Anti-Inflammatory Drug + Pain Challenge for Pain

Overseen By Alan R Prossin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Alan Prossin

Must not be taking: Anakinra

Disqualifiers: Severe illness, Depression, Anxiety, others

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

Compensation: Varies

Number of Visits: 5

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new anti-inflammatory drug, anakinra, might reduce pain during specific challenges. Researchers aim to determine if this drug affects pain levels and the body's natural pain-relief chemicals. The trial will compare the drug to a placebo during a pain test to understand its mechanism better. Individuals awaiting elective surgery without severe medical or mental health issues may be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that participants not be on any current medication treatment that would impact the measures of interest, so you may need to stop taking certain medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

An earlier study found anakinra to be generally safe. Researchers noticed fewer serious infections and no unusual increase in cancer cases. This suggests that anakinra is usually well-tolerated. However, as this study remains in its early stages, more detailed safety information is still being collected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about anakinra as a treatment for pain because it targets inflammation differently than standard pain medications. Unlike typical pain relievers, which might focus on blocking pain signals or reducing inflammation through broad mechanisms, anakinra specifically inhibits the interleukin-1 receptor. This targeted approach could potentially offer relief for inflammatory pain conditions with fewer side effects. Additionally, the use of a nociceptive pain challenge in this study allows researchers to better understand the pain pathways and the drug's effectiveness in real-time pain situations.

What evidence suggests that this trial's treatments could be effective for pain?

Research has shown that anakinra, a drug that reduces inflammation, effectively treats conditions like rheumatoid arthritis. It blocks a specific part of the immune system responsible for inflammation and pain. Studies have found that anakinra improves patient outcomes better than a placebo, though it may not be as effective as some other treatments, such as TNF-alpha blockers. In this trial, participants will receive either anakinra or a placebo, each combined with a nociceptive pain challenge, to test anakinra in a new pain condition. The aim is that by reducing inflammation, anakinra can also reduce pain. Early results in similar conditions suggest that anakinra has the potential to help manage pain through its anti-inflammatory effects. ^{1 4 6 7 8}

Who Is on the Research Team?

Alan R Prossin, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for healthy adults awaiting elective surgery, either obese or non-obese. They must not have had a PET scan in the past year, excessive lifetime radiation exposure, or any active severe medical conditions. Pregnant individuals or those with recent unprotected intercourse without contraception are excluded.

Inclusion Criteria

I am scheduled for a planned surgery.

My weight status is either obese or non-obese.

Negative urine pregnancy test

Exclusion Criteria

Recent (past year) PET scan(s)

You have used illegal drugs or abused alcohol in the past three months. However, if you use nicotine or drink alcohol in moderation, it's okay.

I do not have any severe mental or physical health conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experimental Pain Challenge

Participants undergo an experimental nociceptive pain challenge with mu-opioid receptor activity quantified via [11C]-carfentanil PET neuroimaging

1 week

1 visit (in-person)

Pharmacological Challenge

Participants receive anakinra or placebo to evaluate the effect on IL-1 cytokine activity and pain experience

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 to 8 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• anakinra
• Nociceptive pain challenge
• Placebo

Trial Overview The study aims to identify bio-signatures predicting pain and opioid neurotransmitter release during a controlled pain challenge. It will also test if an anti-inflammatory drug (minocycline) affects these bio-signatures and post-operative pain levels using [11C]-carfentanil PET neuroimaging.

How Is the Trial Designed?

Group I: Placebo plus nociceptive pain challenge, then anakinra plus nociceptive pain challenge Experimental Treatment 3 Interventions

Pharmacological challenge (with placebo) plus nociceptive pain challenge, then pharmacological challenge (with anakinra) plus nociceptive pain challenge

Group II: Anakinra plus nociceptive pain challenge, then placebo plus nociceptive pain challenge Experimental Treatment 3 Interventions

Pharmacological challenge (with anakinra) plus nociceptive pain challenge, then pharmacological challenge (with placebo) plus nociceptive pain challenge

Who Is Running the Clinical Trial?

Alan Prossin

Lead Sponsor

Trials

1

Recruited

70+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

A systematic review and meta-analysis of 27 randomized clinical trials involving various chronic pain conditions found no significant difference in assay sensitivity between average pain intensity (API) and worst pain intensity (WPI) as primary outcome measures.

This suggests that either API or WPI can be effectively used in clinical trials for assessing the efficacy of pain treatments, allowing researchers flexibility based on their study objectives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of the Assay Sensitivity of Average and Worst Pain Intensity in Pharmacologic Trials: An ACTTION Systematic Review and Meta-Analysis. Smith, SM., Jensen, MP., He, H., et al.[2019]

Recent advancements in understanding the mechanisms behind chronic non-malignant pain have improved therapeutic decision-making for managing conditions like back pain.

The chapter emphasizes the importance of randomized controlled trials in evaluating the effectiveness of treatments such as non-steroidal anti-inflammatory drugs, opioids, and co-analgesics, while also highlighting the need for long-term studies to assess drug efficacy, toxicity, and patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances with analgesics and NSAIDs for the treatment of spinal disorders. Desmeules, JA., Cedraschi, C., Piguet, V., et al.[2005]

The Reduction of Spontaneous Activity by Adjuvant (RSAA) model offers a new, unbiased method for testing analgesics by measuring increased locomotor activity in rats after administration of known pain relievers.

This model improves upon traditional pain assessment methods by using computer tracking to quantify movement, reducing rater interpretation errors and providing a more reliable evaluation of a drug's analgesic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locomotor activity in a novel environment as a test of inflammatory pain in rats. Matson, DJ., Broom, DC., Cortright, DN.[2022]

A comprehensive battery of human pain models, including electrical stimulation and cold pressor tasks, is essential for accurately assessing the analgesic effects of drugs, as no single model can fully replicate clinical pain.

These multi-modal pain tasks have been validated for reliability and predictive validity, allowing for efficient and repeated testing of drugs, particularly those with new or untested mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery. Hay, JL., Okkerse, P., van Amerongen, G., et al.[2018]

In a study of 25 healthy volunteers, both acetaminophen and the combination of acetaminophen with hydrocodone showed similar effectiveness in reducing perceived pain from a cold water stimulus, with decreases of 10.2% and 9.5% respectively.

Ibuprofen and placebo did not significantly reduce pain, indicating that in this noninflammatory pain model, the pain relief provided by acetaminophen and acetaminophen/hydrocodone was not distinguishable from each other, while mild side effects were reported in 44% of subjects taking acetaminophen/hydrocodone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized double-blind placebo controlled crossover study of acetaminophen, ibuprofen, acetaminophen/hydrocodone, and placebo for the relief of pain from a standard painful stimulus. Miner, JR.[2013]

Proof-of-concept (POC) clinical trials are crucial for assessing the potential efficacy of new and existing pain treatments, helping to determine whether they should proceed to larger confirmatory trials.

The IMMPACT consensus meeting highlighted the importance of efficient trial designs, such as adaptive and N-of-1 designs, to maximize statistical power while minimizing costs and participant exposure, ultimately aiming to improve the success rate of effective pain treatments in clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research designs for proof-of-concept chronic pain clinical trials: IMMPACT recommendations. Gewandter, JS., Dworkin, RH., Turk, DC., et al.[2023]

Emodin demonstrated significant anti-nociceptive effects in various pain models, effectively alleviating pain induced by both thermal and chemical stressors in mice, indicating its potential as a pain management alternative.

The study also confirmed emodin's strong anti-inflammatory properties, as shown by its ability to reduce inflammation in a carrageenan-induced model, while also noting a mild sedative effect on the treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emodin Reduces Inflammatory and Nociceptive Responses in Different Pain-and Inflammation-Induced Mouse Models. Zhang, X., Li, J., Guan, L.[2023]

Animal models of pain are crucial in drug discovery for chronic pain, helping researchers understand mechanisms and rank compounds, but their effectiveness in translating to human therapies has been questioned.

The chapter emphasizes the need for better study design and data interpretation in animal models, suggesting that current efficacy evaluations may be set too low, which could hinder successful clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Pharmacological Approaches in Drug Discovery for Chronic Pain. Whiteside, GT., Pomonis, JD., Kennedy, JD.[2016]

Preclinical procedures in analgesic drug development now include more clinically relevant pain models, such as those simulating inflammation or neuropathy, which help in understanding pain states like allodynia and hyperalgesia.

The incorporation of a wider range of pain-related behaviors, along with advanced imaging techniques like functional MRI, enhances the ability to assess the effects of analgesics and improves the predictive validity of drug development processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical assessment of candidate analgesic drugs: recent advances and future challenges. Negus, SS., Vanderah, TW., Brandt, MR., et al.[2016]

Citations

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Developing nociceptor-selective treatments for acute and ... This human cell/genetics-based approach can identify nociceptor-specific and pain-disease selective compounds that modulate the function of multiple targets.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1798177/

Observational study on efficacy, safety, and drug survival of ... The short term efficacy and safety profile of anakinra are comparable to those found in randomised clinical studies.

3. kineretrxhcp.com kineretrxhcp.com/difficult-to-treat/RA-efficacy.php

RA Efficacy - KINERET® (anakinra) Official HCP Website | Home Health outcomes were assessed by the Short Form-36 (SF-36) questionnaire. The 1-year data on HAQ in Study 1 showed more improvement with KINERET than placebo.

4. researchgate.net researchgate.net/publication/5531578_The_future_of_the_IL-1_receptor_antagonist_anakinra_From_rheumatoid_arthritis_to_adult-onset_still's_disease_and_systemic-onset_juvenile_idiopathic_arthritis

(PDF) The future of the IL-1 receptor antagonist anakinra In the treatment of patients with RA anakinra is effective but inferior to TNF-alpha blocking agents. Over the last few years it has become ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00121043

Evaluating Kineret® (Anakinra) in Rheumatoid Arthritis (RA ... In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2665913121000753

Challenges and opportunities of pharmacological ... The objective of this paper is to provide an overview of compounds under investigation for OA in phase II and III.

7. researchgate.net researchgate.net/publication/346707882_Safety_and_efficacy_of_anakinra_as_first-line_or_second-line_therapy_for_systemic_onset_juvenile_idiopathic_arthritis_-_data_from_the_German_BIKER_registry

Safety and efficacy of anakinra as first-line or second- ... Safety and efficacy of anakinra as first-line or second-line therapy for systemic onset juvenile idiopathic arthritis - data from the German ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6822819/

Towards an Effective and Safe Treatment of Inflammatory Pain The clinical management of inflammatory pain requires an optimal balance between effective analgesia and associated safety risks.