Clinical Trial: Harnessing Placebo Effects in Methadone Treatment

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

Brief Summary: This study evaluates the addition of placebo to the normal treatment course of methadone in patients who are undergoing treatment for opioid use disorder. All participants will be enrolled in a methadone outpatient treatment program who have been prescribed a daily regimen of methadone. Half of the participants will be given a placebo pill (to be taken with the methadone), and the other half will be given standard treatment of care.

Detailed Summary: The purpose of this study is to evaluate the effectiveness of pharmacological conditioning via placebo on treatment outcomes in patients newly admitted for methadone maintenance treatment. 120 new patients entering into the Maryland Methadone Treatment Program Center will be recruited to participate in the research study, and in a randomized, controlled trial, will be assigned to groups receiving placebo (Placebo Dose Extension [PDE] group) or Treatment-As-Usual (TAU; Control group). Participants will be told that the study is designed to investigate the efficacy of methadone treatment that is enhanced via inner healing processes (pharmacological conditioning). Participants assigned to the PDE group will be given placebo pills, and will be asked to take one placebo pill for two weeks, immediately prior to receiving their methadone dose, starting on the first day of their methadone treatment (Day 0). On weeks three and four, participants will be instructed to supplement this morning placebo pill dose with a second placebo pill (evening dose), taken twelve hours later at home. The reason for this two-phase placebo pill administration protocol is that a strong association is made between the placebo pill and the methadone in weeks one and two; this strong association continues to be reinforced in weeks 3 and 4. We expect that methadone will act as an unconditioned stimulus and the placebo pill will act as a conditioned stimulus, thus evoking the conditioned responses to methadone of decreased craving and withdrawal. Participants in the Control group will receive the same amount of interaction with the investigators, and like the participants selected to receive placebo, they will be informed of the placebo effect.
Sponsor: University of Maryland

Current Primary Outcome: Dose of methadone [ Time Frame: 28 days ]

The Maryland Methadone Maintenance Treatment Program Center (MMTPC) adheres strictly to SAMHSA standards for medication-assisted treatment of opioid use disorder. Patients entering into the clinic are given an initial evaluation that results in the prescription of a starting and maintenance dose of methadone. Typically, this starting dose is usually around 25-30 mg/d, and increases by 5 mg/every other day to arrive at a maintenance dose within a two-week period (typically, around 60 mg/d). At three weeks, a dose evaluation is given, and the results of this evaluation will confer a recommendation to either maintain, or increase, the maintenance dose. In the MMTPC, approximately 75% of new patients who enter for methadone treatment are given a recommendation to titrate up to a higher dose. The investigators will be documenting the starting, maintenance, as well as the ultimate holding dose that follows the 3-week evaluation.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Adapted Credibility/Expectancy Questionnaire [ Time Frame: Days 14 and 28 ]
    (Only for participants assigned to the Placebo Dose-Extension Group) Expectancy will be assessed using a scale asking participants to rate their answers to 3 questions that assess how much they believe that the Placebo Dose-Extension therapy that they are receiving will help the symptoms that they most want to see improve, as originally implemented by Devilly, G. J. and T. D. Borkovec (2000) "Psychometric properties of the credibility/expectancy questionnaire." J Behav Ther Exp Psychiatry 31(2): 73-86.
  • Urine Drug Testing [ Time Frame: Day 1 and 28 ]
    Urine samples will be collected by project staff and tested by dip test and by a certified laboratory by EMIT for opiates, methadone, buprenorphine, cocaine, benzodiazepines, and marijuana. These results will be used for research purposes only and will not be shared with clinic staff. (This constitutes part of the normal pipeline of intake procedures, but will be repeated at the final assessment time point.)
  • The Subjective Opiate Withdrawal Scale [ Time Frame: Days 14 and 28 ]
    (SOWS; Handlesman et al., 1987): a 16-item patient self-report instrument to assess common subjective symptoms of craving and withdrawal. (This constitutes part of the normal pipeline of intake procedures, but will be repeated for the 14- and 28-day assessments).
  • Days in treatment [ Time Frame: Day 28 ]
    This measure will be used as a compliance assessment, with total number of days in treatment counted, discounting days or appointments that were missed.
  • The Objective Opioid Withdrawal Scale [ Time Frame: Days 1, 14 and 28 ]
    (OOWS; Handelsman et al., 1987), a 13-item clinical assessment of physiological signs of withdrawal.
  • Craving Assessment [ Time Frame: Days 1, 14 and 28 ]
    Participants will rate their craving for drugs using a one-item craving visual-analog scale adapted from MacKillop and Lisman (2008) and Jobes et al (2015), using the wording: "Please rate how intensely you want to use drugs right now; 0 = 'I don't want to use drugs at all,' and 100 = 'I really want to use drugs.'" The single-item VAS generates especially robust and reliable results, perhaps on account of its minimal response burden (Jobes et al., 2015) and minimization of test-retest effects.
  • World Health Organization Quality of Life Scale - Brief (WHOQOL-BREF) [ Time Frame: Days 1, 14 and 28 ]
    The WHOQOL-BREF comprises 26 items, which measure the following broad domains: physical health, psychological health, social relationships, and environment. The WHOQOL-BREF is a shorter version of the original instrument and is better suited for use in large research studies or clinical trials, and has been used previously in the opioid use disorder context and particularly, in this clinic (Mitchell et al., 2015).
  • Compliance [ Time Frame: Days 14 and 28 ]
    (Only for participants assigned to the Placebo Dose-Extension Group) At the 14 and 28-day time point assessments, compliance will be assessed using a VAS asking patients to rate how faithful they were in taking the placebo pill, from 0-100 (0=not faithful at all, 100=completely faithful and took the pill daily at the specified time).
  • Past Week Substance Use [ Time Frame: Days 1, 14 and 28 ]
    Recent drug use in the past week will be assessed using a section of the intake screening assessment that asks the following question: "How many times in the past 2 weeks have used: Heroin/Opiates; Cocaine/crack; Benzos; Alcohol," as well as the frequency of use for each substance: "1-2 times a day or 3+ times a day."
  • Methadone Symptom Severity Checklist [ Time Frame: Days 1, 14 and 28 ]
    (Longwell, Kestler and Cox, 1979). This assessment is designed to have participants rate from 1-5 (with a rating of 5 being most serious) the severity of 38 symptoms of commonly-reported side effects stemming from the use of methadone.
  • Cleveland Clinic Constipation Scoring System [ Time Frame: Days 1, 14 and 28 ]
    (Agachan et al., 1996). This constipation scoring system has 8 questions that allow patients to subjectively report the severity of their symptoms of constipation, a side effect of methadone that is most frequently reported, and which causes much discomfort.


Original Secondary Outcome: Same as current

Information By: University of Maryland

Dates:
Date Received: October 19, 2016
Date Started: January 2017
Date Completion: September 2018
Last Updated: October 20, 2016
Last Verified: October 2016