Conditioned Open-label Placebos to Facilitate Opioid Reduction in Patients With Subacute or Chronic Pain Pain: a Randomized Controlled Trial (ROM)

Cosima Locher

Status: Enrolling

Conditions: Chronic Pain; Subacute Pain

Treatments: Other: P-Dragees blue Lichtenstein, Placebo dragees; Other: Control group (EM)

Study type: Interventional

Funder types: Other

Identifiers

NCT06350786

ROM Study

PZ00P1_201972 (Other Grant/Funding Number)

Details and patient eligibility

About

This study aims to evaluate whether the reduction of the daily morphine equivalent dose (MED) in patients with subacute and chronic pain 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.

Full description

Pain is a major global health problem and is often treated with opioid medication, although risks outweigh the benefits (EFIC, 2022; Goldberg & McGee, 2011; Sandhu et al., 2018). The administration of an open-label placebo (OLP) treatment, i.e., the placebo treatment with full disclosure of being a placebo, has proven to be an effective treatment in pain syndromes [i.e., chronic low back pain (Carvalho et al., 2016; Kleine-Borgmann et al., 2019) and irritable bowel syndrome (Kaptchuk et al., 2010)]. Likewise, meta-analyses reveal that patients in an OLP condition exhibit significantly greater improvement in pain relief than those in a control group (Buergler et al., 2023; von Wernsdorff et al., 2021). Moreover, and of relevance when it comes to the need to reduce opioid medication, OLPs have been shown to be a promising candidate for drug tapering: 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 (Benedetti, 2008; Doering & Rief, 2012; Martin-Pichora et al., 2011; Price et al., 1999).

A new line of research that indicates that OLPs are effective as an adjunctive treatment for the reduction of drugs have been shown to be feasible for the reduction of active medication in opioid use disorder (Belcher et al., 2019, 2023), acute pain (Bernstein et al., 2019; Flowers et al., 2021; Morales-Quezada et al., 2020; Sezer et al., 2021), chronic posttraumatic pain (Estudillo-Guerra et al., 2021), and ADHD (Sandler et al., 2010; Sandler & Bodfish, 2008).

Despite these promising findings, there is a lack of trials that examine OLP as adjunctive treatment for the reduction of opioid medication in the subacute and chronic pain population. OLPs are suitable for the controlled reduction of long-acting opioids that are embedded in the planned reduction regimen, and could provide a means of harnessing analgesic placebo effects in patients with subacute and chronic pain, without any loss in pain management efficacy. The major goal of our study is therefore to support participants in their aim to reduce their opioid intake.

Enrollment: 86 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed Informed Consent
• ≥ 18 years of age
• German speaking
• Pain lasting ≥ 4 weeks, including subacute pain (4-12 weeks) and chronic pain (>12 weeks)
• Opioid medication for pain management for ≥ 4 weeks
• 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 that is expected to affect opioid intake
• 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 pain specific interventions

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

86 participants in 2 patient groups

Open-Label Placebo

Experimental group

Description:

The intervention involves administering "P-Dragees blue Lichtenstein," blue placebo pills devoid of active ingredients. Each pill contains lactose monohydrate; magnesium stearate; microcrystalline cellulose; sucrose; glucose syrup; corn-starch; highly dispersed silicon dioxide; white clay; macrogol glycerol hydroxy stearate; Gum arabic; montanglycol wax; povidone; talcum; titanium dioxide; calcium carbonate; macrogol 6000; patent blue V; aluminium salt. Participants receive an evidence-based rationale, explaining why the placebo treatment is deemed effective for pain. They are informed that the pills are placebos and are instructed to pair them with opioid medication for 7 days. After 7 days until the end of the study they are instructed to continue to pair their opioid medication with an OLP pill and take additionally placebo pills on the basis of their need. During the intervention, participants use electronic monitoring (EM) to track medication and OLP intakes.

Treatment:

Other: P-Dragees blue Lichtenstein, Placebo dragees

Electronic monitoring (EM) control group

Other group

Description:

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.

Treatment:

Other: Control group (EM)