Conditioned Open-label Placebos to Facilitate Opioid Reduction in Patients With Chronic Non-cancer Pain
- Conditions
- Chronic Non-cancer Pain
- Interventions
- Other: P-Dragees blue Lichtenstein, Placebo drageesOther: Control group (EM)
- Registration Number
- NCT06350786
- Lead Sponsor
- Cosima Locher
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 86
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open-Label Placebo P-Dragees blue Lichtenstein, Placebo dragees 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. Electronic monitoring (EM) control group Control group (EM) 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.
- Primary Outcome Measures
Name Time Method Daily opioid consumption (MED): 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. Cumulative dose (i.e. total amount) of opioid pain medication consumption based on daily morphine equivalent doses (MED). Data is collected in SEMA3 app.
- Secondary Outcome Measures
Name Time Method Subjective opioid withdrawal symptoms 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. Subjective opioid withdrawal will be assessed with the Subjective Opiate Withdrawal Scale (SOWS). The intensity of the withdrawal symptoms is rated by the patient on a scale between 0 (= not at all) and 4 (= extremely), the scores for individual symptoms are added to a total sum score, which can range from 0 to 64. The secondary endpoint will be the subjective opioid withdrawal score at study end (t3).
Pain severity 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. Pain severity is assessed using the ICD-11 specifiers or 'extension codes'. The index combines patient-assessed ratings of pain intensity, pain-related distress and pain-related interference. Each of these ratings is assessed on an 11-point NRS rating scale, and these are mapped into the following categories depending on the NRS score: none = NRS 0, mild = NRS 1 - 3, moderate = NRS 4 - 6 and severe = NRS 7 - 10.
Pain disability 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. Pain disability is assessed using the pain disability index (PDI) to determine the subjective degree of self-reported impairment caused by the pain problem in everyday life. Seven domains of life are assessed: (1) family and domestic responsibilities, (2) recreation, (3) social activities, (4) occupation, (5) sexual life, (6) self-care and (7) essential activities. The scale ranges from 0 "no impairment" (minimum) - 10 "full impairment" (maximum).
Anxiety 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. Anxiety is assessed using the German version of the GAD-7. It is a brief instrument for assessing self-reported generalized anxiety disorder (GAD) symptoms with seven items asking about the main diagnostic criteria of GAD according to the DSM-IV and the ICD-10 criteria. The questions refer to the past two weeks. The scale ranges from "not at all" (minimum); "On some days"; "On more than half of the days"; "almost every day" (maximum).
Depression 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. Depression is assessed using Patient Health Questionnaire (PHQ-D) consisting of nine items referring to the past two weeks. The German version of the PHQ was derived from the 'Prime MD Patient Health Questionnaire' and is based on the criteria of the DSM-IV. The scale ranges from "not at all" (minimum); "On some days"; "On more than half of the days"; "almost every day" (maximum).
Pain Opioid Analgesics Beliefs Scale - Cancer 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. The POABS-CA in the German version measures pain opioid beliefs based on two components with 10 items and a 5-point Likert scale ranging from 0 ("strongly disagree") to 4 ("strongly agree"). The higher the score, the more negative was the opinion about the use of opioid analgesics for cancer pain, and the stronger was the belief that pain should be endured.
Treatment Expectancy 2 One-time assessment: measured on day 0 at the first intervention visit (baseline). Expectation measures will be measured in analogy to the most relevant outcomes. Second, to measure the expected withdrawal symptoms at the end of the study, items from the SOWS questionnaire will be used, which are expanded with instructions regarding the expectation.
Treatment Expectancy 1 One-time assessment: measured on day 0 at the first intervention visit (baseline). Expectation measures will be measured in analogy to the most relevant outcomes. First, subjectively expected amount (dose) of opioid medication taken will be examined. For this, the following item will be used at the end of the study "How much opioid medication do you think you will be taking at the end of the study?" The item is answered by naming the type of medication, frequency and amount (dose) of medication.
Placebo pill count 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. The intake of placebo pills by the OLP-group will be electronically monitored using survey provided by the app SEMA3. For statistical analysis a ratio will be calculated. A value of the ration close to 1 indicated a more accurate data entry of the placebo pill intake.
Opioid adherence 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. Opioid adherence trajectories will be measured with the app SEMA3 in both groups. In the EM control group, a print of the actual data report from the app (i.e. graph reflecting the pattern of opioid medication intake) will be the basis for the EM-Feedback.
Trial Locations
- Locations (1)
University Hospital Zurich, Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine
🇨🇭Zurich, Switzerland