Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04038346
Other study ID # PRO18110151
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date October 1, 2019
Est. completion date December 31, 2028

Study information

Verified date December 2023
Source University of Pittsburgh
Contact Desiree NW Neville, MD
Phone 412-692-7692
Email desiree.neville@chp.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Lyme arthritis resolves with appropriate antimicrobial treatment in a majority of patients, but 10-20% of patients develop antibiotic-refractory Lyme arthritis with prolonged arthritis symptoms and treatment courses. Excessive up-regulation of the inflammatory process has been shown in patients with antibiotic-refractory Lyme arthritis. The over-expressed pro-inflammatory cell mediators are downstream of NSAID inhibition, which would suggest initial inflammatory inhibition may be beneficial in these patients. While NSAIDs are known to reduce pro-inflammatory cell mediators early in the course of inflammation, research has shown that there are other cytokines that play a role in the healing after inflammation that are also inhibited by NSAIDs, and that NSAID use can delay healing. It is not known if scheduled NSAID therapy will reduce, increase, or have no effect on the occurrence of refractory Lyme arthritis cases. The hypothesis of the study is that prescribing scheduled NSAIDs at the time of diagnosis of Lyme arthritis can prevent the development of the excessive inflammatory phase and decrease the number of patients with antibiotic-refractory Lyme arthritis, or at least decrease the duration of persistent Lyme arthritis symptoms. The pilot study design randomizes patients to scheduled NSAIDs, scheduled acetaminophen, or scheduled NSAIDs x 1 week than acetaminophen. Primary outcomes are duration of arthritis symptoms, number of refractory cases, side effects and compliance.


Description:

Specific Aims: 1. Demonstrate feasibility to ensure adequate patient enrollment and symptomatic follow-up of patients with Lyme arthritis. 2. Develop pilot data necessary for sample size and power calculations: The purpose of the research study is to evaluate whether there is symptomatic benefit of schedule NSAID therapy in patients with Lyme arthritis diagnosis. 1. Quantification of antibiotic-refractory Lyme arthritis in our population 2. Symptomatic outcomes of patients with Lyme arthritis on scheduled NSAIDs versus those not placed on scheduled NSAIDs (duration to resolution and number of patients with resistant arthritis) 3. Assess side effects of patients with Lyme arthritis placed on scheduled NSAIDs versus those not placed on scheduled NSAIDs 4. Assess changes in resources (follow-up visits, further prescriptions) required for patients taking scheduled NSAIDs versus not taking scheduled NSAIDs Background: Lyme disease is the systemic tick-borne disease caused by Borrelia burgdorferi infection, and is endemic to an expanding portion of the United States. Lyme arthritis is a common presentation of Lyme disease. While Lyme arthritis resolves with appropriate antimicrobial treatment in a majority of patients, 10-20% of patients develop antibiotic-refractory Lyme arthritis with prolonged inflammatory arthritis. Research suggests excessive up-regulation of the inflammatory process in patients with prolonged symptoms. The over-expressed pro- inflammatory cell mediators are downstream of NSAID inhibition, which would suggest NSAIDs may be beneficial in these patients. In fact, there is data that NSAIDs and/or disease-modifying anti-rheumatic drugs (DMARDs) may be beneficial in refractory Lyme arthritis cases, once diagnosed as refractory. The hypothesis of the study is that prescribing scheduled NSAIDs at the time of diagnosis can prevent the development of the excessive inflammatory phase and decrease the number of patients with antibiotic-refractory Lyme arthritis, or at least decrease the duration of persistent Lyme arthritis symptoms. There are no known methods to identify patients who will develop antibiotic-refractory Lyme arthritis. This work is important to delineate optimal timing and duration of NSAIDs given the research that shows the anti- inflammatory effects during healing can potentially delay recovery. Significance: While antibiotic-refractory Lyme arthritis has been studied at a microbiologic/cytokine level as well as evaluated in terms of treatment once patients have been deemed antibiotic refractory, to our knowledge there are no published studies evaluating prevention. With no literature looking at the question of NSAIDs for the prevention of antibiotic- refractory Lyme arthritis, this pilot study is needed to adequately calculate sample size and power calculations for a large-scale multicenter study. There is anecdotal data from the Rheumatology and Infectious Disease departments at the UPMC Children's Hospital of Pittsburgh that early scheduled NSAIDs may decrease refractory cases, but there has been no formal evaluation into this question. Retrospective evaluation is challenging since the medications in question (NSAIDs) are over the counter, and clinicians may recommend scheduled or intermittent NSAID therapy without documentation, and certainly without prescriptions in the medical record. Many patients with refractory Lyme arthritis are placed on NSAIDs, but given the question of delayed healing with inhibition of prostaglandins during the healing phase of inflammation, the question of whether NSAIDs are beneficial in patients to prevent refractory arthritis is worthwhile rather than the current process of variable NSAID prescription.


Recruitment information / eligibility

Status Recruiting
Enrollment 300
Est. completion date December 31, 2028
Est. primary completion date December 31, 2028
Accepts healthy volunteers No
Gender All
Age group 3 Years to 17 Years
Eligibility Inclusion Criteria: - Arthritis - Undergoing Lyme disease testing (Lyme test positive) Exclusion Criteria: - Patients will be secondarily withdrawn from analysis and instructed to stop study medication if their Lyme test is negative. Underlying diagnosis of rheumatoid or recurrent arthritis Already on scheduled NSAIDs Anything that restricts the prescription of naproxen or acetaminophen: - Hypersensitivity to naproxen (for example: anaphylactic reactions, serious skin reactions) or any component of the formulation; history of aspirin induced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs, underlying kidney or liver impairment - Already taking daily NSAIDs (naproxen or ibuprofen) or daily acetaminophen - Hypersensitivity to acetaminophen or any component of the formulation; severe liver impairment or severe active liver disease

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Naproxen
Patients will be randomized to an NSAID (naproxen)
Acetaminophen
Patients will be randomized to acetaminophen

Locations

Country Name City State
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Desiree Neville, MD

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Need for further care as determined by medical record review as number of visits in the system for Lyme arthritis symptoms Mean repeat medical visits for Lyme arthritis will be compared between treatment arms based on medical record review 30 days, 60 days, 120 days, 1 year
Primary Change in the degree of joint pain determined by serial visual analog scale for pain via text surveys 0-100 scale (no pain to worst pain - higher score, worse outcome), slide bar in text survey, VAS score rate of change will be compared between treatment arms, and time to normalization days 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected, time to symptom resolution will be recorded
Primary Change in the degree of joint redness determined by serial visual analog scale for joint redness via text surveys 0-100 scale (no redness to maximal redness- higher score, worse outcome), slide bar in text survey, VAS score rate of change will be compared between treatment arms, and time to normalization days 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected, time to symptom resolution will be recorded
Primary Change in degree of joint movement determined by serial visual analog scale for joint movement via text surveys 0-100 scale (no joint movement to normal joint movement- higher score, better outcome), slide bar in text survey, VAS score rate of change will be compared between treatment arms, and time to normalization days 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected, time to symptom resolution will be recorded
Primary Change in degree of overall function determined by serial visual analog scale for overall function via text surveys 0-100 scale (severely impaired function to normal function- higher score, better outcome), slide bar in text survey, VAS score rate of change will be compared between treatment arms, and time to normalization days 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected, time to symptom resolution will be recorded
Primary Time to complete symptom resolution as collected by a yes/no question on the text survey and a branching question asking the date that the symptoms were completely resolved. If patient answers yes to symptoms completely resolved, they will receive a branching question to input the date. Time from diagnosis to symptom resolution will be compared between the treatment groups. The branching question will appear on their text survey at any of the time points (days 1, 3, 7, 10, 14, 21, 28, 60) once they enter "yes" to symptoms completely resolved.
Secondary Change in medication compliance as determined by question in serial text survey Parents enter number of days patient has taken the medication in the past day as well as per day since the last survey in two questions on the text survey with their response being a drop down number list on the text survey- medication compliance will be compared to the number of doses that would be full compliance for that treatment arm days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)
Secondary Development of medication side effects as determined by question in serial text survey survey asks parents to describe any medication side effects they feel their child has had - descriptive outcome only days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)
Secondary Other medications taken as determined by question in serial text survey Parents are asked to list any medications in addition to their study drug and antibiotic that their child has taken- descriptive outcome only days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)
Secondary Fever as determined by question in serial text survey Parents are asked if their child had fever in the 24 hours prior to taking the text survey, duration of fever compared between treatment arms days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)
See also
  Status Clinical Trial Phase
Completed NCT04228458 - ThermRheum Version 1 N/A
Withdrawn NCT04976972 - A Comparison of Patients Receiving a Total Knee Replacement With Robotic Assistance or With Conventional Instrumentation N/A
Completed NCT04037436 - Functional Exercise and Nutrition Education Program for Older Adults N/A
Completed NCT00069342 - Health Beliefs and Health Behaviors Among Minorities With Rheumatic Diseases
Completed NCT02944448 - A Study Evaluating Pain Relief and Safety of Orally Administered CR845 in Patients With Osteoarthritis of Hip or Knee Phase 2
Recruiting NCT02498808 - Interferon-lambda: Novel Biologics for Controlling Neutrophil-mediated Pathology in Rheumatic Diseases? N/A
Recruiting NCT02777060 - Exploring the Effectiveness of Sensor-based Balance Training on Patient Outcome Measures N/A
Enrolling by invitation NCT02487888 - A Study of the Impact of Genetic Testing on Clinical Decision Making and Patient Care N/A
Withdrawn NCT02136251 - Total Shoulder Replacement Outcomes With Autologous Bone Graft as Fixator for Glenoid Anchor Peg.
Completed NCT02143206 - Modifying Exercise for the COPD Patient
Completed NCT01407874 - A Randomized, Double-Blind, Dose-Response Study of the Safety and Uric Acid Effects of Oral Ulodesine Added to Allopurinol in Subjects With Gout and Concomitant Moderate Renal Insufficiency Phase 2
Completed NCT01285843 - Periprosthetic Bone Mineral Density After Total Hip Arthroplasty Performed Through a Minimally Invasive Anterior Approach (AMIS) With Either an AMIStem or a Quadra Femoral Component N/A
Completed NCT01172327 - Self-Directed Exercise Program for Adults With Arthritis N/A
Completed NCT00987870 - Safety and Efficacy of BFH772 in Psoriasis Patients Phase 1/Phase 2
Completed NCT01184924 - Evaluation of the Arthritis Foundation Tai Chi Program N/A
Completed NCT00750984 - A Comparison of Two Different Surgical Techniques for Total Hip Resurfacing N/A
Active, not recruiting NCT00611585 - A Safety and Efficacy Study of the Birmingham Hip Resurfacing System N/A
Completed NCT00379184 - Sensitization in Osteoarthritic Knees N/A
Completed NCT00403676 - Nursing Consultation in Out-patient Clinics for Patients With Inflammatory Rheumatic Disease N/A
Completed NCT00175448 - Comparison of Physiotherapy Versus Home Exercise Following Hip Replacement Surgery N/A