Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment
Introduction More than 2 million individuals in the USA have an opioid use disorder (OUD). Methadone maintenance treatment is the gold standard of medication-based treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects. Th...
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| Format: | Article |
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BMJ Publishing Group
2019-06-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/9/6/e026604.full |
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| author | Annabelle M Belcher Thomas O Cole Aaron D Greenblatt Stephen W Hoag David H Epstein Michael Wagner Amy S Billing Ebonie Massey Kristen R Hamilton Zofia K Kozak Christopher J Welsh Eric Weintraub Emerson M Wickwire Eric D Wish Ted J Kaptchuk Luana Colloca |
| author_facet | Annabelle M Belcher Thomas O Cole Aaron D Greenblatt Stephen W Hoag David H Epstein Michael Wagner Amy S Billing Ebonie Massey Kristen R Hamilton Zofia K Kozak Christopher J Welsh Eric Weintraub Emerson M Wickwire Eric D Wish Ted J Kaptchuk Luana Colloca |
| author_sort | Annabelle M Belcher |
| collection | DOAJ |
| description | Introduction More than 2 million individuals in the USA have an opioid use disorder (OUD). Methadone maintenance treatment is the gold standard of medication-based 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 recognised 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—conditioning/dose-extension and open-label placebo—to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients.Methods and analysis A total of 120 newly enrolled treatment-seeking OUD patients will be randomly assigned to one of two different groups: either methadone plus daily placebo dose-extension (PDE; treatment group) or methadone/treatment as usual (control). Participants will meet with study team members five times over the course of 3 months of treatment with methadone (baseline, 2 weeks, and 1, 2 and 3 months postbaseline). 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 3 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.Ethics and dissemination Human subjects oversight for this study is provided by the University of Maryland, Baltimore and University of Maryland, College Park Institutional Review Boards. Additionally, the study protocol is reviewed annually by an independent Data and Safety Monitoring Board. Study results will be disseminated via research conference presentations and peer-reviewed publications.Trial registration number NCT02941809. |
| format | Article |
| id | doaj-art-ea16ceebd46240af8f0af64c89fceff9 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2019-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-ea16ceebd46240af8f0af64c89fceff92025-02-09T06:35:11ZengBMJ Publishing GroupBMJ Open2044-60552019-06-019610.1136/bmjopen-2018-026604Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatmentAnnabelle M Belcher0Thomas O Cole1Aaron D Greenblatt2Stephen W Hoag3David H Epstein4Michael Wagner5Amy S Billing6Ebonie Massey7Kristen R Hamilton8Zofia K Kozak9Christopher J Welsh10Eric Weintraub11Emerson M Wickwire12Eric D Wish13Ted J Kaptchuk14Luana Colloca151 Department of Psychiatry, Division of Addiction Research and Treatment, University of Maryland School of Medicine, Baltimore, Maryland, USA1 Department of Psychiatry, Division of Addiction Research and Treatment, University of Maryland School of Medicine, Baltimore, Maryland, USA1 Department of Psychiatry, Division of Addiction Research and Treatment, University of Maryland School of Medicine, Baltimore, Maryland, USA2 Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA3 Real-world Assessment, Prediction and Treatment Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USADepartment of Pediatrics and Adolescent Medicine, Division of Neonatology, Intensive Care, and Pediatric Neurology, Medical University Vienna, Vienna, Austria4 University of Maryland Center for Substance Abuse Research, College Park, Maryland, USA4 University of Maryland Center for Substance Abuse Research, College Park, Maryland, USA5 Department of Psychology, University of Maryland, College Park, Maryland, USA6 Medical School Training Program, University of Maryland School of Medicine, Baltimore, Maryland, USA1 Department of Psychiatry, Division of Addiction Research and Treatment, University of Maryland School of Medicine, Baltimore, Maryland, USA1 Department of Psychiatry, Division of Addiction Research and Treatment, University of Maryland School of Medicine, Baltimore, Maryland, USA7 Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA4 University of Maryland Center for Substance Abuse Research, College Park, Maryland, USA9 Program in Placebo Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USADepartment of Pain and Translational Symptom Science, University of Maryland School of Nursing, Baltimore, Maryland, USAIntroduction More than 2 million individuals in the USA have an opioid use disorder (OUD). Methadone maintenance treatment is the gold standard of medication-based 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 recognised 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—conditioning/dose-extension and open-label placebo—to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients.Methods and analysis A total of 120 newly enrolled treatment-seeking OUD patients will be randomly assigned to one of two different groups: either methadone plus daily placebo dose-extension (PDE; treatment group) or methadone/treatment as usual (control). Participants will meet with study team members five times over the course of 3 months of treatment with methadone (baseline, 2 weeks, and 1, 2 and 3 months postbaseline). 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 3 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.Ethics and dissemination Human subjects oversight for this study is provided by the University of Maryland, Baltimore and University of Maryland, College Park Institutional Review Boards. Additionally, the study protocol is reviewed annually by an independent Data and Safety Monitoring Board. Study results will be disseminated via research conference presentations and peer-reviewed publications.Trial registration number NCT02941809.https://bmjopen.bmj.com/content/9/6/e026604.full |
| spellingShingle | Annabelle M Belcher Thomas O Cole Aaron D Greenblatt Stephen W Hoag David H Epstein Michael Wagner Amy S Billing Ebonie Massey Kristen R Hamilton Zofia K Kozak Christopher J Welsh Eric Weintraub Emerson M Wickwire Eric D Wish Ted J Kaptchuk Luana Colloca Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment BMJ Open |
| title | Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment |
| title_full | Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment |
| title_fullStr | Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment |
| title_full_unstemmed | Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment |
| title_short | Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment |
| title_sort | open label dose extending placebos for opioid use disorder a protocol for a randomised controlled clinical trial with methadone treatment |
| url | https://bmjopen.bmj.com/content/9/6/e026604.full |
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