Opioid-use DisorderNCT02941809
Harnessing Placebo Effects in Methadone Treatment
A study of Opioid-use Disorder and Opioid-Related Disorders, run by University of Maryland, Baltimore at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid-use Disorder, Opioid-Related Disorders
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 133 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2017to 31 Jul 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (age 18 or over)
- Newly-admitted to the methadone treatment program
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Maryland Methadone Treatment Center
Baltimore, Maryland, 21201
About this study
Official title: 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.
Read the 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.
- Conditions
- Opioid-use Disorder, Opioid-Related Disorders
- Being tested
- Open-Label Placebo (OLP)
- Keywords
- medications for opioid use disorder, methadone
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Open-Label Placebo (OLP)Behavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Open-Label Placebo (OLP) | Experimental | 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. Receives: Behavioral: Open-Label Placebo (OLP) |
| Treatment as Usual (TAU) | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Three months (90 days)
Secondary outcomes (9)
Treatment Retention
Three-month (90-day) and 6-month (180 day) treatment retention as a binomial (yes/no) variable outcome
Measured: 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
Measured: 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".
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (entry into treatment), and 1- and 3-months post-baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2016 (estimated)
- Study start5 Dec 2017
- Primary completion31 Jul 2020
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Opioid-use DisorderStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 133 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, College Park
- Responsible party
- Principal investigator, Annabelle Belcher, University of Maryland, Baltimore
- Investigators
- Annabelle M Belcher, PhD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02941809
- Sponsor's protocol ID
- HP-00070829
- Status last verified
- Aug 2020
- First submitted
- 19 Oct 2016
- Last updated
- 11 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31230007Cai 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.
PubMed 30913037Belcher AM, Hamilton-Moseley KR, Massey E, Yoon M, Cole TO, Wagner MD, Billing AS, Greenblatt AD, Weintraub E, Wish ED. Trait impulsivity prospectively predicts lower methadone treatment retention: moderation by pain catastrophizing. Addict Sci Clin Pract. 2026 Jul 10. doi: 10.1186/s13722-026-00699-7. Online ahead of print.
PubMed 42432774Belcher AM, Cole TO, Massey E, Billing AS, Wagner M, Wooten W, Epstein DH, Hoag SW, Wickwire EM, Greenblatt AD, Colloca L, Rotrosen J, Magder L, Weintraub E, Wish ED, Kaptchuk TJ. Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237099. doi: 10.1001/jamanetworkopen.2023.7099.
PubMed 37043203
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-labeled Dose-extending Placebos as an Adjunct to Methadone Treatment: A Pilot Study
- ClinicalTrials.gov ID
- NCT02941809
- Acronym / sponsor ID
- HP-00070829
- Conditions
- Opioid-use Disorder, Opioid-Related Disorders
- Keywords
- medications for opioid use disorder, methadone
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 133 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- University of Maryland, College Park
- Study start
- 5 Dec 2017 (actual)
- Primary completion
- 31 Jul 2020 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 21 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Open-Label Placebo (OLP) | Experimental | Behavioral: 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. |
| Treatment as Usual (TAU) | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult (age 18 or over)
- Newly-admitted to the methadone treatment program
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Behavioural | Open-Label Placebo (OLP) |
Primary outcome
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.
9 secondary outcomes
Treatment Retention
Time frame: 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)
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.
Urine Testing- Quick-tox Screen
Time frame: Baseline
Craving assessment
Time frame: 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.
Subjective Opioid Withdrawal Scale (SOWS)
Time frame: 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
World Health Organization Quality of Life - Brief (WHOQOL-BREF) Assessment
Time frame: Baseline (entry into treatment), and 1- and 3-months post-baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Background: PubMed 31230007Belcher 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.
- Background: PubMed 30913037Cai 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.
- Derived from this study: PubMed 42432774Belcher AM, Hamilton-Moseley KR, Massey E, Yoon M, Cole TO, Wagner MD, Billing AS, Greenblatt AD, Weintraub E, Wish ED. Trait impulsivity prospectively predicts lower methadone treatment retention: moderation by pain catastrophizing. Addict Sci Clin Pract. 2026 Jul 10. doi: 10.1186/s13722-026-00699-7. Online ahead of print.
- Derived from this study: PubMed 37043203Belcher AM, Cole TO, Massey E, Billing AS, Wagner M, Wooten W, Epstein DH, Hoag SW, Wickwire EM, Greenblatt AD, Colloca L, Rotrosen J, Magder L, Weintraub E, Wish ED, Kaptchuk TJ. Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237099. doi: 10.1001/jamanetworkopen.2023.7099.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annabelle M Belcher, PhD principal investigator
University of Maryland, Baltimore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Opioid-use Disorder and Opioid-Related Disorders, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Three-month dose of methadone (time frame: Three months (90 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02941809, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.