Conditioned Open-label Placebos to Facilitate Opioid Reduction in Patients With Chronic Non-cancer Pain

NCT ID: NCT06350786

Last Updated: 2025-04-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-12

Study Completion Date

2026-07-31

Brief Summary

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This study aims to evaluate whether the reduction of the daily morphine equivalent dose (MED) in patients with chronic non-cancer pain (CNCP) can be decreased with an open-label placebo (OLP) intervention in comparison to an electronic monitoring (EM) control group. The participants will receive the intervention (OPL or EM) over the duration of six weeks. Diverse psychological and health measures will be assessed with questionnaires over the course of the intervention. Furthermore, evaluation outcomes, qualitative outcomes and safety outcomes will be assessed. It is hypothesized that the OLP-intervention group in comparison to the EM-control group will have a significantly lower consumption of MED over the course of the study. Furthermore, this study aims to evaluate whether the OLP intervention can reduce opioid withdrawal symptoms in comparison to the control group.

Detailed Description

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CNCP is a major global health problem and is often treated with opiod medication, although risks outweigh the benefits. Therefore, recent studies suggest that an open-label placebo (OLP) treatment, the placebo treatment with full disclosure of being a placebo, has proven to be an effective, clinically relevant, and evidence-based treatment in CNCP syndromes. Furthermore, a new line of research indicated that OLPs have been shown to be feasible for the reduction of active medication in opioid use disorder. In line with the conditioning paradigm, the drug as the unconditioned stimulus is paired with the neutral stimulus of an OLP in a learning phase. Then, the OLP alone becomes a conditioned stimulus.

Conditions

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Chronic Non-cancer Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Open-Label Placebo

The intervention involves administering "P-Dragees blue Lichtenstein," blue placebo pills devoid of active ingredients. Each pill contains lactose monohydrate; magnesium stearate (Ph. Eur.); microcrystalline cellulose; sucrose; glucose syrup; corn-starch; highly dispersed silicon dioxide; white clay; macrogol glycerol hydroxy stearate (Ph. Eur.); Gum arabic; montanglycol wax; povidone (K 25); talcum; titanium dioxide (E 171); calcium carbonate; macrogol 6000; patent blue V; aluminium salt (E 131).

Participants will be informed that the pills are placebos and will be instructed to pair them with opioid medication for 7 days. After 7 days until the end of the study they will be instructed to continue to pair their opioid medication with an OLP pill and take additionally placebo pills on the basis of their need.

An evidence-based rationale will be provided, explaining why the placebo treatment is deemed effective for pain. This rationale will precede the OLP intake procedure.

Group Type EXPERIMENTAL

P-Dragees blue Lichtenstein, Placebo dragees

Intervention Type OTHER

In the intervention group, open-label placebos are administered within the framework of a mind-body management intervention approach, which in turn is consistent with the biopsychosocial model of pain and with a patient-centred approach. The verbal interaction follows the four discussion points:

1. Opioids work by telling the body that participants are not experiencing as much pain;
2. Placebos should be taken every time an opioid is taken which supports the reduction of opioid medication (shown by previous studies);
3. By pairing the pills together the brain will learn to release chemicals like endorphins that cause pain-relief in response to the placebo, just as it does in response to the opioid;
4. At a certain point, placebos might provide adequate pain relief, and the participants might need less opioids.

Electronic monitoring (EM) control group

EM is a method to objectively measure adherence and serves as the primary intervention component on the basis of which adherence trajectories will be discussed. The participants in the EM control group will receive an evidence-based rational designed to foster positive expectations and will be instructed on the mechanisms of EM.

The EM control group is structurally equivalent to the OLP group referring to the number and duration of contacts between participants and the study team members as well as to the format of the intervention and the quality of the interaction.

Group Type OTHER

Control group (EM)

Intervention Type OTHER

In the EM control group, the focus lies on the electronic monitoring (EM) of the opioid intake. The treatment rationale is designed to facilitate the reduction of opioid medication by promoting a positive attitude towards the implementation of the reduction. The verbal interaction follows the four discussion points:

1. The collection of EM data allows for greater patients' sense of agency over medication treatment;
2. Tracking of opioid medication use supports the reduction of opioid medication (shown by previous studies);
3. The EM is a useful tool, and daily recording of opioid medication intake should be done;
4. At a certain point, EM might provide adequate pain relief, and participants might need less opioids.

Interventions

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P-Dragees blue Lichtenstein, Placebo dragees

In the intervention group, open-label placebos are administered within the framework of a mind-body management intervention approach, which in turn is consistent with the biopsychosocial model of pain and with a patient-centred approach. The verbal interaction follows the four discussion points:

1. Opioids work by telling the body that participants are not experiencing as much pain;
2. Placebos should be taken every time an opioid is taken which supports the reduction of opioid medication (shown by previous studies);
3. By pairing the pills together the brain will learn to release chemicals like endorphins that cause pain-relief in response to the placebo, just as it does in response to the opioid;
4. At a certain point, placebos might provide adequate pain relief, and the participants might need less opioids.

Intervention Type OTHER

Control group (EM)

In the EM control group, the focus lies on the electronic monitoring (EM) of the opioid intake. The treatment rationale is designed to facilitate the reduction of opioid medication by promoting a positive attitude towards the implementation of the reduction. The verbal interaction follows the four discussion points:

1. The collection of EM data allows for greater patients' sense of agency over medication treatment;
2. Tracking of opioid medication use supports the reduction of opioid medication (shown by previous studies);
3. The EM is a useful tool, and daily recording of opioid medication intake should be done;
4. At a certain point, EM might provide adequate pain relief, and participants might need less opioids.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Signed Informed Consent
* ≥ 18 years of age
* German speaking
* Chronic non-cancer pain ≥ 6 months in duration
* Chronic opioid medication for \> 3 months
* Oral intake of opioid medication
* Motivation for opioid reduction
* Participants have a primary treating physician who performs the reduction of the opioid medication
* Having access to a computer or tablet with an email-account

Exclusion Criteria

* Having psychotic symptoms
* Suicidality
* Cognitive impairment to everyday life
* Planned surgery within the next two months
* Known illegal drug or harmful alcohol consumption
* Intolerance of the ingredients of the placebo pill (e.g., lactose, sucrose, corn-starch)
* Serious health problems that make study participation impossible
* Simultaneous participation in other studies with investigational drugs or CNCP specific interventions
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Brown University

OTHER

Sponsor Role collaborator

University of Basel

OTHER

Sponsor Role collaborator

Cosima Locher

OTHER

Sponsor Role lead

Responsible Party

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Cosima Locher

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Cosima Locher, PhD

Role: PRINCIPAL_INVESTIGATOR

USZ

Locations

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University Hospital Zurich, Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine

Zurich, Canton of Zurich, Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Cosima Locher, PhD

Role: CONTACT

+41 44 255 12 03

Kiara Bodonyi, MSc

Role: CONTACT

+41 44 255 14 24

Facility Contacts

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Cosima Locher, PhD

Role: primary

+41 44 255 12 03

References

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Buergler S, Sezer D, Gaab J, Locher C. The roles of expectation, comparator, administration route, and population in open-label placebo effects: a network meta-analysis. Sci Rep. 2023 Jul 22;13(1):11827. doi: 10.1038/s41598-023-39123-4.

Reference Type BACKGROUND
PMID: 37481686 (View on PubMed)

Belcher AM, Cole TO, Massey E, Billing AS, Wagner M, Wooten W, Epstein DH, Hoag SW, Wickwire EM, Greenblatt AD, Colloca L, Rotrosen J, Magder L, Weintraub E, Wish ED, Kaptchuk TJ. Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237099. doi: 10.1001/jamanetworkopen.2023.7099.

Reference Type BACKGROUND
PMID: 37043203 (View on PubMed)

Bernstein MH, Magill M, Weiss AP, Kaptchuk TJ, Blease C, Kirsch I, Rich JD, Becker SJ, Mach S, Beaudoin FL. Are Conditioned Open Placebos Feasible as an Adjunctive Treatment to Opioids? Results from a Single-Group Dose-Extender Pilot Study with Acute Pain Patients. Psychother Psychosom. 2019;88(6):380-382. doi: 10.1159/000503038. Epub 2019 Sep 27. No abstract available.

Reference Type BACKGROUND
PMID: 31563914 (View on PubMed)

Estudillo-Guerra MA, Mesia-Toledo I, Schneider JC, Morales-Quezada L. The Use of Conditioning Open-Label Placebo in Opioid Dose Reduction: A Case Report and Literature Review. Front Pain Res (Lausanne). 2021 Jul 12;2:697475. doi: 10.3389/fpain.2021.697475. eCollection 2021.

Reference Type BACKGROUND
PMID: 35295534 (View on PubMed)

Flowers KM, Patton ME, Hruschak VJ, Fields KG, Schwartz E, Zeballos J, Kang JD, Edwards RR, Kaptchuk TJ, Schreiber KL. Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial. Pain. 2021 Jun 1;162(6):1828-1839. doi: 10.1097/j.pain.0000000000002185.

Reference Type BACKGROUND
PMID: 33449503 (View on PubMed)

Morales-Quezada L, Mesia-Toledo I, Estudillo-Guerra A, O'Connor KC, Schneider JC, Sohn DJ, Crandell DM, Kaptchuk T, Zafonte R. Conditioning open-label placebo: a pilot pharmacobehavioral approach for opioid dose reduction and pain control. Pain Rep. 2020 Jul 20;5(4):e828. doi: 10.1097/PR9.0000000000000828. eCollection 2020 Jul-Aug.

Reference Type BACKGROUND
PMID: 32766465 (View on PubMed)

Sezer D, de Leeuw M, Netzer C, Dieterle M, Meyer A, Buergler S, Locher C, Ruppen W, Gaab J, Schneider T. Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial. Front Med (Lausanne). 2021 Nov 5;8:687398. doi: 10.3389/fmed.2021.687398. eCollection 2021.

Reference Type BACKGROUND
PMID: 34805194 (View on PubMed)

Carratta K, Bodonyi K, Frey Nascimento A, Friis D, von Kanel R, Bircher L, Koechlin H, Bernstein M, Streitberger K, Arnet I, Roth AJ, Ronel J, Olliges E, Locher C. Conditioned open-label placebos to facilitate opioid reduction in patients with chronic non-cancer pain: study protocol of a randomised controlled trial. BMJ Open. 2025 May 24;15(5):e098253. doi: 10.1136/bmjopen-2024-098253.

Reference Type DERIVED
PMID: 40413049 (View on PubMed)

Other Identifiers

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PZ00P1_201972

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ROM Study

Identifier Type: -

Identifier Source: org_study_id

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