Harnessing Placebo Effects in Methadone Treatment

Study Overview
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Brief Summary
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More than 2 million individuals in the United States have an Opioid Use Disorder (OUD). Methadone maintenance treatment is the gold standard of medication-assisted treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects. These adverse effects make enhancing the effectiveness of lower doses of methadone an attractive therapeutic goal. Long recognized for its capacity to enhance treatment outcomes for a wide range of neuropsychiatric disorders including pain, the placebo effect offers an as-yet untested avenue to such an enhancement. This approach is particularly compelling given that individuals with substance use disorder tend to have higher salience attribution, and may thereby be more sensitive to placebo effects. Our study combines two promising clinical methodologies-open-label placebo and conditioning-to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients.

Detailed Description
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A total of 120 newly-enrolled treatment-seeking OUD patients will be randomly assigned to one of two different groups: either methadone plus daily open-label placebo (OLP; treatment group), or methadone/Treatment as Usual (TAU; control). Participants will meet with study team members five times over the course of three months of treatment with methadone (baseline, 2 weeks, and 1, 2 and 3 months post-baseline). Throughout this study time period, methadone dosages will be adjusted by an addiction clinician blind to patient assignment, per standard clinical methods. The primary outcome is methadone dose at three months. Secondary outcomes include self-report of drug use; 3-month urine toxicology screen results; and treatment retention. Exploratory outcomes include several environmental as well as personality factors associated with OUD and with propensity to demonstrate a placebo effect.

Official Title
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Open-labeled Dose-extending Placebos as an Adjunct to Methadone Treatment: A Pilot Study

Conditions
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Opioid-use Disorder, Opioid-Related Disorders

Intervention / Treatment
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* Behavioral: Open-Label Placebo (OLP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (age 18 or over) Newly-admitted to the methadone treatment program Exclusion Criteria: Pregnancy Transfers- patients who have initiated methadone treatment course at another methadone treatment facility Hospital transfers- patients who initiated methadone treatment course in a hospital setting Criminal justice referral

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-Label Placebo (OLP)<br>Participants who are randomly assigned to group OLP will receive placebo pills. In Phase 1 of the study (first two weeks), participants in this group are given one pill, to be taken concomitant with the methadone. In Phase 2 (3 weeks up to 3 months), OLP participants continue to take the single (morning, or AM) pill, and are given a second pill in a bottle as a take-home. OLP participants will meet with the study team at five time points: at baseline (entry into treatment), 2 weeks post-baseline, and 1-, 2- and 3-months post-baseline. | Behavioral: Open-Label Placebo (OLP)<br>* We are designating this as a behavioral intervention for two reasons: (1) the placebo pill is physiologically inert and is not classified under FDA regulations; and (2) other studies have demonstrated that the efficacy of the placebo pill is strongly dependent on the participants' anticipation of an effect. We are presenting the pill's efficacy in an open and transparent way to the participants, but using a positive frame. We feel that this qualifies the placebo pill use as a behavioral intervention, in the same general category as exercise or relaxation.<br>|
| No Intervention: Treatment as Usual (TAU)<br>Participants assigned to TAU will not be given placebo pills, but all interactions with the study team (5 meetings total) will be matched in frequency and length. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Three-month dose of methadone | Mean dose of methadone at 3 months (90 days) post-baseline (entry into treatment) will be evaluated for each of the two arms. | Three months (90 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Retention | Three-month (90-day) and 6-month (180 day) treatment retention as a binomial (yes/no) variable outcome | 90 and 180 days post-baseline (entry into treatment) | 
| Total number of days retained in treatment | Total number of days retained in methadone treatment, up to 365 days | One year post-baseline (entry into treatment) | 
| Mean number of days of self-reported drug use | Number of days of self-reported drug use will be obtained at all five study meetings time points (baseline, 2-weeks post-baseline, and 1-, 2-, and 3-months post-baseline) for each of the following substances: opiates, cocaine, benzodiazepines, alcohol, and a single, all-encompassing category of other drug use. | Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline. | 
| Urine Testing- Quick-tox Screen | Urine toxicology screening via a point of care Quik-tox screen- panel of 13 drugs to determine the presence (positive/negative) of Cocaine, Opiates, Methamphetamine, Cannabis, Amphetamines, Phencyclidine, Benzodiazepines, Barbiturates, Methadone, Oxycodone, MDMA, Buprenorphine, and Fentanyl. | Baseline | 
| Craving assessment | An adapted one-item visual-analogue scale to assess drug craving. The scale ranges from 0-100 (0- craving not at all, 50- neutral, 100- Very much). | Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline. | 
| Objective Opioid Withdrawal Scale (OOWS) | A 13-item clinical assessment of physiological signs of withdrawal conducted by the investigator or a research team member. Scores of 0-1 are given for each item and scores are summed ranging from 0-13. | Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline. | 
| Subjective Opioid Withdrawal Scale (SOWS) | A 16-item patient self-report instrument to assess common subjective symptoms of craving and withdrawal. Scores of 0-4 are given for each item and total scores are summed ranging from 0-64. | Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline. | 
| Pittsburgh Sleep Quality Inventory (PSQI) | A 19-item validated tool to assess sleep quality. The 19 self-rated items are combined to form 7 component scores, each of which has a range of 0-3 points. In all cases, a score of 0 indicates no difficulty, while a score of 3 indicates severe difficulty. The 7 component scores are then added to added a global score, with a range of 0-21 points. | Baseline (entry into treatment), and 1- and 3-months post-baseline | 
| World Health Organization Quality of Life - Brief (WHOQOL-BREF) Assessment | The WHOQOL-BREF is a 26-item assessment that produces a quality of life profile with four domain scores and two items that are examined separately. The mean score of items within each domain is used to calculate the domain score, which are then transformed to scale scores. The range of scores is between 15 to 105, with a higher score or number being indicative of a higher quality of life. | Baseline (entry into treatment), and 1- and 3-months post-baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methadone, medications for opioid use disorder