Placebo for Pain Management
(WASABI Trial)
Recruiting in Palo Alto (17 mi)
Overseen byTor D Wager, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Trustees of Dartmouth College
Must not be taking: Antidepressants, Mood stabilizers, Opiates, others
Disqualifiers: Cancer, Cardiovascular disease, Neurological disorders, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This functional magnetic-resonance imaging study of the brain will feature a within-subject crossover design to investigate the effects of a placebo cream on painful thermal stimulation rendered upon eight body sites. The investigators aim to 1.) improve the understanding of how the brain represents thermal pain responses somatotopically (i.e., across different body-sites) 2.) to test these brain representations with and without the presence of a pain-targeted placebo intervention, and 3.) to examine how these brain representations change prior to vs. during the delivery of thermal pain. They predict that placebo cream will downregulate the intensity of aversive brain activity representations, and to a lesser degree, sensation and somatotopic representations, both prior to and during painful thermal stimulation.
Will I have to stop taking my current medications?
The trial requires that participants have not been treated with certain medications like antidepressants, mood stabilizers, glucocorticoids, opiates, antipsychotics, and some others within the last month. If you are currently taking these, you may need to stop before participating.
Is the placebo cream safe for use in humans?
A small survey of prescribing providers found that topical compounded pain creams, which include placebo creams, were considered safe for patients. These creams are commonly used for musculoskeletal and neuropathic pain, and prescribers felt they were a safe alternative to narcotics.
12345How does the placebo treatment for pain management differ from other treatments?
The placebo treatment for pain management is unique because it relies on the psychological effect of believing in the treatment rather than active ingredients, and it can be enhanced by giving patients control over when they receive it, which can increase its effectiveness and duration.
13678Eligibility Criteria
This study is for volunteers over 18, with no history of pathological pain or chronic conditions, who can tolerate heat on their forearm. They must not be pregnant, have metal in their body, suffer from severe cardiovascular issues or neurological disorders, smoke heavily, use alcohol frequently, or have had recent psychoactive substance abuse.Inclusion Criteria
You should not have any current or recent history of severe pain.
Subject must be able to read and speak English
Subject must be a volunteer with a minimum age of 18 years and must be able and willing to provide written informed consent
+5 more
Exclusion Criteria
You have metal in your body or have worked with metal fragments in the past (like as a machinist).
You cannot handle heat pain applied to your forearm.
If female, pregnancy
+33 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
fMRI Scanning - Sensation and Aversiveness
Participants undergo fMRI scanning to isolate sensation, aversiveness, and somatotopic subcomponents of pain using thermal and auditory stimuli.
1 hour
1 visit (in-person)
fMRI Scanning - Placebo Treatment
Participants undergo fMRI scanning to examine the response of isolated subcomponents to placebo treatment for heat pain.
1 hour
1 visit (in-person)
Follow-up
Participants are monitored for any delayed effects or adverse reactions post-treatment.
2-4 weeks
Participant Groups
The trial tests the effects of a placebo cream on brain activity during painful heat exposure to different body sites using fMRI scans. It aims to see if the placebo alters how the brain processes and anticipates pain before and during thermal stimulation.
2Treatment groups
Experimental Treatment
Group I: Placebo Cream firstExperimental Treatment2 Interventions
Each participant will undergo thermal pain tasks after being administered a "treatment" cream to one of eight body sites.
Group II: Control Cream firstExperimental Treatment2 Interventions
Each participant will undergo thermal pain tasks after being administered a "control" cream to one of eight body sites.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dartmouth CollegeHanover, NH
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Who Is Running the Clinical Trial?
Trustees of Dartmouth CollegeLead Sponsor
References
Instrumental Control Enhances Placebo Analgesia. [2020]Placebo analgesia is a robust phenomenon readily observed in both experimental and clinical settings. While researchers have begun to unpack its psychobiological mechanisms, important questions remain regarding how we can capitalize on the placebo effect to improve clinical pain outcomes. The current study tested whether providing individuals with instrumental control-that is, control over if and when they administer a treatment-is capable of enhancing placebo analgesia. Using an established electrocutaneous pain design, 87 healthy volunteers either received placebo conditioning with instrumental control over treatment administration, standard passive placebo conditioning without any control over treatment administration, or were allocated to natural history control group with no conditioning and were later tested at equivalent shock intensity with and without placebo applied. Both placebo groups demonstrated initial placebo analgesia. Importantly, however, those provided with instrumental control demonstrated significantly larger and longer lasting placebo analgesia as well as reduced anticipatory autonomic arousal than those receiving standard passive placebo conditioning. This suggests that providing instrumental control over treatment administration can facilitate placebo analgesia by enhancing its magnitude and durability. As such, providing instrumental control over treatment administration may be a cheap and ethical method of using the placebo effect to improve clinical pain outcomes. PERSPECTIVE: Placebo research typically involves passive designs where individuals have no control over treatment administration. We present novel data demonstrating that providing control over treatment administration substantially enhances both the magnitude and duration of placebo analgesia. As such, where possible, providing control may improve clinical pain outcomes via the placebo effect.
Placebo interventions for all clinical conditions. [2022]Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published.
A brief survey on prescriber beliefs regarding compounded topical pain medications. [2015]Pain is extremely common in the U.S. It is estimated that 116 million Americans suffer from chronic pain. Narcotics and opioid medications are heavily relied upon for the treatment of pain. Currently, there is an epidemic of opioid abuse and misuse in the U.S. and alternative methods for the treatment of pain are required. Topical compounded pain creams are thought to be one such alternative. The purpose of this study was to establish a baseline regarding the beliefs of community physicians on the safety and efficacy of these compounds. A survey was sent to practicing physicians in the U.S. regarding their prescribing behaviors for topical compounds, as well as their beliefs about the efficacy and safety of these medications. Eleven prescribing practitioners participated in this survey with a response rate of 78%. The results were compiled with basic statistical work (Excel). This survey demonstrated that at the time of the study, topical compound creams for the treatment of pain were commonly used in clinical practice; these creams were used for musculoskeletal pain and for neuropathic pain. It was also determined that the vast majority of practicing prescribers felt that compounded pain creams were more efficacious than mass-produced, U.S. Food and Drug Administration-approved creams marketed by large multi-national pharmaceutical companies. Most of the respondents felt that these compounds allowed them to reduce their narcotic prescriptions overall. In addition, the results demonstrated that the prescribers felt these compounds were safe for their patients. In this small survey of practicing prescribing providers regarding the use of topical compounds, we found that these medications were not only effective but also safe.
Topical treatment in pain medicine: from ancient remedies to modern usage. [2015]Over several millennia, substances have been applied to the skin for treatment of pain. Some ingredients are in current use; others have been discontinued. Mechanisms of action include interactions with nociceptive neural networks and inflammatory processes. Substances must penetrate the stratum corneum barrier and vehicles that enhance penetration have been developed. Topical drugs with links to the past include menthol, capsaicin, some opioids, local anesthetic agents and NSAIDs. Mandragora is also described as an example of a herbal remedy that has been discontinued due to its toxicity. The future for topical drugs is promising, with the advent of new drugs tailored for specific pain mechanisms and the development of both penetration enhancers and sterile preparation methods.
Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics. [2021]Treatment of neuropathic pain using topical formulations is still in its infancy. Only few topical analgesic formulations have become available for clinical use, and among these, analgesic creams are still rare. This is unfortunate because analgesic creams offer a number of advantages over patches, such as convenience, ease of adapting the frequency of application, and dose, and "rubbing cream where it hurts" involves the patient much more in the therapeutic process compared to patches and other localized treatment modalities. Although the literature supporting the efficacy and safety of analgesic creams (mostly compounded) is growing since the last decade, most pain physicians have not yet noticed and appreciated the therapeutic potential and clinical value of these creams. This is most probably due to a prejudice that topical application should need to act transdermally, more or less as a slow-release formulation, such as in patches delivering opioids. We will discuss this prejudice and show that there are multiple important targets in the skin to be reached by topical analgesic or anti-inflammatory compounds, and that the keratinocyte is one of those targets. By specifically targeting the keratinocyte, analgesia seems possible, effective, and safe, and thus topical analgesic creams may hold promise as a novel treatment modality for neuropathic pain.
Topical anaesthesia for venepuncture. [2019]A topical anaesthetic cream was tested in a randomised, double blind, placebo controlled trial of 15 children. The severity of pain experienced during venepuncture was assessed, using visual analogue and verbal rating scales. The topical anaesthetic cream was found to be significantly superior to placebo using each form of assessment.
Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain. [2022]Pharmacologic treatment of chronic pain is challenging. Oral therapy may require multiple medications; each has side effects, dose limitations, and limited efficacy. Compounded topical formulations have evolved as potential treatment options. The objective of this study was to evaluate the efficacy of 2 compounded topical creams, "Cream I" and "Cream II," in patients with chronic extremity, joint, musculoskeletal, neuropathic, or other chronic topical pain conditions and compare their efficacy with Voltaren gel. The primary efficacy outcome was the change in visual numeric pain intensity score from pretreatment to posttreatment. The Cream I contained Flurbiprofen (20%), Tramadol (5%), Clonidine (0.2%), Cyclobenzaprine (4%), and Bupivacaine (3%). The Cream II contained Flurbiprofen (20%), Baclofen (2%), Clonidine (0.2%), Gabapentin (10%), and Lidocaine (5%). The Voltaren gel contained 1% diclofenac sodium. A total of 2177 patients were evaluated, 826 males and 1351 females. During their medical treatment, 1141 patients received Cream I, 527 patients received Cream II, and 509 patients received Voltaren gel. After treatment, the pain intensity score decreased by 3.11 ± 1.65 (37%) with Cream I (from 8.44 ± 1.19 to 5.33 ± 2.0, P
Placebo analgesia is not due to compliance or habituation: EEG and behavioural evidence. [2007]This study was designed to resolve whether experimental placebo responses are due to either increased compliance or habituation. We stimulated both forearms and recorded laser-evoked potentials from 18 healthy volunteers treated on one arm with a sham analgesic cream and an inactive cream on the other (treatment group), and 13 volunteers with an inactive cream on both arms (controls). The treatment group showed a significant reduction in the pain ratings and laser-evoked potentials with both the sham and inactive creams. The control group showed no evidence of habituation to the laser stimulus. The results indicate that the reduction in pain during experimental placebo response is unlikely to be due to sensory habituation or compliance with the experimental instructions.