Clinical trial NCT06611111: Ceftriaxone Pulse Dose for Post-Treatment Lyme Disease
Official title: Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial of Pulse Dosed Ceftriaxone for Post-Treatment Lyme Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Post-Treatment Lyme Disease
Keywords: Pulse Dose
Ceftriaxone
PTLDS
Chronic Lyme Disease
Lead sponsor: State University of New York - Upstate Medical University
Sponsor class: OTHER
Collaborators: name: Steven & Alexandra Cohen Foundation
First posted: 2024-09-24
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants who meet inclusion/exclusion criteria will be randomized 1:1 into receiving ceftriaxone or placebo. At day 181, the study will be unblinded and participants in the placebo group will be invited to receive ceftriaxone on the same schedule.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of abnormal laboratory measurements
timeFrame: 30 days post last treatment
measure: Intensity of Abnormal Laboratory Measurements
timeFrame: 30 days post final treatment
measure: Duration of Abnormal Laboratory Measurements
timeFrame: 30 days post final treatment
measure: Occurrence of adverse events
timeFrame: 30 days post last treatment
measure: Intensity adverse events
timeFrame: 30 days post final treatment
measure: Duration of adverse events
timeFrame: 30 days post final treatment
measure: Number of serious adverse events
timeFrame: 1 year post study start
Secondary outcomes:
measure: Fatigue Severity Scale
timeFrame: At 6 and 12 months
measure: SAFTEE assessment
timeFrame: 1 month post last dose
measure: SF-36 continuous variables
timeFrame: 6 and 12 months
measure: SF-36 Responder-Nonresponder
timeFrame: 6 and 12 months
measure: General Symptom Questionnaire
timeFrame: 6 and 12 months
measure: PROMIS-29
timeFrame: 6 and 12 months
measure: Lyme VlsE1/pepC10 Antibody
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: East Syracuse
country: United States
facility: SUNY Upstate Medical University, Upstate Global Health Institute
state: New York
Study officials:
affiliation: State University of New York - Upstate Medical University
name: Kristopher Paolino, MD
role: PRINCIPAL_INVESTIGATOR
References: