days)
3. Patients with a diagnosis of Lyme disease based on only a positive Lyme IgM immunoblot
4. A history of cephalosporin allergy or significant intolerance
5. Lyme related symptoms that have been present for greater than 10 years

6. 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 greater than 200 will be allowed to participate.

7. 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 as identified by a rating of moderate or high risk on the CSSRS assessment), which in the opinion of the investigator prevents the subject from participating in the study
8. 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 erythematous, Sjogren's syndrome, scleroderma, psoriasis, fibromyalgia, chronic fatigue syndrome/myalgic encephalomyelitis, or obstructive sleep apnea
9. 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)
10. 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)
11. Significant screening physical examination abnormalities or chronic medical condition that in the opinion of the investigator may impact subject safety
12. 12. Participation (active or follow-up phase) or planned participation in another vaccine, drug, or medical device in the 4 weeks prior to this trial, within 5 times the elimination half-life, whichever is longer, or during the trial
13. Prior history of Clostridium difficile infection
14. Currently taking warfarin (Coumadin)
15. Unable to comply with study requirements
16. Clinician discretion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ceftriaxone; Participants will receive IV infusion of 2g Ceftriaxone, approximately every 5 days for 6 weeks for a total of 9 treatments.	Drug: Ceftriaxone (Rocephin®); Slightly yellow liquid.
Placebo Comparator: Placebo; Participants will receive IV infusion of dextrose 5% in water, approximately every 5 days for 6 weeks for a total of 9 treatments	Drug: Dextrose 5% (D5W); Colorless liquid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of abnormal laboratory measurements	Total number of all abnormal labs	30 days post last treatment
Intensity of Abnormal Laboratory Measurements	Graded according clinical laboratory normals and FDA toxicity scale	30 days post final treatment
Duration of Abnormal Laboratory Measurements	Number of days of abnormal lab	30 days post final treatment
Occurrence of adverse events	Total number of adverse events	30 days post last treatment
Intensity adverse events	Graded according FDA toxicity scale	30 days post final treatment
Duration of adverse events	Number of days per adverse event	30 days post final treatment
Number of serious adverse events	Total number	1 year post study start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue Severity Scale	Clinical improvement	At 6 and 12 months
SF-36 continuous variables	Primary functional change with physical and mental summary indices as continuous variables.	6 and 12 months
SF-36 Responder-Nonresponder	Primary functional change with the physical and mental summary indices as either responder or nonresponder.	6 and 12 months
General Symptom Questionnaire	Changes in secondary clinical outcomes	6 and 12 months
PROMIS-29	Changes in secondary clinical outcomes	6 and 12 months
Lyme VlsE1/pepC10 Antibody	Changes in quantitative antibody levels	6 and 12 months
SAFTEE assessment	Adverse events	1 month post last dose

Collaborators and Investigators

• Sponsor: State University of New York - Upstate Medical University
• Collaborators: Steven & Alexandra Cohen Foundation
• Investigators: Principal Investigator: Kristopher Paolino, MD, State University of New York - Upstate Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 23, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 24, 2024

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Ceftriaxone; Chronic Lyme Disease; Pulse Dose; 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; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbohydrates; Amides; Sugars; beta-Lactams; Lactams; Cephalosporins; Thiazines; Hexoses; Monosaccharides; Cefotaxime; Cephacetrile; Ceftriaxone; Glucose
• Other Study ID Numbers: 2024-02-UMU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlies the primary results in a publication.
• IPD Sharing Time Frame: IPD will be shared with the primary publication.
• IPD Sharing Access Criteria: Primary IPD will be published with the primary manuscript describing the study. Requests for additional information can be requested by emailing warel@upstate.edu.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No