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?

The goal of this clinical trial is to examine the effect of rationale condition when taking open-label placebos on pain by 1) comparing each rationale to the no rationale control condition and the no treatment control condition; and 2) comparing the rationale conditions to each other. We also aim to examine the effect of rationale condition on prescription opioid use by 1) comparing each rationale to the no rationale control condition and the no treatment control condition; and 2) comparing the rationale conditions to each other. This study will include patients with chronic low back pain. The main question it aims to answer is: How do rationales influence the effects of open-label placebos? Researchers will compare different rationales given when taking an open-label placebo and a no-treatment group and a no rationale group taking OLPs.

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 open-label placebo treatment safe for humans?

Open-label placebos, where patients know they are taking a placebo, have been studied for various conditions and are generally considered safe, as they do not contain active medication that could cause side effects. ^{1 2 3 4 5}

How does the open-label placebo treatment differ from other treatments for chronic pain?

Open-label placebo treatment is unique because it involves giving patients a placebo (a pill with no active medication) while fully informing them that it is a placebo. Unlike traditional treatments that rely on active ingredients, this approach leverages the psychological effects of taking a pill, which can still lead to pain relief and reduced disability in chronic pain patients. ^{2 3 4 6 7}

What evidence supports the effectiveness of open-label placebo treatment for chronic pain?

Research shows that open-label placebos, where patients know they are taking a placebo, can still help relieve symptoms in conditions like pain, even when patients are aware the pills contain no active medication. This suggests that the act of taking a pill and the supportive relationship with healthcare providers can enhance the placebo effect, providing real symptom relief. ^{2 8 9 10 11}

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

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]

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]

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]

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 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]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

[Appearances are not deceptive: clinical evidence and new research approaches to open-label placebo]. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Can insights from placebo and nocebo mechanisms studies improve the randomized controlled trial? [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of rescue medication in placebo-controlled trials of pharmacotherapy for neuropathic pain and low back pain. [2023]

5. Canada pubmed.ncbi.nlm.nih.gov

A guide to the pharmacology of placebos. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Pain Response to Open Label Placebo in Induced Acute Pain in Healthy Adult Males. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

No long-term effects after a 3-week open-label placebo treatment for chronic low back pain: a 3-year follow-up of a randomized controlled trial. [2023]

9. Italy 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Effects of open-label placebo on pain, functional disability, and spine mobility in patients with chronic back pain: a randomized controlled trial. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Open-Label Placebo Trial among Japanese Patients with Chronic Low Back Pain. [2021]