Placebo for Pain Management

(WASABI Trial)

Overseen By Tor D Wager, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Trustees of Dartmouth College

Must not be taking: Antidepressants, Mood stabilizers, Opiates, others

Disqualifiers: Cancer, Cardiovascular disease, Neurological disorders, others

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

Compensation: Varies

Number of Visits: 2

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a placebo cream affects the brain's response to heat-induced pain on different body parts. Researchers aim to determine if the placebo can alter how the brain processes and perceives pain before and during heat application. Participants will use both a placebo cream and a control cream to compare their effects. Individuals who do not currently experience pain and can tolerate mild heat on their skin might be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to the scientific understanding of pain perception and placebo effects.

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.

What prior data suggests that this placebo cream is safe for pain management?

Research has shown that placebo treatments, such as the placebo cream in this study, are generally safe. Because placebos lack active medical ingredients, they usually do not cause side effects. This study aims to observe how a placebo cream might alter brain responses to pain. Since the placebo cream contains no active substances, participants are expected to tolerate it well.

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the power of placebo effects in pain management, offering a potential alternative to conventional painkillers like opioids and NSAIDs. Unlike these standard treatments, which often come with significant side effects and addiction risks, the placebo cream aims to tap into the mind's ability to alleviate pain without active pharmacological ingredients. By understanding how placebo effects can be harnessed, this approach could lead to safer pain management options that reduce reliance on traditional medications.

What evidence suggests that this placebo cream is effective for pain management?

Research has shown that placebos can sometimes help reduce pain. In past studies, participants who received a placebo reported feeling less pain, even though the placebo contained no active medicine. This occurs because the brain believes the treatment is real and reacts accordingly. The placebo effect can lead to a sensation of relief. In this trial, participants will receive either a placebo cream or a control cream, neither containing pain-relieving ingredients, but they might still help lessen pain due to these brain changes.

Who Is on the Research Team?

Tor D Wager, PhD

Principal Investigator

Dartmouth College

Are You a Good Fit for This Trial?

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.

If female, the subject must be non-lactating, not pregnant, and using a reliable contraception method

Subject must be able to understand and follow the instructions of the investigator and understand all screening questionnaires

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Control Cream
• Placebo Cream

Trial Overview 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.

How Is the Trial Designed?

Group I: Placebo Cream first Experimental Treatment 2 Interventions

Each participant will undergo thermal pain tasks after being administered a "treatment" cream to one of eight body sites.

Group II: Control Cream first Experimental Treatment 2 Interventions

Each participant will undergo thermal pain tasks after being administered a "control" cream to one of eight body sites.

Who Is Running the Clinical Trial?

Trustees of Dartmouth College

Lead Sponsor

Trials

32

Recruited

14,500+

Published Research Related to This Trial

In a randomized, double-blind, placebo-controlled trial involving 15 children, a topical anesthetic cream significantly reduced pain during venepuncture compared to a placebo.

The effectiveness of the topical anesthetic was confirmed through both visual analogue and verbal rating scales, indicating its reliable pain-relief properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical anaesthesia for venepuncture. Clarke, S., Radford, M.[2019]

A systematic review of 234 randomized placebo trials involving 10,525 patients found that placebo interventions generally do not have clinically important effects across various health conditions, with a pooled effect size indicating minimal benefit.

However, placebo interventions showed some influence on patient-reported outcomes, particularly for pain and nausea, although the effects varied widely and were often difficult to separate from reporting biases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo interventions for all clinical conditions. Hróbjartsson, A., Gøtzsche, PC.[2022]

Topical treatments for pain have a long history, utilizing various substances like menthol and capsaicin, which work by interacting with pain-sensing nerves and reducing inflammation.

The future of topical pain relief looks bright, with new drugs being developed to target specific pain mechanisms and improved methods for enhancing skin penetration and ensuring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical treatment in pain medicine: from ancient remedies to modern usage. Finch, PM., Drummond, PD.[2015]

In a study involving 18 healthy volunteers, the use of a sham analgesic cream led to a significant reduction in pain ratings and laser-evoked potentials, suggesting that placebo responses can effectively reduce perceived pain.

The findings indicate that the observed placebo effects are not due to sensory habituation or compliance, as the control group (13 volunteers) showed no change in pain response, highlighting the genuine impact of placebo treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo analgesia is not due to compliance or habituation: EEG and behavioural evidence. Watson, A., El-Deredy, W., Vogt, BA., et al.[2007]

In a study involving 2177 patients with various chronic pain conditions, two compounded topical creams (Cream I and Cream II) significantly reduced pain intensity scores by 37% and 35%, respectively, compared to a 19% reduction with Voltaren gel.

Both Cream I and Cream II were found to be more effective than Voltaren gel, suggesting that compounded topical formulations may offer better pain relief options for patients with chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain. Somberg, JC., Molnar, J.[2022]

Topical analgesic creams for neuropathic pain are underutilized despite their advantages over patches, such as ease of application and patient involvement in treatment.

Targeting keratinocytes in the skin with these creams can provide effective and safe pain relief, suggesting that topical formulations may be a promising new approach for managing neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics. Keppel Hesselink, JM., Kopsky, DJ., Bhaskar, AK.[2021]

In a study involving 87 healthy volunteers, providing individuals with control over when they administer a placebo treatment significantly enhanced the effectiveness and duration of placebo analgesia compared to standard passive conditioning.

Participants with instrumental control not only experienced greater pain relief but also showed reduced anxiety responses, suggesting that giving patients control could be a simple and ethical way to improve pain management outcomes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Instrumental Control Enhances Placebo Analgesia. Tang, B., Geers, A., Barnes, K., et al.[2020]

A survey of 11 U.S. physicians revealed that topical compounded pain creams are commonly used for treating musculoskeletal and neuropathic pain, and most prescribers believe these creams are more effective than FDA-approved alternatives.

The majority of physicians reported that using these compounded creams allowed them to reduce narcotic prescriptions, and they considered these compounds to be safe for their patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A brief survey on prescriber beliefs regarding compounded topical pain medications. Warner, M., Tuder, D.[2015]

Citations