Harnessing Placebo Effects in Methadone Treatment

August 7, 2020 updated by: Annabelle Belcher, University of Maryland, Baltimore

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

133

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Maryland Methadone Treatment Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Open-Label Placebo (OLP)
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)
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.
No Intervention: Treatment as Usual (TAU)
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?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Three-month dose of methadone
Time Frame: Three months (90 days)
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
Time Frame: 90 and 180 days post-baseline (entry into treatment)
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
Time Frame: One year post-baseline (entry into 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
Time Frame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.
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
Time Frame: Baseline
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
Time Frame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.
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)
Time Frame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.
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)
Time Frame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.
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)
Time Frame: Baseline (entry into treatment), and 1- and 3-months post-baseline
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
Time Frame: Baseline (entry into treatment), and 1- and 3-months post-baseline
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain Catastrophising Scale (PCS)
Time Frame: Baseline (entry into treatment), and 1- and 3-months post-baseline
The PCS is a self-report measure, consisting of 13 items scored from 0 to 4, resulting in a total possible score of 0-52. The higher the score, the more catastrophizing thoughts are present. A cutoff of more than 30 points is considered to be clinically relevant.
Baseline (entry into treatment), and 1- and 3-months post-baseline
Compliance
Time Frame: Two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
Compliance: a visual-analogue scale rating from 0-100 assessing compliance with instructions to take the placebo pill; higher numbers indicate greater compliance.
Two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
Methadone side effects checklist
Time Frame: Two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
The Methadone Side Effects Checklist (Longwell B, Kestler RJ & Cox TJ, 1979) assesses severity of of 38 commonly reported methadone treatment-associated side effects. 38 symptoms are rated 1-5 (1="no problem at all"; 5="a very bad problem") for a total possible score of 38-190. Higher total scores indicate higher severity of symptoms.
Two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
Cleveland Clinic Constipation Scoring system (CCCS)
Time Frame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
The CCCS (Agachan, Chen, Pfeifer, Reissman, Wexner, 1996) is an 8-item scale of self-reported severity of symptoms of constipation. A total score is derived, with a possible score of 0-32. Higher total scores indicate higher severity of symptoms.
Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
Adapted credibility/expectancy questionnaire
Time Frame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
A single-item visual analog scale (0-100) assessment of participant beliefs that the placebo pill would improve symptoms of addiction. Higher scores indicate greater belief/expectation of a beneficial placebo pill effect.
Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
Monetary Choice Questionnaire (MCQ)
Time Frame: Two-weeks post-baseline, and 2-, and 3-months post-baseline
The MCQ (Kirby & Marakovic, 1996) is a 27-item assessment of delay discounting. For each item, the participant chooses between a smaller, immediate monetary reward and a larger, delayed monetary reward. The protocol is scored by calculating where the respondent's answers place him/her amid reference discounting curves, where placement amid steeper curves indicates higher levels of impulsivity.
Two-weeks post-baseline, and 2-, and 3-months post-baseline
Barratt Impulsivity Scale, version 11 (BIS-11)
Time Frame: Two weeks post-baseline
The BIS-11 (Patton, Stanford, Barratt, 1995) is a 30-item assessment that yields information regarding three facets of trait impulsivity (ie, attentional impulsivity, motor impulsivity and non-planning impulsivity). Participants indicate on a four-point Likert-like scale the extent to which each of 30 items describes their overall behavior. A scoring algorithm (with some items reverse-scored) yields 6 first-order and 3 second-order factors, as well as an overall score (a total possible score of 120). Higher values on each of the factors indicate higher levels of impulsivity.
Two weeks post-baseline
Exit survey
Time Frame: Three months post-baseline
A 7-item quantitative and qualitative assessment of how the placebo pill was experienced by participants and their thoughts about their experience participating in the study.
Three months post-baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Collaborators

University of Maryland, College Park

Investigators

  • Principal Investigator: Annabelle M Belcher, PhD, University of Maryland, Baltimore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 5, 2017

Primary Completion (Actual)

July 31, 2020

Study Completion (Actual)

July 31, 2020

Study Registration Dates

First Submitted

October 19, 2016

First Submitted That Met QC Criteria

October 20, 2016

First Posted (Estimate)

October 21, 2016

Study Record Updates

Last Update Posted (Actual)

August 11, 2020

Last Update Submitted That Met QC Criteria

August 7, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00070829

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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