Open-Label Placebo for Chronic Pain

Overseen By Yang Wang, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Maryland, Baltimore

Disqualifiers: Neuromuscular, Cardiovascular, Neurological, Psychiatric, others

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

Compensation: Varies

Number of Visits: 2

111 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if open-label placebo (OLP) pills can improve pain and sleep in individuals with chronic pain from temporomandibular disorders (TMD). It examines whether understanding placebo effects before taking them influences outcomes. Participants will be divided into three groups: one taking OLP with an expectation session, one taking OLP without the session, and one continuing their usual care. Individuals with TMD for over three months who speak English and use a smartphone may be suitable for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative approaches to managing chronic pain.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It seems likely that you can continue your usual care, especially if you are in the standard of care group.

What prior data suggests that open-label placebo is safe for people with temporomandibular disorders?

Research has shown that open-label placebo (OLP) treatments are generally safe. In studies with patients experiencing long-term pain, OLP did not cause significant side effects. For instance, one study on chronic low back pain found that OLP can be safely added to treatment, with only a few participants choosing not to continue after starting. Another study found that OLP injections improved pain, mood, and sleep without major safety issues. Overall, these findings suggest that OLP is well-tolerated and does not pose significant risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using open-label placebos for chronic pain because they challenge traditional ideas about how placebos work. Unlike standard treatments that rely on active medications or therapies, open-label placebos are pills given with full transparency—they contain no active ingredients, and participants know this. The excitement stems from the possibility that simply taking a placebo, even knowing it's a placebo, might still trigger the brain's natural pain-relief mechanisms. This approach could offer a side-effect-free alternative to current pain management strategies, such as opioids or non-steroidal anti-inflammatory drugs (NSAIDs), which often come with significant risks. Additionally, by incorporating expectation management, researchers hope to enhance the placebo effect, potentially leading to even better outcomes for pain relief.

What evidence suggests that this trial's treatments could be effective for chronic pain and sleep quality in TMD?

Research has shown that open-label placebo (OLP) can reduce chronic pain, even when people know they're taking a placebo. For example, a study on chronic low back pain found that patients experienced less pain after taking OLP. Another review found that OLP could improve physical function and reduce pain in individuals with long-term muscle and joint pain. Additionally, OLP injections significantly improved pain, mood, and sleep for those with chronic back pain. In this trial, participants will be assigned to different arms to explore the effects of OLP on chronic pain. These studies suggest that OLP might help with chronic pain, such as jaw disorders, by harnessing the mind's power to influence how the body perceives pain. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-88 with chronic headaches lasting over 3 months, who can communicate via smartphone/text and speak English. They should have a minimum pain level on the Grade Chronic Pain Scale.

Inclusion Criteria

I can speak and write in English.

I have had chronic headaches for at least 3 months.

I have a smartphone and can send text messages.

Timeline for a Trial Participant

Phenotyping

Participants undergo a 2-day phenotyping phase to assess baseline chronic pain and sleep patterns

2 days

1 visit (in-person), 2 days (at-home monitoring)

Intervention

Participants are randomized into groups and undergo a 45-day intervention with open-label placebo and/or expectation management

45 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Open-label placebo

Trial Overview

The study tests if open-label placebo pills, especially when combined with expectation management sessions, can improve pain and sleep in people with temporomandibular disorders. Participants are divided into three groups: one receiving placebo plus expectation talks, another just the placebo, and a third continuing usual care without placebos.

How Is the Trial Designed?

Group I: Open label placebo only arm Experimental Treatment 1 Intervention

Participants who are assigned to the OLP group will be given a bottle of OLP pills. They will be asked to take one pill per day for 45 days. They will be introduced to placebo effects and the therapeutic potential of using open-label placebo for chronic pain management and sleep improvement.

Group II: Open label placebo + expectation management Experimental Treatment 1 Intervention

Participants assigned to this arm will complete an 1 hour discussion about their expectations towards open-label placebo intervention. After that, they will continue with the 2-day run-in period and 45-day intervention. They will be asked to take 1 open-label placebo pill per day, for a total of 45 days.

Group III: Wait-list arm Active Control 1 Intervention

Participants in the wait-list group will not receive OLP pills until the end of the 45-day monitoring period. Therefore, the 45 days without OLP will serve as an no intervention comparators relative to the OLP group.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

This ongoing randomized controlled trial involves 70 patients recovering from dorsal lumbar interbody fusion surgery, investigating the effectiveness of adding open-label placebos to standard opioid treatment to reduce opioid consumption and side effects.

The study aims to provide insights into how open-label placebos can enhance pain management without compromising efficacy, potentially offering a cost-effective strategy to minimize opioid use in acute postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial. Sezer, D., de Leeuw, M., Netzer, C., et al.[2021]

In a review of 18 studies involving 3546 patients with fibromyalgia syndrome, a significant 18.6% of participants experienced a 50% reduction in pain from placebo treatments, highlighting the strong placebo effect in chronic pain trials.

The study also found that 10.9% of patients in placebo groups dropped out due to adverse events, indicating a notable nocebo effect, which suggests that both placebo and nocebo responses play a critical role in the perceived efficacy and safety of drug treatments for fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis. Häuser, W., Sarzi-Puttini, P., Tölle, TR., et al.[2022]

In a review of 42 trials on neuropathic pain and 29 trials on low back pain, it was found that participants on placebo consumed significantly more rescue medication (RM) than those on active drugs, which could mask the true effectiveness of the treatments.

Specifically, in trials showing a small to medium effect size for the investigational drugs, placebo participants used 17% to 30% more RM, highlighting the need for better analytical methods to account for RM consumption in chronic pain studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of rescue medication in placebo-controlled trials of pharmacotherapy for neuropathic pain and low back pain. Grøvle, L., Hasvik, E., Haugen, AJ.[2023]

A 5-year follow-up of patients who participated in a 3-week open-label placebo trial for chronic low back pain showed significant long-term reductions in pain and disability, with improvements persisting over time.

Participants also reported a substantial decrease in the use of pain medications, suggesting that the benefits of open-label placebo treatment may lead to lasting changes in pain management behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label placebo for chronic low back pain: a 5-year follow-up. Carvalho, C., Pais, M., Cunha, L., et al.[2023]

In a study involving knee osteoarthritis and non-radicular low back pain patients, significant placebo effects were observed, particularly in pain intensity and range of motion, indicating that the placebo response can influence both self-reported and performance-based outcomes.

The study found that gender and diagnosis affected the magnitude of placebo responses, with women in the knee osteoarthritis group showing notable improvements, suggesting that these factors should be considered in future clinical trials to better understand and potentially mitigate placebo effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Managing" the Placebo Effect: The Single-Blind Placebo Lead-in Response in Two Pain Models. Harden, RN., Saracoglu, M., Connolly, S., et al.[2018]

In a study involving 52 Japanese patients with chronic low back pain, the addition of open-label placebo (OLP) to standard treatment did not show superior benefits compared to standard treatment alone after 3 and 12 weeks.

Both groups experienced significant improvements in functional disability, indicating that while OLP did not enhance outcomes, standard treatment was effective in reducing disability in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Placebo Trial among Japanese Patients with Chronic Low Back Pain. Ikemoto, T., Ueno, T., Arai, YC., et al.[2021]

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The study suggests that honestly described open-label placebo pills may have a role in chronic low back pain relief.

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This study aimed to analyze the effects of Open-Label Placebo (OLP) on physical function and pain in individuals with chronic musculoskeletal pain.

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An open-label subcutaneous placebo (saline) injection led to significant improvements in pain intensity, mood, and sleep at 1 month posttreatment compared with ...

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Placebo Comparator : OLP + Control Rationale. Participants in this group will receive an open-label placebo along with no information on the placebo effect..

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Currently published open-label placebo studies are small, ranging from 15 to 83 patients, and although a no-intervention arm is included, they often lack the ...

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No long-term effects after a 3-week open-label placebo...

Given OLP's tolerability and safety, these findings indicate that they can have clinically relevant short-term benefits. Because most trials used a 2- to 3-week ...