Assessing Dose Taken in Opioid Use Disordered Patients With an Electrochemical Sensor

Study Overview
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Brief Summary
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CARI Health aims to develop a methadone dose taken sensor that provides real-time data on interstitial fluid (ISF) levels that could be used as a methadone adherence monitor for daily doses. Use of such a monitor would allow for the physician, counselor, patient, and family member to remotely verify that a physician prescribed dose has been taken. Such a verification system can allow methadone clinics greater flexibility in the provision of take-home doses and thus retain more patients in the clinic.

Detailed Description
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Three specific phases and 9 aims are proposed for first-in-human studies of a remote medication monitor for dose taken in patients taking methadone for opiate use disorder. Phase 1 detection over 3-6 hours (N=10) Aim 1: Detect methadone and one or more of its metabolites in interstitial fluid (ISF) with differential pulse voltammetry (DPV) Aim 2: Correlate in vitro blood-based LC-MS and DPV Scans with Intradermal Microneedle based DPV Scans Aim 3: Accurately identify that a dose of methadone has been taken Aim 4: Determine the frequency and severity of any adverse events up to 6 hours. Phase 2 detection over 12 hours (N=15) Aim 5. Quantitate methadone and one or more of its metabolites in ISF with DPV over 12 hrs. Aim 6: Determine the frequency and severity of any adverse events up to 12 hours Phase 3 detection over 3 days N=20 ( 15 single dosed subjects, 5 split dosed subjects ) Aim 7. Quantitate methadone and one or more of its metabolites in ISF with DPV over 3 days. Aim 8. Accurately identify a dose or half a dose has been taken Aim 9: Determine the frequency and severity of any adverse events up to 3 days

Official Title
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Assessing Dose Taken in Opioid Use Disordered Patients With an Electrochemical Sensor

Conditions
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Adherence, Medication, Opioid Use Disorder

Intervention / Treatment
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* Device: Remote Medication Monitor (RMM) - Prototype
* Drug: Daily Methadone Dose


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for methadone group includes: Age 18-70. A prescription for liquid methadone at a dose of 10mg or more. Taken methadone as prescribed in the last 2 days. Has been prescribed at least 3 take homes Exclusion criteria for methadone group includes: Age <18 or >70. A condition preventing or complicating ISF collection. Conditions may include dermatological (skin) condition, immunodeficiency, bleeding diathesis, recent blood donation, anemia, cancer, congestive heart failure, or tuberculosis. Any active severe depression (e.g., suicidal ideation) or mania symptoms. Pregnancy, or intending to become pregnant during the course of the study. Patients determined to be unstable for enrollment or take homes by the Outpatient Treatment Program (OTP). Under a conservatorship.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 3-6 HRS<br>Microneedle electrode array placed into dermis for up to 6 hours. DPV Scans performed at a frequency of 1-20 per hour. | Device: Remote Medication Monitor (RMM) - Prototype<br>* Inserted Microneedle Electrode Array for assaying dermal interstitial fluid.<br>* Other names: RMM;Drug: Daily Methadone Dose<br>* patient takes their prescribed daily dose of methadone<br>* Other names: Dose Taken;|
| 12 HRS<br>Microneedle electrode array placed into dermis for up to 12 hrs. DPV Scans performed at a frequency of 1-20 per hour. | Device: Remote Medication Monitor (RMM) - Prototype<br>* Inserted Microneedle Electrode Array for assaying dermal interstitial fluid.<br>* Other names: RMM;Drug: Daily Methadone Dose<br>* patient takes their prescribed daily dose of methadone<br>* Other names: Dose Taken;|
| 3 Days<br>Microneedle electrode array placed into dermis for up to 3 days. DPV Scans performed at a frequency of 1-20 per hour. | Device: Remote Medication Monitor (RMM) - Prototype<br>* Inserted Microneedle Electrode Array for assaying dermal interstitial fluid.<br>* Other names: RMM;Drug: Daily Methadone Dose<br>* patient takes their prescribed daily dose of methadone<br>* Other names: Dose Taken;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of detection of methadone levels in Interstitial Fluid using an electrochemical sensor | Sensitivity of Repeated measurements of methadone levels | from 3 hours to 3 days. | 
| Specificity of detection of methadone levels in Interstitial Fluid using an electrochemical sensor | Specificity of Repeated measurements of methadone levels | from 3 hours to 3 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between Blood and ISF levels of Methadone and Methadone Metabolites assayed with Liquid Chromatography - Mass Spectroscopy (LC-MS) | Pearson coefficient | from 3 hours to 3 days | 
| Correlation between Blood and ISF levels of Methadone and Methadone Metabolites assayed with Remote Medication Monitor | Pearson coefficient | from 3 hours to 3 days | 
| Correlation between Liquid Chromatography - Mass Spectroscopy (LC-MS) and Differential Pulse Voltammetry (DPV) | Pearson Coefficient | from 3 hours to 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Differential Pulse Voltammetry, Remote Medication Monitor, Interstitial Fluid