Opioid Addiction, Opioid Dependence, Opioid-Related Disorders, Opioid Withdrawal
Conditions
Brief summary
The Bridge Device (BD) is a neuromodulator medical device that has been cleared by the FDA for Opioid Use Disorder (OUD) treatment. Importantly, medical devices reviewed by the FDA are cleared (based on safety) rather than approved (based on efficacy), which means the BD did not need to demonstrate efficacy before it became commercially available. As a result, the device was not required to have a sham-controlled trial for FDA clearance and there is no active research, to the investigators' knowledge, that specifically addresses the degree to which opioid withdrawal can be treated through neuromodulation. To rigorously evaluate the efficacy of the BD for treating OUD, the investigators will enroll persons with active OUD, not currently receiving medications for OUD. Participants will be recruited and admitted to the Clinical Research Unit (CRU) for a 2-3 week period. During participants' residential stay, participants will be stabilized for 7-11 days on four times daily morphine (30 mg, SC) and undergo a precipitated withdrawal challenge using the opioid antagonist naloxone, approximately \>= 4 days of morphine maintenance. This is a standard practice for the investigators' study and allows the investigators to objectively assess dependence. The BD and study medication will begin following morphine stabilization. Participants will be randomly assigned to one of three conditions (1) active BD with placebo (BD/P), (2) sham BD with lofexidine (SBD/L), or (3) sham BD and placebo (SBD/P). Participants will use the BD for 5 days and will receive study drug for 7 days. Participants will be monitored for an additional 4 days after device removal to determine whether withdrawal resumes. Participants will undergo a second naloxone challenge after removal of the device/capsule completion to verify lack of opioid tolerance and will be encouraged to begin treatment with oral naltrexone followed by extended release naltrexone. Throughout the residential stay, all participants will be given referral to and assisted with engaging in outpatient treatment following study discharge.
Interventions
DEVICEBridge Device
An FDA-cleared neuromodulator medical device, marketed for the treatment of opioid withdrawal
DRUGLofexidine
FDA-approved medication for the treatment of opioid withdrawal. Participants will receive capsules 4 times daily for 7 days. The active dose is 0.72 mg four times daily for Days 1-5, for a total daily dose of 2.88 mg. Doses on Days 6 and 7 will be 1.44 (2 active, 2 placebo capsules) and 0.72 mg (1 active, 3 placebo capsules), respectively.
DRUGPlacebo
Inactive study drug, encapsulated to look like the active study drug. Participants will receive capsules 4 times daily for 7 days.
DEVICESham Bridge Device
Inactive Bridge Device which is applied and looks identical to the active Bridge Device
Sponsors
Johns Hopkins University
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
The study is of a device (the Bridge Device), not of a drug.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 18 and 65 years old * Meets Diagnostic and Statistical Manual-5 criteria for Opioid Use Disorder (OUD) (moderate or severe) based upon Mini-International Neuropsychiatric Interview (MINI) * Provides a urine sample that tests positive for opioids during screening or have evidence of opioid withdrawal * Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests * No significant psychiatric illnesses besides OUD * Seeking treatment to stop using illicit opioids * Willing to comply with the study protocol * Have no clinically significant chronic medical or surgical disorders or conditions that are judged by the investigators to prevent participation
Exclusion criteria
* Pregnant or breast feeding * Receiving opioid agonist treatment * Significant medical illness (e.g., insulin dependent diabetes) * Significant psychiatric illness (e.g., schizophrenia) * Use of medical cannabis * Contraindications for use of the Bridge Device, morphine, lofexidine or naloxone (e.g., hemophilia, psoriasis and other skin conditions, a cardiac pacemaker) * Have evidence of physical dependence on alcohol or benzodiazepines that requires medical detoxification * Hypotension (diastolic blood pressure of less than 60 mm Hg or systolic blood pressure of less than 90 mm Hg on screening examination) * Prolonged corrected QT interval interval on screening ECG (defined as \>0.44 seconds for males and \>0.46 seconds for females) * Hepatic or renal impairment, as indicated by the following lab results at the screening session: * Aspartate aminotransferase or alanine transaminase \>3x upper limit of normal (ULN) * Total Bilirubin \>2x ULN. * Creatinine \>1.5x ULN. * Treatment with a strong 2D6 inhibitor (e.g., paroxetine, thioridazine, cinacalcet, bupropion, methotrimeprazine, fluoxetine, midostaurin, propafenone, glycerol phenylbutyrate, halofantrine, cisapride, dacomitinib, orphenadrine, quinidine) * Have a known allergy to any of the study medications * Have circumstances that would interfere with study participation (e.g., impending jail)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Retained | Up to 5 days | The number of participants retained (dichotomous: retained, not retained) during the 5 day intervention. Greater retention is indicative of a better treatment outcome. |
| Withdrawal Severity as Measured by Clinical Opiate Withdrawal Scale (COWS) Peak Score | At the end of day 5 | Peak COWS Score (range: 0-48). Lower peak COWS scores are indicative of better withdrawal suppression. |
| Withdrawal Severity as Measured by Area Under the Curve for COWS Score From Days 1-5 of Active Study Intervention | Four times a day (0800, 1200, 1600, 2000) on each of days 1-5 | Area under the curve COWS scores (range: 0-240). Smaller area under the curve COWS scores are indicative of better withdrawal suppression. |
| Withdrawal Severity as Measured by COWS Peak Daily Score | Up to 5 days | Peak daily COWS score (range: 0-48). Lower peak daily COWS scores are indicative of better withdrawal suppression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Retained | At the end of day 9 | The number of participants who are retained (dichotomous: retained, not retained) during the 9 day intervention. Greater retention is indicative of better intervention outcome. |
| Withdrawal Severity as Measured by the SOWS Peak Daily Score | Up to day 5 | Peak SOWS Score (range: 0-64). Lower peak SOWS scores are indicative of better withdrawal suppression. |
| Withdrawal Severity as Measured by Area Under the Curve SOWS Score | Four times a day (0800, 1200, 1600, 2000) days 1-5 | Area under the curve SOWS scores (range: 0-320). Smaller area under the curve SOWS scores are indicative of better withdrawal suppression. |
| Withdrawal Severity as Measured by the Subjective Opiate Withdrawal Scale (SOWS) Peak Score | End of Day 5 | Peak daily SOWS score (range: 0-64). Lower peak daily SOWS scores are indicative of better withdrawal suppression. |
| Number of Participants Who Initiate Naltrexone at the End of the Study | At the end of day 9 | The number of participants who initiate naltrexone (dichotomous: yes, no) at the end of day 9. A larger number of participants is indicative of better naltrexone initiation success. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREric Strain
Johns Hopkins University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 11 / 12 | 10 / 12 | 10 / 12 |
| serious Total, serious adverse events | 3 / 12 | 0 / 12 | 0 / 12 |
Outcome results
None listed