Ceftriaxone for Chronic Lyme Disease

Overseen By Keely Terrillion

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: State University of New York - Upstate Medical University

Must not be taking: Warfarin

Disqualifiers: Pregnancy, Cephalosporin allergy, HIV, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 6 weeks

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether the antibiotic Ceftriaxone can aid individuals with ongoing Lyme disease symptoms after completing initial treatment. Participants will receive either Ceftriaxone or a placebo via IV every 5 days for 6 weeks to assess the treatment's safety and its effect on symptoms like fatigue and body pain. This trial may suit those previously diagnosed with Lyme disease who continue to experience fatigue that disrupts daily activities and have been off antibiotics for at least 6 weeks. As an Early Phase 1 trial, the research focuses on understanding how Ceftriaxone affects people with persistent Lyme disease symptoms.

Will I have to stop taking my current medications?

The trial requires that participants stop taking antibiotics used to treat Lyme disease, such as doxycycline, amoxicillin, cefuroxime, azithromycin, ceftriaxone, or penicillin, for at least 6 weeks before joining and remain off them during the study. If you are taking other medications, the protocol does not specify, so it's best to discuss with the study team.

Is there any evidence suggesting that Ceftriaxone is likely to be safe for humans?

Research has shown that Ceftriaxone is generally safe for treating Lyme disease symptoms. Studies have found that patients usually tolerate it well. One study found Ceftriaxone more effective than a placebo in improving symptoms for those with post-treatment Lyme disease, with no reports of severe side effects.

The FDA has already approved Ceftriaxone for other uses, indicating a well-understood safety profile. While some side effects can occur, they are usually mild and manageable, such as reactions at the injection site or digestive issues.

Overall, Ceftriaxone has a history of safety when used correctly, but ongoing studies will help confirm these findings for people with persistent Lyme disease symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ceftriaxone is unique in the treatment of chronic Lyme disease because it is administered intravenously, allowing it to directly enter the bloodstream and potentially reach higher concentrations at the site of infection. Unlike standard oral antibiotics, which are the usual approach, this method could improve its effectiveness against persistent Lyme bacteria. Researchers are excited about ceftriaxone's potential to target the disease more aggressively and offer relief to patients who haven't responded to traditional treatments.

What evidence suggests that Ceftriaxone might be an effective treatment for chronic Lyme disease?

Research has shown that Ceftriaxone, which participants in this trial may receive, can help treat Lyme disease symptoms. One study found that 90% of patients with nerve-related symptoms improved after using Ceftriaxone. Another study showed that most patients felt better after a 14-day treatment with Ceftriaxone. Additionally, research comparing treatments found that Ceftriaxone was more effective than a placebo and another antibiotic, doxycycline, for ongoing Lyme disease symptoms. These findings suggest Ceftriaxone could benefit those still experiencing symptoms after standard treatment. ^{2 3 6 7 8}

Who Is on the Research Team?

Kristopher Paolino, MD

Principal Investigator

State University of New York - Upstate Medical University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 who have had Lyme disease and are still feeling sick after treatment. They must be able to come to the clinic every 5-6 days for an IV infusion and answer health questions.

Inclusion Criteria

Ability and willingness to sign informed consent

Available for the study period

I experience fatigue that affects my daily activities.

Exclusion Criteria

Clinician discretion

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)

Patients with a diagnosis of Lyme disease based on only a positive Lyme IgM immunoblot

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IV infusion of Ceftriaxone or placebo approximately every 5 days for 6 weeks, totaling 9 treatments

6 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits at 1 month, 3 months, and 6 months from study start

6 months

3 visits (in-person)

Open-label extension

Study unblinded at 6 months; placebo group invited to repeat study with Ceftriaxone, original Ceftriaxone group receives phone follow-up at 1 year

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ceftriaxone

Trial Overview The study tests if Ceftriaxone, given every five days over six weeks, is safe and can improve symptoms of persistent Lyme disease compared to a placebo (a substance with no drug).

How Is the Trial Designed?

Group I: Ceftriaxone Active Control 1 Intervention

Participants will receive IV infusion of 2g Ceftriaxone, approximately every 5 days for 6 weeks for a total of 9 treatments.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive IV infusion of dextrose 5% in water, approximately every 5 days for 6 weeks for a total of 9 treatments

Ceftriaxone is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Rocephin for:

• Sepsis
• Bacterial infections
• Meningitis
• Gonorrhea
• Pelvic inflammatory disease

Approved in United States as Rocephin for:

• Sepsis
• Bacterial infections
• Meningitis
• Gonorrhea
• Pelvic inflammatory disease
• Lower respiratory tract infections
• Skin and skin structure infections
• Urinary tract infections

Approved in Canada as Rocephin for:

• Sepsis
• Bacterial infections
• Meningitis
• Gonorrhea
• Pelvic inflammatory disease
• Lower respiratory tract infections
• Skin and skin structure infections
• Urinary tract infections

Who Is Running the Clinical Trial?

State University of New York - Upstate Medical University

Lead Sponsor

Trials

176

Recruited

27,600+

Steven & Alexandra Cohen Foundation

Collaborator

Trials

10

Recruited

320+

Published Research Related to This Trial

From 1993 to 2010, the primary medications for managing lupus erythematosus (LE) remained largely unchanged, with prednisone and hydroxychloroquine being the most frequently prescribed treatments by various specialists.

The study revealed a shift in prescribing patterns, where hydroxychloroquine became the leading medication from 2005 to 2010, while prednisone dropped to the second position, indicating a potential change in treatment preferences among physicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in the outpatient medication management of lupus erythematosus in the United States. Sugai, DY., Gustafson, CJ., De Luca, JF., et al.[2015]

In a double-blind study of 60 patients with inflammatory arthritis, 19 out of 40 patients treated with ceftriaxone showed improvement, suggesting that some cases of chronic inflammatory arthritis may respond to antibiotic therapy, potentially indicating a bacterial origin.

Despite the initial positive response, 16 of the 27 patients who improved experienced a worsening of their arthritis 6 to 18 months later, highlighting the need for further research into the long-term effects and underlying causes of chronic inflammatory arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftriaxone therapy of chronic inflammatory arthritis. A double-blind placebo controlled trial. Caperton, EM., Heim-Duthoy, KL., Matzke, GR., et al.[2022]

In a study of 23 patients with late Lyme disease, ceftriaxone was significantly more effective than penicillin, with only 1 out of 13 patients experiencing treatment failure compared to 5 out of 10 with penicillin.

Further treatment with ceftriaxone at doses of 4 g/day or 2 g/day showed similar success rates, suggesting that ceftriaxone is a reliable option for treating late Lyme disease, especially in patients who have not previously received corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of late Lyme borreliosis--randomised comparison of ceftriaxone and penicillin. Dattwyler, RJ., Halperin, JJ., Volkman, DJ., et al.[2019]

In a study of 35 patients with late-stage Lyme borreliosis treated with a 14-day course of ceftriaxone, 73% showed complete response or marked improvement after 36 months, indicating the treatment's efficacy.

Ceftriaxone was well tolerated, with no patients needing to discontinue treatment due to adverse reactions, highlighting its safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results in patients with Lyme arthritis following treatment with ceftriaxone. Valesová, H., Mailer, J., Havlík, J., et al.[2019]

A case study highlights the risks of empiric antibiotic treatment in patients suspected of having Lyme disease, as a patient treated with intravenous ceftriaxone developed serious complications despite negative tests for the disease.

The complications included granulocytopenia, fever, hepatitis, and Clostridium difficile-associated diarrhea, emphasizing the need for physicians to carefully consider the risks of treating without definitive evidence of Lyme disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-threatening complications of empiric ceftriaxone therapy for 'seronegative Lyme disease'. Nadelman, RB., Arlin, Z., Wormser, GP.[2019]

Effective management of cutaneous lupus erythematosus (CLE) relies heavily on sun protection and the use of antimalarial agents as first-line treatments, particularly for discoid and subacute forms of the disease.

For chronic and refractory cases, systemic immunosuppressive agents and local corticosteroids are crucial, with thalidomide being a valuable option for difficult cases, although it has significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous lupus erythematosus: diagnosis and management. Fabbri, P., Cardinali, C., Giomi, B., et al.[2018]

Ceftriaxone is highly effective against Lyme disease, with a minimum bactericidal concentration (MBC) of 0.050 microg/ml for Borrelia burgdorferi, the bacteria causing the disease.

In a study with C3H mice, a 5-day regimen of ceftriaxone (50 mg/kg/dose) was 100% effective in sterilizing infected tissues, suggesting that shorter antibiotic courses could be effective for treating early uncomplicated Lyme disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of short-course ceftriaxone therapy for Borrelia burgdorferi infection in C3H mice. Pavia, C., Inchiosa, MA., Wormser, GP.[2021]

The case highlights the occurrence of erysipelas as a complication in a patient with chronic discoid lupus erythematosus (CDLE) affecting the face, emphasizing the need for careful monitoring in such patients.

The review discusses the evolving patterns and clinical features of erysipelas, suggesting that healthcare providers should be aware of these changes for better diagnosis and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erysipelas complicating chronic discoid lupus erythematosus of the face--a case report and review of erysipelas. Keefe, M., Wakeel, RA., Kerr, RE.[2019]

The patient with subacute cutaneous lupus erythematosus exhibited severe skin symptoms and low complement levels, indicating an autoimmune response, as confirmed by skin biopsy and immunofluorescence studies.

Initial treatments including prednisolone, chloroquine, cyclosporine, and gold were ineffective, but the condition was successfully managed with dapsone and a higher dose of prednisolone, highlighting the importance of treatment adjustments in autoimmune skin diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Widespread pruritic plaques in a patient with subacute cutaneous lupus erythematosus and hypocomplementemia: response to dapsone therapy. Tsutsui, K., Imai, T., Hatta, N., et al.[2019]

In a clinical trial involving 46 patients with neuroborreliosis, a 14-day treatment with 2 g of ceftriaxone once daily resulted in a 30% cure rate at the end of treatment and an 85% cure rate after 9 months for those with early Lyme neuroborreliosis.

The treatment was generally safe, with no patients needing to stop due to adverse reactions, although one patient died from a cardiac infarction unrelated to the antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftriaxone in the treatment of Lyme neuroborreliosis. Rohácová, H., Hancil, J., Hulinská, D., et al.[2022]

A 61-year-old woman with systemic lupus erythematosus developed facial erysipelas, which was initially misdiagnosed as a lupus flare, highlighting the importance of accurate diagnosis in patients with complex medical histories.

The patient improved significantly with intravenous antibiotics and a rapid tapering of corticosteroids, demonstrating that appropriate treatment is crucial for conditions that may mimic lupus flares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A red face in a lupus patient: thinking beyond lupus rash. Stubbe, M., Smith, V., Thevissen, K., et al.[2016]

A 58-year-old male with Lyme disease initially treated with oral doxycycline showed no improvement, indicating that some patients may not respond to standard treatment.

The patient's symptoms improved significantly after switching to intravenous ceftriaxone, suggesting that alternative treatments may be necessary for refractory cases of Lyme disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Chronic Symptoms of Lyme Disease With Intravenous Ceftriaxone. Naeem, M., Enos, D., Shah, S., et al.[2021]

Doxycycline is as effective as ceftriaxone for treating chronic Lyme borreliosis with central nervous system symptoms, based on a study of 46 patients over a 12-month follow-up period.

Doxycycline is significantly cheaper than ceftriaxone, although it may cause more gastrointestinal symptoms and photosensitivity reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxycycline versus ceftriaxone for the treatment of patients with chronic Lyme borreliosis. Ogrinc, K., Logar, M., Lotric-Furlan, S., et al.[2018]

Citations

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A comparison of two treatment regimens of ceftriaxone in ... Conclusions: Ceftriaxone for 14 days eradicated the signs and symptoms of late Lyme disease in the majority of evaluable patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06611111

Ceftriaxone Pulse Dose 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 ...

3. nejm.org nejm.org/doi/full/10.1056/NEJM199707313370501

Ceftriaxone Compared with Doxycycline for the Treatment ... Pfister et al. reported that 90 percent of patients with neurologic sequelae of Lyme disease had a favorable outcome after treatment with ...

4. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-07989-4

Efficacy and safety of antibiotic therapy for post-Lyme disease ... The network meta-analysis showed that ceftriaxone had better results than placebo [Mean = 0.87, 95% CI (0.02, 1.71)] and doxycycline [Mean = ...

5. openneurologyjournal.com openneurologyjournal.com/VOLUME/6/PAGE/79/FULLTEXT/

A Reappraisal of the U.S. Clinical Trials of Post-Treatment ... Results: 2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures. Conclusions: Future ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8852482/

Long-term Results in Patients With Lyme Arthritis Following ... The treatment results in this group of 35 patients with Lyme arthritis are considered successful. The data obtained are consistent with expectations based on ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1505425

Randomized Trial: Longer Therapy for Lyme Symptoms We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term ...

8. idsociety.org idsociety.org/practice-guideline/lyme-disease/

Lyme Disease Treatment of Lyme disease-associated meningitis is effective using IV cefotaxime or ceftriaxone, meningeal dose IV penicillin, or oral ...