NSAIDs for Lyme Arthritis

Overseen By Desiree NW Neville, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Desiree Neville, MD

Must not be taking: Daily NSAIDs, Daily acetaminophen

Disqualifiers: Rheumatoid arthritis, Kidney impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing if taking anti-inflammatory drugs regularly can help prevent long-term joint problems in people with Lyme disease. It focuses on patients who don't get better with antibiotics. The drugs work by reducing inflammation, which might stop the prolonged symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are already taking daily NSAIDs or acetaminophen, you cannot participate. If you have any hypersensitivity to naproxen or acetaminophen, you should not take the study medications.

Is naproxen sodium safe for general use?

Naproxen sodium is generally safe for over-the-counter use, with most people experiencing no adverse effects. Common side effects include headache, nausea, and drowsiness, but these occur at similar rates to a placebo. However, it can cause stomach issues, allergic reactions, and liver problems, and should be avoided by people with heart failure or high blood pressure. ^{1 2 3 4 5}

How does the drug Acetaminophen and Naproxen differ from other treatments for Lyme Arthritis?

Acetaminophen and Naproxen are used for their pain-relieving and anti-inflammatory effects, with Naproxen being a nonsteroidal anti-inflammatory drug (NSAID) that reduces inflammation and pain, while Acetaminophen primarily relieves pain and reduces fever. This combination may offer a balanced approach to managing symptoms of Lyme Arthritis, especially for patients who cannot tolerate other anti-inflammatory drugs like aspirin. ^{6 7 8 9 10}

What evidence supports the effectiveness of the drug naproxen for treating Lyme arthritis?

Research shows that naproxen, a type of anti-inflammatory drug, is effective in relieving pain for conditions like rheumatoid arthritis, which is similar to Lyme arthritis. It was found to provide significant pain relief and was preferred by patients in studies comparing it to other pain relievers. ^{8 11 12 13 14}

Who Is on the Research Team?

Desiree NW Neville, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for individuals with Lyme arthritis who are testing positive for Lyme disease. It's not suitable for those with rheumatoid or recurrent arthritis, on daily NSAIDs or acetaminophen, have severe liver issues, a history of allergic reactions to NSAIDs, or underlying kidney or liver impairment.

Inclusion Criteria

Undergoing Lyme disease testing (Lyme test positive)

I have arthritis.

Exclusion Criteria

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

I am allergic to naproxen, aspirin, or have had bad reactions to NSAIDs.

I am allergic to acetaminophen or have severe liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive scheduled NSAIDs, acetaminophen, or NSAIDs followed by acetaminophen to manage Lyme arthritis symptoms

8 weeks

Regular text surveys on days 1, 3, 7, 10, 14, 21, 28, 60

Follow-up

Participants are monitored for safety and effectiveness after treatment, including symptom resolution and side effects

4 weeks

Follow-up visits as needed based on symptom resolution

Long-term Follow-up

Participants' need for further care and medication compliance are assessed over an extended period

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Acetaminophen
• Naproxen

Trial Overview The study tests if scheduled use of the anti-inflammatory drug Naproxen, pain reliever Acetaminophen, or a combination can prevent prolonged symptoms in Lyme arthritis. Patients will be randomly assigned to one of these treatments and monitored for symptom duration and treatment side effects.

How Is the Trial Designed?

Group I: NSAID first, then Acetaminophen Experimental Treatment 2 Interventions

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

Group II: NSAID Experimental Treatment 1 Intervention

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

Group III: Standard Care Active Control 1 Intervention

Symptom observation only

Group IV: Acetaminophen Active Control 1 Intervention

Acetaminophen at weight based standard dose given qid until symptoms resolve

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

Approved in United States as Tylenol for:

• Pain relief
• Fever reduction

Approved in European Union as Paracetamol for:

• Pain relief
• Fever reduction

Approved in Canada as Tylenol for:

• Pain relief
• Fever reduction

Who Is Running the Clinical Trial?

Desiree Neville, MD

Lead Sponsor

Trials

1

Recruited

300+

Published Research Related to This Trial

A variety of antirheumatic drugs are available for treating rheumatic diseases, with aspirin being the preferred choice for anti-inflammatory activity in early stages, while alternatives like phenylpropionic acid derivatives are recommended for those who cannot tolerate salicylates.

As the disease progresses, if nonsteroidal anti-inflammatory drugs are ineffective, treatments may escalate to gold compounds or penicillamine, with corticosteroids and immunosuppressives reserved for severe cases or those with significant side effects from other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug therapy reviews: antirheumatic agents. Evens, RP.[2013]

Flurbiprofen has been proven safe and effective as an analgesic, anti-inflammatory, and antipyretic agent in numerous European clinical trials over the past 12 years, showing it is at least as potent as indomethacin and significantly more potent than aspirin.

In patients with rheumatoid arthritis and ankylosing spondylitis, flurbiprofen demonstrated superior or equivalent efficacy compared to other common treatments like aspirin, naproxen, and indomethacin, with minimal gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience with flurbiprofen. A new analgesic/anti-inflammatory agent. Buchanan, WW., Kassam, YB.[2022]

In a double-blind trial involving rheumatoid arthritis patients, both benoxaprofen and naproxen were effective anti-inflammatory drugs, with no significant difference in overall efficacy between the two.

While naproxen showed a slight advantage in improving grip strength, both medications had mild and infrequent side effects, indicating a good safety profile for both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative trial of benoxaprofen and naproxen. Highton, J., Grahame, R.[2019]

In a study involving 90 patients with rheumatoid arthritis, diclofenac, indomethacin, naproxen, and tolfenamic acid were found to provide the greatest pain relief and were preferred by most patients.

These four drugs were significantly more effective (p < 0.01) than the least effective options, ketoprofen and proquazone, while acetylsalicylic acid, azapropazone, carprofen, and ibuprofen showed intermediate efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the analgesic effect of ten nonsteroidal anti-inflammatory drugs. Isomäki, H., Martio, J., Kaarela, K., et al.[2019]

A systematic review of 12 clinical trials and 1 observational study on paracetamol for inflammatory arthritis found weak evidence supporting its effectiveness over placebo, particularly in patients with rheumatoid arthritis.

While paracetamol may provide some additive benefit when used with NSAIDs, its safety profile remains uncertain, with one study suggesting a higher risk of serious gastrointestinal events when used alongside corticosteroids and other analgesics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paracetamol for the management of pain in inflammatory arthritis: a systematic literature review. Hazlewood, G., van der Heijde, DM., Bombardier, C.[2018]

A comprehensive evaluation of naproxen sodium's safety involved 48 clinical trials with 4138 participants, showing that 83% of patients reported no adverse events, indicating a favorable safety profile for over-the-counter use.

The incidence of adverse events was similar between naproxen sodium and placebo, with common side effects like headache and nausea occurring at comparable rates, suggesting that naproxen sodium is as safe as other common over-the-counter pain relievers like ibuprofen and acetaminophen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of over-the-counter naproxen sodium. DeArmond, B., Francisco, CA., Lin, JS., et al.[2019]

Naproxen sodium is effective for pain relief, reducing fever, and decreasing inflammation, but it can cause gastrointestinal issues and allergic reactions, and may lead to liver damage in some cases.

It is not recommended for individuals with certain health conditions, such as heart failure or hypertension, and is comparable in effectiveness to other over-the-counter pain relievers like ibuprofen and acetaminophen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen sodium. Sutton, LB.[2019]

In a 12-month study involving 600 patients, sumatriptan-naproxen sodium was found to be well tolerated for treating moderate to severe migraines, with 94% of participants receiving treatment for at least one migraine attack.

The most common side effects were nausea, muscle tightness, and dizziness, but serious adverse events were rare, with only one possibly related to the treatment, indicating a favorable safety profile for this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twelve-month tolerability and safety of sumatriptan-naproxen sodium for the treatment of acute migraine. Winner, P., Cady, RK., Ruoff, GE., et al.[2013]

Naproxen and naproxen sodium are effective non-steroidal anti-inflammatory drugs (NSAIDs) with various indications, but they can cause adverse reactions affecting the gastrointestinal tract, central nervous system, kidneys, liver, and blood.

Recent studies raise questions about the safety and recommendations for using these drugs, particularly in vulnerable populations like the elderly and pregnant women, highlighting the need for cautious prescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naproxen: pharmacology and dental therapeutics. Roda, RS.[2022]

In a study of 57 malaria patients, the combination of Artemisinin-Based Combination Therapies (ACTs) with paracetamol significantly altered 24 out of 37 evaluated toxicity markers, indicating potential safety concerns with this treatment regimen.

The findings suggest that careful selection of ACTs plus paracetamol is crucial, especially for patients with existing health conditions, due to the observed changes in various biochemical and haematological indices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicological effect of Artemisinin-Based Combination Therapies plus Paracetamol in malaria patients. Aghahowa, SE., Ozolua, RI., Bafor, EE., et al.[2023]

In a trial involving 25 patients, both Naprosyn (naproxen) and Butacote (phenylbutazone) significantly reduced morning stiffness, pain, and discomfort, showing their efficacy in treating inflammatory conditions.

While both medications had similar objective effects, patients and physicians preferred Butacote based on subjective assessments, although the difference was not statistically significant, and side effects were mostly minor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of Butacote and Naprosyn in ankylosing spondylitis. Ansell, BM., Major, G., Liyanage, SP., et al.[2019]

Dipyrone, an analgesic used globally, works primarily through its metabolite 4-methyl-amino-antipyrine (MAA), which effectively inhibits both COX-1 and COX-2 enzymes, providing significant pain relief for at least 8 to 12 hours after administration.

The study found that dipyrone's inhibition of COX-2 is much stronger than that of other common analgesics like celecoxib and rofecoxib, suggesting that its pain-relieving effects are largely due to peripheral mechanisms, while its lower gastrointestinal side effects may be due to its non-acidic nature rather than selective COX-1 inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dipyrone elicits substantial inhibition of peripheral cyclooxygenases in humans: new insights into the pharmacology of an old analgesic. Hinz, B., Cheremina, O., Bachmakov, J., et al.[2015]

Paracetamol and dipyrone both effectively reduced pain in a rat model of inflammatory pain, with paracetamol also increasing pain thresholds in non-inflamed areas, indicating a broader analgesic effect.

The analgesic mechanisms of paracetamol and dipyrone differ; paracetamol's effects can be reversed by the opioid antagonist naltrexone, while dipyrone's analgesia is not affected by naltrexone, suggesting distinct pathways for their pain-relieving actions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different mechanisms underlie the analgesic actions of paracetamol and dipyrone in a rat model of inflammatory pain. Rezende, RM., França, DS., Menezes, GB., et al.[2018]

The review of 13 randomized-controlled trials on NSAIDs and paracetamol for cancer pain management indicates that their role remains controversial, with no clear evidence supporting their use as initial treatments alongside opioids.

While paracetamol appears to offer little benefit at standard doses, ketorolac may provide an additional analgesic effect when used with opioids, suggesting that NSAIDs could be beneficial for some patients in managing cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long and winding road of non steroidal antinflammatory drugs and paracetamol in cancer pain management: a critical review. Mercadante, S., Giarratano, A.[2018]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Drug therapy reviews: antirheumatic agents. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

European experience with flurbiprofen. A new analgesic/anti-inflammatory agent. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A comparative trial of benoxaprofen and naproxen. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Comparison of the analgesic effect of ten nonsteroidal anti-inflammatory drugs. [2019]

5. Canada pubmed.ncbi.nlm.nih.gov

Paracetamol for the management of pain in inflammatory arthritis: a systematic literature review. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Safety profile of over-the-counter naproxen sodium. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Naproxen sodium. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Twelve-month tolerability and safety of sumatriptan-naproxen sodium for the treatment of acute migraine. [2013]

9. Canada pubmed.ncbi.nlm.nih.gov

Naproxen: pharmacology and dental therapeutics. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Toxicological effect of Artemisinin-Based Combination Therapies plus Paracetamol in malaria patients. [2023]

11. England pubmed.ncbi.nlm.nih.gov

A comparative study of Butacote and Naprosyn in ankylosing spondylitis. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Dipyrone elicits substantial inhibition of peripheral cyclooxygenases in humans: new insights into the pharmacology of an old analgesic. [2015]

13. England pubmed.ncbi.nlm.nih.gov

Different mechanisms underlie the analgesic actions of paracetamol and dipyrone in a rat model of inflammatory pain. [2018]

14. Netherlands pubmed.ncbi.nlm.nih.gov

The long and winding road of non steroidal antinflammatory drugs and paracetamol in cancer pain management: a critical review. [2018]