Opioid-use Disorder
Conditions
Brief summary
The investigators will conduct a phase I study involving 41 participants selected randomly among patients prescribed buprenorphine-naloxone for opioid misuse as a feasibility trial of the study of the Pillsy device. The study will track the effectiveness of the Pillsy technology and associated smartphone application by measuring adherence to buprenorphine-naloxone therapy and patient satisfaction with the application and the Pillsy device.
Detailed description
The purpose of this randomized, controlled trial in Phase I is to determine whether the Pillsy intervention can improve adherence to buprenorphine-naloxone compared to Service As Usual. This will be a collaborative study between WSU, Pillsy, Inc, and the clinical site Ideal Options (opioid use and other substance use disorders treatment center). The overarching goal is to evaluate if the use of the Pillsy system will improve treatment adherence. The study coordinator will work closely with the clinical site, conducting a scripted screening, by phone or in person, documenting substance use, addiction treatment history, medical and psychiatric history, medication, addiction treatment goals, and availability of social support. The Pillsy device is a smart cap that tracks pill bottle openings and uses lighted reminders to prompt patients when to take their medication. The Pillsy Helper feature is a smartphone application that sends text and phone reminders as well as links to the participant named family and friend support networks. The Pillsy Helpers feature allows participants to name friends and family members who will also receive a text message notification 1 hour after a missed dose to reach out to offer support. In addition, the prescriber will be contacted when the patient has missed a dose, giving the prescriber the opportunity to intervene. Study participants will be randomized to one of two groups. The control group will receive the Pillsy cap alone. The active group will receive the Pillsy cap and smartphone application with associated benefits. To measure adherence, all participants will provide a urine sample at each study visit and complete a questionnaire (ex: AUDIT, Fagerstrom, Addiction Severity Index, Timeline Follow-Back) and survey that assesses their satisfaction with treatment.
Interventions
BEHAVIORALReminders messages to improve adherence.
If the participant does not take their medicine at the correct time, a light on the smart pill cap begins to flash. If the bottle is not opened within 20 minutes, the Pillsy application sends an SMS text reminder to the participant's phone. If the bottle is not opened within 60 minutes, the participant receives an automated phone call. The participant may also receive brief motivational phrases or craving surveys that can be tailored to participant needs and preferences. Also, based on pre-populated and adjustable craving and withdrawal levels, the participants' provider could be contacted automatically based on the thresholds being crossed. Pillsy also includes a Pillsy Helpers feature in which the patient can name friends and family members who will also receive a text message notification one hour after a missed dose.
Sponsors
National Institute on Drug Abuse (NIDA)
Washington State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Subject can and has signed an Institutional Review Board (IRB) approved informed consent form (ICF). * Age ≥18 and ≤60 years. * Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for Opioid use disorder (OUD). * In the professional opinion of the prescribing provider, the patient requires buprenorphine-naloxone for Opioid use disorder. * Owns a working smartphone. * Agrees to abstain from opioids other than Opioid Agonist Therapy (OAT) during the study. * Able to read and speak English. * Can identify one study partner/caregiver who agrees to participate.
Exclusion criteria
* Have been prescribed chronic OAT treatment in the previous 12 months. * Have known hypersensitivity to buprenorphine and/or naloxone. * Are pregnant or lactating women or women of childbearing potential who are not using any form of birth control. * Have a primary diagnosis of substance use disorder other than OUD or nicotine. * Require opioids for the treatment of chronic pain. * Have evidence of coagulopathy within 90 days prior to enrollment. * Have clinically significant thrombocytopenia. * Have screening serum aspartate (AST) and alanine aminotransferase (ALT) levels 3-fold higher than upper limits of normal. * Have screening total bilirubin or creatinine levels 1.5-fold higher than the upper limits of normal. * Use of other medications that are known to affect the outcome measures in this study including methadone. * Are unable to provide voluntary informed consent. * Have pending legal issues that could adversely affect the participant's freedom to participate. * Cannot read or speak English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Medication Possession Ratio | 12 weeks | Change in adherence to buprenorphine-naloxone treatment assessed by medication possession ratio (MPR). This was calculated as mean over the course of the trial. MPR is the sum of the days' supply for all fills of a given drug in a particular time period, divided by the number of days in the time period (time period varies based on length of prescription given by provider). MPR is typically expressed as a percentage, however below we express it as the result of the fraction. This measurement was based on pharmacy fills (days supply). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Week 1, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | Week 1 | Week 1 Pillsy Satisfaction Survey. Yes vs No question: Are you satisfied with the Pillsy system overall?. Outcome data measured is count of participants endorsing yes. |
| Number of Days Participant Self-reported Other Substance Use | 12 weeks | Participant self-report of other substance use (alcohol, cigarettes, and illicit opioids) is assessed with Timeline Follow-back measure |
| Participant Engagement | 12 weeks (Assessed at screening visit, week 1 visit, week 6 visit and week 12 visit) | Participant engagement quantified through days of retention in treatment. |
| Week 6, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | Week 6 | Week 6 Pillsy Satisfaction Survey. Yes vs No question: Are you satisfied with the Pillsy system overall? Outcome data measured is count of participants endorsing yes. |
| Week 12, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | Week 12 | Week 12 Pillsy Satisfaction Survey. Yes vs No question: Are you satisfied with the Pillsy system overall? Outcome data measured is count of participants endorsing yes. |
| Change in Use of Non-prescribed Opioids | 12 weeks | Use of non-prescribed opioids is assessed via urinalysis (UA) by the treatment team at Ideal Option, as a standard of care. Ideal Option will share this data with the study team (through signed data use agreement). Our study team will evaluate change in use of non-prescribed opioids over the course of the study, based on the data provided by the clinic. Below it is expressed as the mean number of illicit opioid positive UAs submitted out of the total number of UAs submitted for each arm. |
Countries
United States
Participant flow
Recruitment details
All participants were recruited from Buprenorphine and Buprenorphine/Naloxone clinics in the NW USA region
Pre-assignment details
84 individuals were assessed for eligibility, of these 41 were randomized
Participants by arm
| Arm | Count |
|---|---|
| Pillsy Arm Participants in the Pillsy arm will receive a prescription for buprenorphine-naloxone with an ''active'' Pillsy smart cap that will continuously collect data on pill bottle openings, missed doses, text messages sent, automated phone calls made. A participant who misses an entire day of buprenorphine-naloxone will automatically receive a survey about cravings and risk of relapse.
Reminders messages to improve adherence.: If the participant does not take their medicine at the correct time, a light on the smart pill cap begins to flash. If the bottle is not opened within 20 minutes, the Pillsy application sends an SMS text reminder to the participant's phone. If the bottle is not opened within 60 minutes, the participant receives an automated phone call. The participant may also receive brief motivational phrases or craving surveys that can be tailored to participant needs and preferences. Also, based on pre-populated and adjustable craving and withdrawal levels, the participants' provider could be contacted automatically based on the thresholds being crossed. Pillsy also includes a Pillsy Helpers feature in which the patient can name friends and family members who will also receive a text message notification one hour after a missed dose. | 19 |
| Service as Usual Arm Participants in the Service As Usual arm will receive a prescription for buprenorphine-naloxone with an ''inactive'' Pillsy smart cap that will track openings but will not provide reminders or any other messaging. They will receive a basic application that can deploy patient satisfaction surveys. | 22 |
| Total | 41 |
Baseline characteristics
| Characteristic | Pillsy Arm | Service as Usual Arm | Total |
|---|---|---|---|
| Age, Continuous | 36.1 years STANDARD_DEVIATION 8.1 | 37.7 years STANDARD_DEVIATION 11 | 36.9 years STANDARD_DEVIATION 9.7 |
| Baseline Opioid Use Disorder (OUD) Diagnostic and Statistical Manual (DSM) Diagnosis Mild | 9 Participants | 5 Participants | 14 Participants |
| Baseline Opioid Use Disorder (OUD) Diagnostic and Statistical Manual (DSM) Diagnosis Moderate | 0 Participants | 2 Participants | 2 Participants |
| Baseline Opioid Use Disorder (OUD) Diagnostic and Statistical Manual (DSM) Diagnosis Severe | 10 Participants | 15 Participants | 25 Participants |
| Employment Employed | 8 Participants | 9 Participants | 17 Participants |
| Employment Unemployed | 11 Participants | 13 Participants | 24 Participants |
| Last Buprenorphine Initiation 0 to 30 days ago | 5 Participants | 8 Participants | 13 Participants |
| Last Buprenorphine Initiation 31 to 60 days ago | 2 Participants | 1 Participants | 3 Participants |
| Last Buprenorphine Initiation 60 to 90 days ago | 2 Participants | 1 Participants | 3 Participants |
| Last Buprenorphine Initiation 91 to 120 days ago | 9 Participants | 11 Participants | 20 Participants |
| Last Buprenorphine Initiation Missing | 1 Participants | 0 Participants | 1 Participants |
| Last Buprenorphine Initiation Not Eligible | 0 Participants | 1 Participants | 1 Participants |
| Marital Status Divorced | 5 Participants | 4 Participants | 9 Participants |
| Marital Status Married | 9 Participants | 3 Participants | 12 Participants |
| Marital Status Single | 5 Participants | 15 Participants | 20 Participants |
| Race/Ethnicity, Customized American Indian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Prefer not to say | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 20 Participants | 36 Participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Male | 7 Participants | 12 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 22 |
| other Total, other adverse events | 0 / 19 | 0 / 22 |
| serious Total, serious adverse events | 0 / 19 | 0 / 22 |
Outcome results
Primary
Mean Medication Possession Ratio
Change in adherence to buprenorphine-naloxone treatment assessed by medication possession ratio (MPR). This was calculated as mean over the course of the trial. MPR is the sum of the days' supply for all fills of a given drug in a particular time period, divided by the number of days in the time period (time period varies based on length of prescription given by provider). MPR is typically expressed as a percentage, however below we express it as the result of the fraction. This measurement was based on pharmacy fills (days supply).
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pillsy Arm | Mean Medication Possession Ratio | 0.839 Medication supply / days in time period | Standard Deviation 0.652 |
| Service as Usual Arm | Mean Medication Possession Ratio | 0.752 Medication supply / days in time period | Standard Deviation 0.713 |
Secondary
Change in Use of Non-prescribed Opioids
Use of non-prescribed opioids is assessed via urinalysis (UA) by the treatment team at Ideal Option, as a standard of care. Ideal Option will share this data with the study team (through signed data use agreement). Our study team will evaluate change in use of non-prescribed opioids over the course of the study, based on the data provided by the clinic. Below it is expressed as the mean number of illicit opioid positive UAs submitted out of the total number of UAs submitted for each arm.
Time frame: 12 weeks
Population: Participants in both groups (Pillsy and SAU) were asked by their medical provider frequently to provide urine samples as part of their standard of care treatment. This was not on a set schedule. Results of all urinalyses were provided to the research team for analysis to evaluate change in use of non-prescribed opioids over the course of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pillsy Arm | Change in Use of Non-prescribed Opioids | 2.17 Urinanalysis | Standard Deviation 7.25 |
| Service as Usual Arm | Change in Use of Non-prescribed Opioids | 1.68 Urinanalysis | Standard Deviation 4.39 |
Secondary
Number of Days Participant Self-reported Other Substance Use
Participant self-report of other substance use (alcohol, cigarettes, and illicit opioids) is assessed with Timeline Follow-back measure
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pillsy Arm | Number of Days Participant Self-reported Other Substance Use | Alcohol | 0.82 Days of use | Standard Deviation 3.89 |
| Pillsy Arm | Number of Days Participant Self-reported Other Substance Use | Cigarettes | 7.83 Days of use | Standard Deviation 12.81 |
| Pillsy Arm | Number of Days Participant Self-reported Other Substance Use | Illicit opioids | 0.33 Days of use | Standard Deviation 2.04 |
| Service as Usual Arm | Number of Days Participant Self-reported Other Substance Use | Alcohol | 0.24 Days of use | Standard Deviation 0.83 |
| Service as Usual Arm | Number of Days Participant Self-reported Other Substance Use | Cigarettes | 9.02 Days of use | Standard Deviation 13.06 |
| Service as Usual Arm | Number of Days Participant Self-reported Other Substance Use | Illicit opioids | 0.45 Days of use | Standard Deviation 2 |
Secondary
Participant Engagement
Participant engagement quantified through days of retention in treatment.
Time frame: 12 weeks (Assessed at screening visit, week 1 visit, week 6 visit and week 12 visit)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pillsy Arm | Participant Engagement | 71.3 Days | Standard Deviation 28.2 |
| Service as Usual Arm | Participant Engagement | 52.6 Days | Standard Deviation 38.8 |
Secondary
Week 12, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System
Week 12 Pillsy Satisfaction Survey. Yes vs No question: Are you satisfied with the Pillsy system overall? Outcome data measured is count of participants endorsing yes.
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pillsy Arm | Week 12, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | 11 Participants |
| Service as Usual Arm | Week 12, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | 12 Participants |
Secondary
Week 1, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System
Week 1 Pillsy Satisfaction Survey. Yes vs No question: Are you satisfied with the Pillsy system overall?. Outcome data measured is count of participants endorsing yes.
Time frame: Week 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pillsy Arm | Week 1, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | 14 Participants |
| Service as Usual Arm | Week 1, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | 17 Participants |
Secondary
Week 6, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System
Week 6 Pillsy Satisfaction Survey. Yes vs No question: Are you satisfied with the Pillsy system overall? Outcome data measured is count of participants endorsing yes.
Time frame: Week 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pillsy Arm | Week 6, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | 14 Participants |
| Service as Usual Arm | Week 6, Number of Participants Satisfied With Pillsy Usability and Reminder Feedback System | 11 Participants |