Drug Metabolism, Poor, CYP2D6-Related, Metabolism Medication Toxicity, Methadone Overdose, Methadone Toxicity, Pain, Chronic
Conditions
Keywords
Pharmacokinetics
Brief summary
Proof of concept: Pilot Study A Pilot, proof of concept, observational study with a long-term goal to develop a minimally invasive wearable Remote Medication Monitor (RMM) that provides continuous, real-time data on methadone levels in interstitial fluid (ISF). An RMM could be used as a medication adherence monitor and would allow for the physician, counselor, patient, or family member to remotely verify that a physician-prescribed dose has been taken.
Detailed description
The investigator will conduct a non-randomized, non-blinded, feasibility study at a single center in the United States. The study will include up to 20 subjects of an equal number of male and female adults (ages 18-70) who have a prescription for methadone for chronic pain. In Aim 1, the investigator will determine if an RMM can assess the status of taking a prescribed dose of methadone, using biosamples (i.e., ISF, blood) collected from subjects and tested in a laboratory setup. Biosample collections and pharmacokinetic monitoring will take up to 6 consecutive hours. By completing this aim, the investigator will determine if a physician is able to recognize the peak and trough of a methadone dose using ex vivo Continuous Monitor. In Aim 2, the investigator will determine if an RMM can continuously assess the status of taking a prescribed dose of methadone over time, by inserting the intradermal microneedle sensing elements into the subjects' skin. Biosample collections (i.e., ISF, blood) and pharmacokinetic monitoring will occur over a 6-hour period. By completing this aim, the investigator will determine if a physician is able to recognize the pharmacokinetic profile of a taken dose of methadone. The physician will see a dosing curve display generated from intradermal microneedle sensing elements that are worn continuously on the skin. Completion of Aims 1-2 will require two separate visits.
Interventions
DIAGNOSTIC_TESTMeasurement of Methadone in the Interstitial Fluid (ISF) before and after prescribed dose taken ex vivo
Measurement of Methadone and its metabolites in interstitial fluid with Liquid Chromatography - Mass Spectroscopy (LC-MS) and Aptamer based Assay
DRUGMeasurement of Methadone in the Interstitial Fluid before and after prescribed dose taken in vivo
Measurement of Methadone and its metabolites in ISF with LC-MS and RMM
DEVICEISF Extraction Device 2
Up to 15 minute periods of continuous ISF collection for analysis
Sponsors
Cari Health Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-70 * A prescription for methadone for chronic pain at a dose of 10mg or more for at least one week. * Taking methadone as prescribed during the last 4 days before consent to participate in the study.
Exclusion criteria
* Age \<18 or \>70 * A condition preventing or complicating ISF collection * dermatological (skin) condition * immunodeficiency * recent blood donation * anemia * end stage renal disease * liver cirrhosis * cancer * congestive heart failure * bleeding diathesis * tuberculosis (TB) * Any active severe depression * suicidal ideation * mania symptoms * Pregnancy * Intending to become pregnant during the course of the study * Enrolled in a substance use disorder treatment program * Under a conservatorship.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LC-MS based Proteome analysis of dermal interstitial fluid in non opioid use disordered patients | 1 day | Measure the dermal interstitial fluid proteome using LC-MS in subjects without opioid use disorder |
| Methadone Concentration in ISF before and after a dose | 1 day | measure dermal interstitial fluid with LC-MS for methadone before and after a daily dose |
| Methadone Concentration in blood before and after a dose | 1 day | measure blood for methadone with LC-MS before and after a daily dose |
| Concentration of Methadone in ISF with LC-MS versus Electrochemical Assay | 2 days | measure ISF with two procedures (Liquid Chromatography - Mass Spectroscopy and Differential Pulse Voltammetry. |
| Concentration of Methadone in blood with LC-MS versus Electrochemical Assay | 2 days | measure blood with two procedures (Liquid Chromatography - Mass Spectroscopy and Differential Pulse Voltammetry. |
| Pearson Correlation of Methadone between ISF and Blood | 2 days | measure blood and ISF methadone with LC-MS and determine pearson correlation |
| Pearson Correlation between DPV and LC-MS ISF Methadone | 2 days | measure ISF for methadone by LC-MS and DPV and determine Pearson correlation |
| Pearson Correlation between DPV and LC-MS ISF EDDP | 2 days | measure ISF for EDDP by LC-MS and DPV and determine Pearson correlation |
| Pearson Correlation between DPV and LC-MS blood EDDP | 2 days | measure blood for EDDP by LC-MS and DPV and determine Pearson correlation |
| EDDP concentration in ISF before and after daily dose of methadone | 1 day | measure ISF for EDDP by LC-MS before and after daily dose of methadone |
| EDDP concentration in blood before and after daily dose of methadone | 1 day | measure blood for EDDP by LC-MS before and after daily dose of methadone |
| EMDP concentration in ISF before and after daily dose of methadone | 1 day | measure EMDP in ISF before and after daily dose of methadone |
| EMDP concentration in blood before and after daily dose of methadone | 1 day | measure EMDP in blood by LC-MS before and after daily dose of methadone |
| Pearson Correlation of Methadone to Metabolite Ratio ( MMR ) between ISF and Blood using LC-MS | 2 days | Calculate methadone to EDDP ratio of ISF and Blood and determine Pearson Correlation using LC-MS |
| Pearson Correlation of Methadone to Metabolite Ratio ( MMR ) between ISF and Blood using DPV | 2 days | Calculate methadone to EDDP ratio of ISF and Blood and determine Pearson Correlation using DPV |
Countries
United States
Contacts
Primary ContactFoster P Carr, MD
Backup ContactTorsten Feibig, PhD
Outcome results
None listed