Open-Label Placebos for Chronic Pain

(HOPE Trial)

Overseen By Study Coordination

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Rhode Island Hospital

Disqualifiers: Cancer, Over 89, Allergy, Worker's comp

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

340 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different explanations (rationales) influence the effectiveness of open-label placebos in reducing chronic low back pain and potentially decreasing prescription opioid use. Open-label placebos are pills that patients know lack active medication, yet they may still provide relief. Participants will be divided into groups, each receiving a placebo with a specific explanation or no treatment, to determine which rationale is most effective. Ideal participants have experienced chronic low back pain for at least three months, with significant daily discomfort. As an unphased trial, this study presents a unique opportunity to contribute to innovative research that could lead to new pain management strategies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

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

Research shows that open-label placebos are generally safe for people. These are pills given to patients who know they contain no real medicine. Studies have found that these placebos can be used without causing harm. For example, in a study on chronic low back pain, participants reported less pain after using open-label placebos, suggesting they are safe for long-term use.

In another study, participants took open-label placebos for three months without any serious side effects. Although these placebos didn't greatly reduce headaches, they remained safe. A review of several studies supports these findings, showing that open-label placebos can improve physical function and pain without causing new health problems.

Overall, while open-label placebos lack active ingredients, research suggests they can be used safely, especially for conditions like chronic pain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exploring open-label placebos (OLPs) for chronic pain because these treatments could potentially offer relief without the active ingredients typically found in pain medications, like NSAIDs or opioids. Unlike standard treatments that rely on chemical compounds to alleviate pain, OLPs involve giving patients placebos with full transparency that they contain no active medication. The unique feature of OLPs is their reliance on the psychological and physiological benefits of believing in treatments, potentially reducing side effects and dependency risks associated with traditional painkillers. By testing different rationales, including mindfulness and standard placebo explanations, researchers aim to uncover how expectation and awareness influence pain management, potentially opening new, safer avenues for chronic pain relief.

What evidence suggests that open-label placebos could be effective for chronic pain?

Research has shown that open-label placebos (OLPs) can help reduce chronic low back pain. In one study, participants taking an OLP reported a pain decrease of 1.49 points on a 0 to 10 scale, while those receiving standard treatment experienced only a 0.24-point reduction. Another study found that OLPs can lower pain by about 0.7 points on the same scale. These findings suggest that even when participants know they are taking a placebo, they can still experience relief. Some studies have also noted improvements in mood and sleep for those with chronic back pain. This evidence supports the idea that OLPs might help manage chronic pain. Participants in this trial will be assigned to different groups; some will receive an open-label placebo along with various informational rationales, while others will receive no treatment but will be provided with basic epidemiological information on chronic pain. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-89 with chronic lower back pain lasting at least 3 months, rating their pain intensity at 4/10 or higher and interference with daily activities at 3/10 or more. Participants must speak English and have access to a smartphone or computer with video capability. Those with cancer-related pain, allergies to placebo ingredients, or receiving worker's compensation are excluded.

Inclusion Criteria

English speaking

Having a smartphone or computer with video access

I have had chronic pain for at least 3 months, with a pain level of 4 or higher.

Exclusion Criteria

Suspected allergy to any placebo ingredient

Currently receiving worker's compensation

I am over 89 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label placebos with different rationales or no treatment for comparison

6 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Open-label Placebo

Trial Overview The study investigates how different explanations given when taking an open-label placebo affect its efficacy on chronic low back pain and prescription opioid use. It compares the effects of various rationales against both a no-treatment group and a group taking placebos without any rationale provided.

How Is the Trial Designed?

Group I: OLP + Standard Rationale Experimental Treatment 2 Interventions

Participants in this group will receive an open-label placebo along with information based on the standard rationales used in other OLP studies.

Group II: OLP + Mindfulness Rationale Experimental Treatment 2 Interventions

Participants in this group will receive an open-label placebo along with information with mindfulness information.

Group III: No Treatment + Control Rationale Placebo Group 1 Intervention

Participants in this group will receive no treatment. They will receive basic epidemiological information on chronic pain to guarantee structural equivalence of the trial design.

Group IV: OLP + Control Rationale Placebo Group 2 Interventions

Participants in this group will receive an open-label placebo along with no information on the placebo effect.. They will receive basic epidemiological information on chronic pain to guarantee structural equivalence of the trial design.

Who Is Running the Clinical Trial?

Rhode Island Hospital

Lead Sponsor

Trials

275

Recruited

71,400+

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]

The placebo effect can significantly relieve pain and improve affective disorders, indicating that inert medications can have real therapeutic benefits for patients.

Despite its potential, the placebo effect is often underutilized in clinical practice and inadequately assessed in clinical trials, highlighting the need for greater recognition and understanding of its mechanisms and impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A guide to the pharmacology of placebos. Gowdey, CW.[2022]

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]

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]

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]

Placebo treatments can be effective in managing chronic pain, and their efficacy is influenced by factors such as the patient-physician relationship rather than just the method of administration (e.g., double blind or open label).

Emerging models like 'predictive coding' and 'bayesian brain' suggest that the brain's expectations and learned experiences play a crucial role in how placebos work, indicating that both chronic pain and its relief through placebos are largely influenced by non-conscious processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. Kaptchuk, TJ., Hemond, CC., Miller, FG.[2022]

Citations

1. nature.com nature.com/articles/s41598-025-09415-y

A systematic review and meta analysis of open label ... This study aimed to analyze the effects of Open-Label Placebo (OLP) on physical function and pain in individuals with chronic musculoskeletal pain.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5113234/

Open-label placebo treatment in chronic low back pain In this study, OLP enhanced pain reduction by 1.49 points on a 0 to 10 scale compared to a 0.24 point change with continued standard treatment without the added ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2823541

Open-Label Placebo Injection for Chronic Back Pain With ... An open-label subcutaneous placebo (saline) injection led to significant improvements in pain intensity, mood, and sleep at 1 month posttreatment compared with ...

4. tandfonline.com tandfonline.com/doi/abs/10.1080/17581869.2025.2467025

Open label placebo for chronic low back pain: a systematic ... Therapeutic effectiveness: Open-label placebo (OLP) has been shown to reduce chronic low back pain (CLBP) by nearly 0.7 points on the 0–10 Numerical Rating ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06931158

Evaluating Open-Label Placebos for Chronic Pain Researchers will compare different rationales given when taking an open-label placebo and a no-treatment group and a no rationale group taking OLPs. Official ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2839764

Open-Label Placebos as Adjunct for the Preventive ... Findings In this randomized clinical trial, a 3-month OLP regimen did not reduce monthly headache days (the primary outcome) or migraine days (a ...

7. programinplacebostudies.org programinplacebostudies.org/wp-content/uploads/2021/10/Carvalho-5-year-follow-up-2021.pdf

Open-label placebo for chronic low back pain: a 5-year ... We found significant reductions in both pain and disability between the baseline assessment immediately before the 3 weeks trial with placebo pills and the ...