Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03769025 |
| Other study ID # |
RODS |
| Secondary ID |
5U34DA045177-03 |
| Status |
Completed |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2019 |
| Est. completion date |
July 1, 2022 |
Study information
| Verified date |
July 2023 |
| Source |
University of Pennsylvania |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a 15-week, outpatient study of remote observed dosing to improve suboxone compliance
in opiate dependent subjects.The main purpose of this study is to see if watching patients
take their medication will improve treatment of opiate dependence by prompting patients to
take all prescribed doses of Suboxone. Suboxone is approved by the Food and Drug
Administration (FDA) for the treatment of opiate dependence. All patients receive a
smartphone and patients in the intervention (remote observed dosing) group will use the
smartphone to take videos of themselves taking Suboxone.
Description:
Opioid use disorder (OUD) is a significant public health problem. About 2 million Americans
meet criteria for opioid use disorder involving prescription pain relievers and an additional
591,000 Americans meet criteria for a heroin use disorder. The rise in prescription opioid
use in the US has resulted in a dramatic increase in heroin use, as prescription opioid users
switch to heroin when their access to prescription opioids become less available. Opioids
(including prescription opioids and heroin) killed more than 33,000 people in 2015, more than
any year on record. Nearly half of all opioid overdose deaths involve a prescription opioid.
Buprenorphine, a partial agonist that exerts significant actions at the mu opioid receptor,
has been shown to be effective for the treatment of OUD. Because it is a partial agonist and
not prone to overdose, it is considered to be safe enough to dispense out of a clinician's
office as opposed to an opiate treatment program (OTP). The availability of buprenorphine
treatment outside of an OTP has significantly expanded the availability of effective
treatment for OUD and is associated with reducing disparities related to treatment access.
While initial studies reported little evidence of buprenorphine diversion, more recent
studies have indicated buprenorphine is prone to diversion and poor adherence that can
significantly diminish its safety and efficacy. In these US clinical trials, adequate
adherence to buprenorphine has been shown to occur in fewer than 50% of subjects who are
prescribed the medication. In a trial involving 50 African American subjects with opioid use
disorder participating in office based buprenorphine treatment, it was found that only 48% of
the subjects were adherent to the medication as defined as having 80% or more of their visits
associated with a positive UDS for buprenorphine. In another trial involving 703 subjects
with opioid use disorder only 41% of the subjects took buprenorphine 80% of the days it was
prescribed. Finally in an examination of medical and pharmacy claims data over a year, only
32% of patients participating in office based buprenorphine treatment took buprenorphine on
80% or more days.
Efforts to reduce poor adherence and diversion in buprenorphine maintenance generally include
smaller prescriptions and more frequent office visits. An alternative to frequent face to
face meetings is using smartphone technology to conduct remote observation of dosing (ROD).
In addition, OUD patients have expressed that observed dosing of MMT and flexible dose
prescription regimes play an important role in their treatment. However, there have been no
published studies using ROD to monitor compliance of Suboxone.
Remote Observed Dosing Intervention We conducted a Stage 1B integrated cellphone based
behavioral intervention that visually confirmed medication ingestion, thereby potentially
reducing buprenorphine misuse and diversion and improving medication adherence. Patients with
OUD, who were not currently prescribed buprenorphine, were recruited. All patients received
buprenorphine, a study provided smartphone, weekly Cognitive Behavioral Therapy (CBT), and
twice weekly urine screens. The experimental group video recorded themselves taking the
medication and these videos were automatically sent daily to the clinical research staff who
observed the dosing. This allowed for both the patients and clinical staff to find convenient
times to do the tasks and improved clinic office workflow. The attention control (AC) group
did not record their medication dosing.
Participants and Recruitment Participants and Eligibility. This study involved individuals
with Opioid Use Disorder (OUD) who received three months (12 weeks) of burpenorphine
(Suboxone) (standard dose will be up to 16 mgs/day, adjusted as necessary on an individual
basis).
Procedures: Patient and Clinical Data Collection Screening Procedures, Suboxone Induction and
Randomization. Potential participants will be screened for physical and psychological
appropriateness for inclusion in the study using standard intake procedures. Participants who
are appropriate for the trial will be inducted onto Suboxone using standard office based
induction as described in the ASAM National Practice Guideline for the Use of Medications in
the Treatment of Addiction Involving Opioid Use.
Participants will be randomized into one of two study groups based on proportion of use of
prescription opiates and heroin, gender, and prior Suboxone treatment. Both groups will
receive standard buprenorphine maintenance treatment. Participants will attend study visits
twice weekly for 12 weeks. One group will be assigned to Remote Observed Dosing (ROD) and
will have all of their Suboxone doses remotely observed using procedures described below. The
attention control (AC) group will not have their dosing observed but will send a video
message not associated with dosing to the study team daily matching contact time with the
study team.
Remote Observed Dosing Compliance. During the start-up phase of the project, we will record a
short 5 min instruction video that will be stored on participants' cellphones and on our
study web-site that will detail how to take the dosing video and how to ensure it was
uploaded correctly. Clinical staff and participants will also be able to use a HIPAA
compliant texting service to arrange appointments, send reminders and discuss any study
related issues that arise. Note: Participants in the control condition will be provided with
a list of prompts and asked to pick one prompt daily to record a video on. They will then
follow the same procedures as the experimental condition.
Step 1: Using the study provided smartphone a participant in the experimental condition will
use the front facing camera to record taking their study medication.
Step 2: The participant will remove the day's Suboxone dose from their pill pack, place the
dose (film) under their tongue and remain with their head in view of the camera until the
film dissolves completely. They will then open their mouth, raising their tongue to the roof
to ensure the dosage has been dissolved.
Step 3: The participant will end the recording. The phone will automatically save the video
onto the micro-sd card and the video will be automatically sent to a secure study server.
Once the video is uploaded, a notification message will appear on the participant's phone and
the study team will be notified a video has been uploaded. Each recording is expected to last
approximately 5 minutes. Note: by saving the video on the micro-sd card, we are safeguarding
in the event there is a "bad connection" or "user error" in the video uploading to the
server. Phones will be locked with a passcode and if a phone is lost/stolen, it will be
"wiped" clean remotely. In addition, a Certificate of Confidentiality will be requested for
this research study.
Step 4: Clinical staff will view the video daily. Any instances where the subject moves out
of camera view will be recorded as a day without dosing. If the video is not uploaded and is
not saved on the micro-sd card, it too will be recorded as a day without dosing.
Step 5: Clinical staff and participants will use a HIPAA compliant text messaging service to
communicate. Even though we will train participants on how to take and send dosing videos, we
anticipate there will be a slight learning curve. During this time, clinical staff will
communicate with participants on how to record the dosing.
All patients who are enrolled will receive a smartphone that includes unlimited talk, text
and data. The smartphones will be used to communicate with patients for appointments, make
reminder calls, discuss any study related issues, and to record and send the study videos.
All patients will be instructed on smartphone use, security and on how to use the phones to
record and send the videos to the study team. They will also be instructed about how to take
Suboxone and ROD patients will receive additional training on how to ensure the observed
dosing video is recorded and uploaded correctly.
Suboxone Dosing. After induction, all patients will receive open-label Suboxone for 12 weeks.
Patients in both groups will receive a weeks' worth of Suboxone at each medication management
visit. After the 12 weeks of Suboxone, subjects will be referred to on-going treatment
options in the community or will be tapered from Suboxone if they so desire.
Cognitive Behavioral Relapse Prevention. In addition to study medication, subjects will
participate in weekly, manualized, individual cognitive behavioral relapse prevention
psychotherapy. They will also receive weekly Medication Management (MM), adapted for MAT for
opioid use disorder.
Weekly visits. Patients will be seen twice weekly. For each in-office visit, patients will
provide a urine sample that will be tested for drugs of abuse and for quantitative
buprenorphine and norbuprenorphine levels. At each office visit, patients will also complete
questionnaires on mood, craving and general health. They will be asked about other
medications they are using, about their drug and alcohol use since their last visit, and
about any side effects they may be experiencing. Dosage adjustments will be made as needed at
the discretion of their clinician.
Medication adherence will be monitored by self-report and verified with creatinine normalized
quantitative urinary buprenorphine and norbuprenorphine levels. Urine was chosen as opposed
to blood levels to verify adherence for several reasons. First the high number of samples
needed to verify adherence over the course of a twelve-week trial would present a great
burden to the study patients. Frequent venipunctures can be difficult in patients with opioid
use disorder who have a history of IV use of opioids. Creatinine normalized quantitative
urine medication levels have been used successfully to verify medication adherence in trials
involving both methadone and buprenorphine.
Measures Columbia Suicide Severity Rating Scale (C-SSRS). This is a 5-item scale with
additional questions that may be asked based on the participant's responses to the core
items. This questionnaire will assess both lifetime and recent suicidal ideation and
behavior, including both passive and active thoughts/plans. This data will not be analyzed
but will be included to help ensure the safety of the participants.
Timeline Follow Back Interview (TLFB). (The TLFB is a 15-30 minute, semi-structured interview
adapted by our laboratory to collect information about daily drug, alcohol, and nicotine use.
The TLFB will be given by trained research staff at baseline to cover 3 months immediately
preceding treatment entry and will be updated at each research visit to determine any time
spent in a controlled environment and cocaine, nicotine, and other drug use during the period
since the last visit.
Video Compliance. Submission of videos will be recorded (date and time) and assessed daily
for compliance (ie., taking the medication as prescribed). In addition, videos will be saved
off the micro-sd cards at each office visit.
Laboratory Measurements (in alphabetical order) Pregnancy Testing. Urine pregnancy tests will
be obtained from all women at baseline, week 5, week 9, and end of study.
Quantitative urine buprenorphine and norbuprenorphine levels (using gas chromatography) with
urine creatinine used as a control for urinary concentration will be assessed twice weekly
throughout the trial. Qualitative (emit) urine toxicology for other drugs (benzodiazepines,
barbiturates, opiates, marijuana, methadone, and amphetamine) is done at baseline and weekly
throughout the trial.
DATA ANALYSIS For the ROD group, we will calculate the within-patient proportion of study
days on which video captured adherence, as per protocol. The primary comparison between the
groups will use the creatinine normalized weekly quantitative urine levels for buprenorphine
and norbuprenorphine. The main explanatory variable will be a binary indicator for group (ROD
vs AC). Our primary analyses will examine the two sets of responses (buprenorphine and
norbuprenorphine) separately.
Exploratory Aims Rates of illicit opiate use will be compared between the groups using urine
drug screens (UDS) obtained at each visit. A study week will be classified as a "non-use"
week if both UDS tests are available and are negative for opiates and if the participant
self-reports no use; a study week with a positive UDS or a self-report of use will be
classified as a "use" week; study weeks with incomplete data and no test or report of use
will be regarded as missing. The number of non-use weeks will be compared.
