Anti-Inflammatory Drug + Pain Challenge for Pain
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Alan Prossin
Must not be taking: Anakinra
Disqualifiers: Severe illness, Depression, Anxiety, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The first objective of the study is to evaluate whether a novel bio-signature (derived from a wide range of pro- and anti-nociceptive IL-1 family cytokine activity) will predict pain experienced and also release of underlying endogenous opioid neurotransmitters during an experimental nociceptive pain challenge, which will be performed while simultaneously quantifying mu-opioid receptor activity in the brain via \[11C\]-carfentanil PET neuroimaging in healthy subjects. Another objective is to evaluate whether an anti-inflammatory drug that reduces activation of IL-1b (minocycline) will perturb the balance between pro- and anti-nociceptive IL-1 cytokines and effect a reduction in pain experienced (and endogenous opioids released) during the experimental, nociceptive pain challenge. A final objective is to evaluate performance characteristics (sensitivity, accuracy, dynamic range) of the biosignature for the purpose of predicting post-operative pain.
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.
What data supports the effectiveness of the drug anakinra (Kineret) for pain relief?
The research does not provide direct evidence for the effectiveness of anakinra (Kineret) in pain relief, but it discusses the importance of designing clinical trials to determine the efficacy of pain treatments. This suggests that well-designed trials are crucial for understanding the potential benefits of treatments like anakinra for pain.
12345How does the Anti-Inflammatory Drug + Pain Challenge differ from other pain treatments?
This treatment is unique because it combines an anti-inflammatory drug with a pain challenge, which may help better understand the drug's effects on pain through a comprehensive assessment of pain-related behaviors and responses. Unlike traditional methods, this approach uses a multi-modal pain task battery to evaluate the drug's analgesic (pain-relieving) effects, potentially offering a more complete picture of its effectiveness.
26789Eligibility Criteria
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.
+8 more
Trial Timeline
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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Placebo plus nociceptive pain challenge, then anakinra plus nociceptive pain challengeExperimental Treatment3 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 challengeExperimental Treatment3 Interventions
Pharmacological challenge (with anakinra) plus nociceptive pain challenge, then pharmacological challenge (with placebo) plus nociceptive pain challenge
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of Texas Health Science Center at HoustonHouston, TX
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Who Is Running the Clinical Trial?
Alan ProssinLead Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)Collaborator
References
Randomized double-blind placebo controlled crossover study of acetaminophen, ibuprofen, acetaminophen/hydrocodone, and placebo for the relief of pain from a standard painful stimulus. [2013]The objective was to compare subjects' change in perceived acute pain from an identical painful stimulus after receiving three separate, commonly used pain medications and placebo.
Research designs for proof-of-concept chronic pain clinical trials: IMMPACT recommendations. [2023]Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia, with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single-dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs, including N-of-1 designs, enriched designs, adaptive designs, and sequential parallel comparison designs, are summarized, and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.
A Comparison of the Assay Sensitivity of Average and Worst Pain Intensity in Pharmacologic Trials: An ACTTION Systematic Review and Meta-Analysis. [2019]Identifying methods to improve assay sensitivity in randomized clinical trials (RCTs) may facilitate the discovery of efficacious pain treatments. RCTs evaluating pain treatments typically use average pain intensity (API) or worst pain intensity (WPI) as the primary efficacy outcome. However, little evidence is available comparing the assay sensitivity of these 2 measures. In this systematic review and meta-analysis, we comprehensively reviewed all low back pain, osteoarthritis pain, fibromyalgia, diabetic peripheral neuropathy pain, and postherpetic neuralgia RCTs that used a parallel group design. Eligibility required: 1) primary RCT report published between 1980 and 2016, 2) comparing 1 or more active, efficacious pharmacologic pain treatment(s) with placebo, and 3) providing data on the standardized effect size (SES) for API as well as WPI for all treatment arms. Twenty-seven active versus placebo comparisons were identified in 23 eligible articles. Using a random-effects meta-analysis, API SES and WPI SES did not differ significantly (difference = -.021, 95% confidence interval = -.047 to .004, P = .12). The findings indicate that, depending on the objectives of the study, either API or WPI could be used as a primary outcome measure in clinical trials for the chronic pain conditions included in this analysis.
Emodin Reduces Inflammatory and Nociceptive Responses in Different Pain-and Inflammation-Induced Mouse Models. [2023]Different nociceptive models induced with heat and chemicals were used to assess the potency of emodin in alleviating pain. The anti-inflammatory properties of emodin at different doses were also assessed using different anti-inflammatory in vivo models.
Advances with analgesics and NSAIDs for the treatment of spinal disorders. [2005]One of the major developments with regard to chronic non-malignant pain in these last few years has been a better understanding of the mechanisms that act to maintain pain, while inferences about the pathophysiology have facilitated therapeutic decision-making. This chapter reviews the strength of evidence for the therapeutic effect of pharmacological symptomatic approaches using non-steroidal anti-inflammatory agents, opioids and co-analgesics in acute and chronic back pain with an emphasis on the results of randomized controlled trials as well as on the need for long-term comparative trials of drug efficacy, toxicity and compliance.
Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery. [2018]Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug's pharmacology and identify potentially suitable therapeutic populations. The need to use a comprehensive battery of pain models is highlighted by studies whereby only a single pain model, thought to relate to the clinical situation, demonstrates lack of efficacy. No single experimental model can mimic the complex nature of clinical pain. The integrated, multi-modal pain task battery presented here encompasses the electrical stimulation task, pressure stimulation task, cold pressor task, the UVB inflammatory model which includes a thermal task and a paradigm for inhibitory conditioned pain modulation. These human pain models have been tested for predicative validity and reliability both in their own right and in combination, and can be used repeatedly, quickly, in short succession, with minimum burden for the subject and with a modest quantity of equipment. This allows a drug to be fully characterized and profiled for analgesic effect which is especially useful for drugs with a novel or untested mechanism of action.
Locomotor activity in a novel environment as a test of inflammatory pain in rats. [2022]Creating a robust and unbiased assay for the study of current and novel analgesics has been a daunting task. Traditional rodent models of pain and inflammation typically rely on a negative reaction to various forms of evoked stimuli to elicit a pain response and are subject to rater interpretation. Recently, models such as weight bearing and gait analysis have been developed to address these drawbacks while detecting a drug's analgesic properties. We have recently developed the Reduction of Spontaneous Activity by Adjuvant (RSAA) model as a quick, unbiased method for the testing of potential analgesics. Rats, following prior administration of an activity-decreasing inflammatory insult, will positively increase spontaneous locomotor exploration when given single doses of known analgesics. The RSAA model capitalizes on a rat's spontaneous exploratory behavior in a novel environment with the aid of computer tracking software to quantify movement and eliminate rater bias.
Preclinical Pharmacological Approaches in Drug Discovery for Chronic Pain. [2016]In recent years, animal behavioral models, particularly those used in pain research, have been increasingly scrutinized and criticized for their role in the poor translation of novel pharmacotherapies for chronic pain. This chapter addresses the use of animal models of pain used in drug discovery research. It highlights how, when, and why animal models of pain are used as one of the many experimental tools used to gain better understanding of target mechanisms and rank-order compounds in the iterative process of establishing structure-activity relationship. Together, these models help create an "analgesic signature" for a compound and inform the indications most likely to yield success in clinical trials. In addition, the authors discuss some often underappreciated aspects of currently used (traditional) animal models of pain, including simply applying basic pharmacological principles to study design and data interpretation as well as consideration of efficacy alongside side effect measures as part of the overall conclusion of efficacy. This is provided to add perspective regarding current efforts to develop new models and endpoints both in rodents and in larger animal species as well as assess cognitive and/or affective aspects of pain. Finally, the authors suggest ways in which efficacy evaluation in animal models of pain, whether traditional or new, might better align with clinical standards of analysis, citing examples where applying effect size and number needed to treat estimations to animal model data suggest that the efficacy bar often may be set too low preclinically to allow successful translation to the clinical setting.
Preclinical assessment of candidate analgesic drugs: recent advances and future challenges. [2016]In analgesic drug development, preclinical procedures are widely used to assess drug effects on pain-related behaviors. These procedures share two principal components: 1) a manipulation intended to produce a pain-like state in the experimental subject and 2) measurement of behaviors presumably indicative of that pain state. Drugs can then be evaluated for their ability to attenuate pain-related behaviors. In the simplest procedures, the pain state is produced by delivery of an acute noxious stimulus (e.g., a warm thermal stimulus), and the primary dependent measures focus on withdrawal responses or other nocifensive behaviors that increase in rate, frequency, or intensity in response to the noxious stimulus. This approach has been refined in two ways. First, new methods have been developed to induce more clinically relevant pain states. In particular, pain requiring clinical intervention is often associated with inflammation or neuropathy, and novel procedures have emerged to model these conditions and their ability to produce hypersensitive pain states, such as allodynia and hyperalgesia. Second, studies are incorporating a broader array of pain-related behaviors as dependent measures. For example, pain not only stimulates nocifensive behaviors but also suppresses many adaptive behaviors, such as feeding or locomotion. Measures of pain-suppressed behaviors can provide new insights into the behavioral consequences of pain and the effects of candidate analgesics. In addition, functional magnetic resonance imaging has emerged as a noninvasive tool for investigating changes in neural activity associated with pain and analgesia. Integration of these complementary approaches may improve the predictive validity of analgesic drug development.