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Symptomatic Management of Lyme Arthritis

Primary Purpose

Lyme Arthritis, Lyme Disease, Arthritis

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Naproxen
Acetaminophen
Sponsored by
Desiree Neville, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lyme Arthritis focused on measuring Lyme Arthritis, Lyme, Lyme Disease, Arthritis, NSAID

Eligibility Criteria

3 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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  • Patients will be secondarily withdrawn from analysis and instructed to stop study medication if their Lyme test is negative.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

Sites / Locations

  • Children's Hospital of Pittsburgh of UPMCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

No Intervention

Arm Label

NSAID

Acetaminophen

NSAID first, then Acetaminophen

Standard Care

Arm Description

Naproxen at weight based standard dose given bid daily until symptoms resolve

Acetaminophen at weight based standard dose given qid until symptoms resolve

Naproxen at weight based standard dose given bid for one week, then acetaminophen at weight based standard dose given qid until symptoms resolve

Symptom observation only

Outcomes

Primary Outcome Measures

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
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
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
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
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.

Secondary Outcome Measures

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
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
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
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

Full Information

First Posted
July 15, 2019
Last Updated
December 2, 2022
Sponsor
Desiree Neville, MD
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1. Study Identification

Unique Protocol Identification Number
NCT04038346
Brief Title
Symptomatic Management of Lyme Arthritis
Official Title
Symptomatic Management of Lyme Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Desiree Neville, MD

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed Description
Specific Aims: Demonstrate feasibility to ensure adequate patient enrollment and symptomatic follow-up of patients with Lyme arthritis. 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. Quantification of antibiotic-refractory Lyme arthritis in our population 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) Assess side effects of patients with Lyme arthritis placed on scheduled NSAIDs versus those not placed on scheduled NSAIDs 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lyme Arthritis, Lyme Disease, Arthritis
Keywords
Lyme Arthritis, Lyme, Lyme Disease, Arthritis, NSAID

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Prospective, randomized, controlled, non blinded
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NSAID
Arm Type
Experimental
Arm Description
Naproxen at weight based standard dose given bid daily until symptoms resolve
Arm Title
Acetaminophen
Arm Type
Active Comparator
Arm Description
Acetaminophen at weight based standard dose given qid until symptoms resolve
Arm Title
NSAID first, then Acetaminophen
Arm Type
Experimental
Arm Description
Naproxen at weight based standard dose given bid for one week, then acetaminophen at weight based standard dose given qid until symptoms resolve
Arm Title
Standard Care
Arm Type
No Intervention
Arm Description
Symptom observation only
Intervention Type
Drug
Intervention Name(s)
Naproxen
Other Intervention Name(s)
naprosyn, aleve, anaprox
Intervention Description
Patients will be randomized to an NSAID (naproxen)
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Other Intervention Name(s)
tylenol
Intervention Description
Patients will be randomized to acetaminophen
Primary Outcome Measure Information:
Title
Change in the degree of joint pain determined by serial visual analog scale for pain via text surveys
Description
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
Time Frame
days 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected, time to symptom resolution will be recorded
Title
Change in the degree of joint redness determined by serial visual analog scale for joint redness via text surveys
Description
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
Time Frame
days 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected, time to symptom resolution will be recorded
Title
Change in degree of joint movement determined by serial visual analog scale for joint movement via text surveys
Description
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
Time Frame
days 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected, time to symptom resolution will be recorded
Title
Change in degree of overall function determined by serial visual analog scale for overall function via text surveys
Description
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
Time Frame
days 1, 3, 7, 10, 14, 21, 28, 60 the VAS score will be collected, time to symptom resolution will be recorded
Title
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.
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Change in medication compliance as determined by question in serial text survey
Description
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
Time Frame
days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)
Title
Development of medication side effects as determined by question in serial text survey
Description
survey asks parents to describe any medication side effects they feel their child has had - descriptive outcome only
Time Frame
days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)
Title
Other medications taken as determined by question in serial text survey
Description
Parents are asked to list any medications in addition to their study drug and antibiotic that their child has taken- descriptive outcome only
Time Frame
days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)
Title
Fever as determined by question in serial text survey
Description
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
Time Frame
days 1, 3, 7, 10, 14, 21, 28, 60 (collected until symptom resolution)
Other Pre-specified Outcome Measures:
Title
Need for further care as determined by medical record review as number of visits in the system for Lyme arthritis symptoms
Description
Mean repeat medical visits for Lyme arthritis will be compared between treatment arms based on medical record review
Time Frame
30 days, 60 days, 120 days, 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Desiree NW Neville, MD
Phone
412-692-7692
Email
desiree.neville@chp.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Desiree NW Neville, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neville, MD
Email
desiree.neville@chp.edu
First Name & Middle Initial & Last Name & Degree
Desiree Neville, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Symptomatic Management of Lyme Arthritis

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