Clinical trial NCT02941809: Harnessing Placebo Effects in Methadone Treatment
Official title: Open-labeled Dose-extending Placebos as an Adjunct to Methadone Treatment: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Opioid-use Disorder
Opioid-Related Disorders
Keywords: medications for opioid use disorder
methadone
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: University of Maryland, College Park
First posted: 2016-10-21
Enrollment: 133
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: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Three-month dose of methadone
timeFrame: Three months (90 days)
Secondary outcomes:
measure: Treatment Retention
timeFrame: 90 and 180 days post-baseline (entry into treatment)
measure: Total number of days retained in treatment
timeFrame: One year post-baseline (entry into treatment)
measure: Mean number of days of self-reported drug use
timeFrame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.
measure: Urine Testing- Quick-tox Screen
timeFrame: Baseline
measure: Craving assessment
timeFrame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.
measure: Objective Opioid Withdrawal Scale (OOWS)
timeFrame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.
measure: Subjective Opioid Withdrawal Scale (SOWS)
timeFrame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline.
measure: Pittsburgh Sleep Quality Inventory (PSQI)
timeFrame: Baseline (entry into treatment), and 1- and 3-months post-baseline
measure: World Health Organization Quality of Life - Brief (WHOQOL-BREF) Assessment
timeFrame: Baseline (entry into treatment), and 1- and 3-months post-baseline
Other outcomes:
measure: Pain Catastrophising Scale (PCS)
timeFrame: Baseline (entry into treatment), and 1- and 3-months post-baseline
measure: Compliance
timeFrame: Two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
measure: Methadone side effects checklist
timeFrame: Two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
measure: Cleveland Clinic Constipation Scoring system (CCCS)
timeFrame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
measure: Adapted credibility/expectancy questionnaire
timeFrame: Baseline (entry into treatment), two-weeks post-baseline, and 1-, 2-, and 3-months post-baseline
measure: Monetary Choice Questionnaire (MCQ)
timeFrame: Two-weeks post-baseline, and 2-, and 3-months post-baseline
measure: Barratt Impulsivity Scale, version 11 (BIS-11)
timeFrame: Two weeks post-baseline
measure: Exit survey
timeFrame: Three months post-baseline
Locations:
city: Baltimore
country: United States
facility: Maryland Methadone Treatment Center
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Annabelle M Belcher, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Belcher AM, Cole TO, Greenblatt AD, Hoag SW, Epstein DH, Wagner M, Billing AS, Massey E, Hamilton KR, Kozak ZK, Welsh CJ, Weintraub E, Wickwire EM, Wish ED, Kaptchuk TJ, Colloca L. Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment. BMJ Open. 2019 Jun 21;9(6):e026604. doi: 10.1136/bmjopen-2018-026604.
citation: Cai NS, Quiroz C, Bonaventura J, Bonifazi A, Cole TO, Purks J, Billing AS, Massey E, Wagner M, Wish ED, Guitart X, Rea W, Lam S, Moreno E, Casado-Anguera V, Greenblatt AD, Jacobson AE, Rice KC, Casado V, Newman AH, Winkelman JW, Michaelides M, Weintraub E, Volkow ND, Belcher AM, Ferre S. Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids. J Clin Invest. 2019 Mar 26;129(7):2730-2744. doi: 10.1172/JCI126912.