Clinical trial NCT06350786: Conditioned Open-label Placebos to Facilitate Opioid Reduction in Patients With Chronic Non-cancer Pain
Official title: Conditioned Open-label Placebos to Facilitate the Reduction of Opioid Medication (ROM) in Patients With Chronic Non-cancer Pain: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Non-cancer Pain
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Brown University
name: University of Basel
First posted: 2024-04-05
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Daily opioid consumption (MED):
timeFrame: Daily measure: starts on day 1 after the first intervention visit (baseline, day 0) after randomization and ends on day 42 at the end of the study.
Secondary outcomes:
measure: Subjective opioid withdrawal symptoms
timeFrame: Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and on day 42 at the end of the study.
measure: Pain severity
timeFrame: Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.
measure: Pain disability
timeFrame: Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.
measure: Anxiety
timeFrame: Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.
measure: Depression
timeFrame: Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.
measure: Pain Opioid Analgesics Beliefs Scale - Cancer
timeFrame: Measured three times: on day 0 at the first intervention visit (baseline), on day 7, and at the end of the study on day 42.
measure: Treatment Expectancy 1
timeFrame: One-time assessment: measured on day 0 at the first intervention visit (baseline).
measure: Treatment Expectancy 2
timeFrame: One-time assessment: measured on day 0 at the first intervention visit (baseline).
measure: Placebo pill count
timeFrame: Daily measure: starts 1 day after the first intervention visit (baseline, day 0) after randomization and ends on day 42 at the end of the study.
measure: Opioid adherence
timeFrame: Daily measure: starts 1 day after the first intervention visit (baseline, day 0) after randomization and ends on day 42 at the end of the study.
Other outcomes:
measure: Rationale credibility
timeFrame: One-time assessment: measured on day 42 at the end of the study.
measure: Placebo understanding
timeFrame: One-time assessment: measured on day 42 at the end of the study.
measure: Patient Provider Connection
timeFrame: One-time assessment: measured on day 42 at the end of the study.
measure: Medication history
timeFrame: Measured two times: on day 0 at the first intervention visit (baseline) and on day 42 at the end of the study.
measure: Primary treating physicians' acceptability of the OLP approach:
timeFrame: One-time assessment, measured before study start: on day -14, prior to the first intervention visit (baseline, day 0).
measure: Primary treating physicians' treatment expectancies
timeFrame: One-time assessment, measured before study start: on day -14, prior to the first intervention visit (baseline, day 0).
measure: Qualitative Outcomes
timeFrame: One-time assessment: measured at the end of the study on day 42.
measure: Additional Symptoms
timeFrame: Measured two times: on day 7 after the first intervention visit (baseline) and on day 42.
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine
Study officials:
affiliation: USZ
name: Cosima Locher, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.