Assessment of Methadone Dose Taken Using Electrochemistry

Conditions: Methadone Overdose
Drug Metabolism, Poor, CYP2D6-Related
Methadone Toxicity
Pain, Chronic
Metabolism Medication Toxicity

Interventions: Device: ISF extraction device 1
Diagnostic Test: Measurement of Methadone in the Interstitial Fluid (ISF) before and after prescribed dose taken ex vivo
Device: Measurement of Methadone in the Interstitial Fluid before and after prescribed dose taken in vivo
Drug: Measurement of Methadone in ISF before and after taking prescribed dose
Device: ISF Extraction Device 2

Registration Number: NCT05981573

Lead Sponsor: Cari Health Inc.

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 Differential Pulse Voltammetry (DPV).

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. The electronics for the RMM prototypes will consist of commercially available benchtop potentiostats like the PalmSens Sensit BT (https://www.palmsens.com/product/palmsens4/) or CH Instruments 660D (https://www.chinstruments.com/) and will not be in direct contact with the 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.

Recruitment & Eligibility

Status: ENROLLING_BY_INVITATION

Sex: All

Target Recruitment: 30

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.

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Visit 2	ISF Extraction Device 2	AIM 2 : Determine if an RMM can assess the status of taking a prescribed dose of methadone. To complete this aim, the peak and trough concentrations of a witnessed methadone dose will be assessed in ISF collected through the surface of the skin using existing ISF extraction methods and assessed outside the body via differential pulse voltammetry (DPV) for up to 6 hours. Methadone metabolites and protein binding factors may be assessed in the collected ISF samples using (LC-MS). We hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF. The Investigators hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF.
Visit 3	ISF extraction device 1	AIM 3: Determine if an RMM can continuously assess the status of taking a prescribed dose of methadone over time. To complete this aim, the pharmacokinetic profile of a witnessed methadone dose will be assessed in ISF continuously from the surface of the skin using the RMM for up to 12 hours (Aim 3a) and over 3 days (Aim 3b). Methadone metabolites will also be assessed over these three time points in the continuously collected ISF samples using LC-MS. The Investigators hypothesize that a clinician can recognize a dose taken and the methadone metabolites from the RMM generated measurements in the ISF.
Visit 3	Measurement of Methadone in the Interstitial Fluid (ISF) before and after prescribed dose taken ex vivo	AIM 3: Determine if an RMM can continuously assess the status of taking a prescribed dose of methadone over time. To complete this aim, the pharmacokinetic profile of a witnessed methadone dose will be assessed in ISF continuously from the surface of the skin using the RMM for up to 12 hours (Aim 3a) and over 3 days (Aim 3b). Methadone metabolites will also be assessed over these three time points in the continuously collected ISF samples using LC-MS. The Investigators hypothesize that a clinician can recognize a dose taken and the methadone metabolites from the RMM generated measurements in the ISF.
Visit 2	Measurement of Methadone in the Interstitial Fluid before and after prescribed dose taken in vivo	AIM 2 : Determine if an RMM can assess the status of taking a prescribed dose of methadone. To complete this aim, the peak and trough concentrations of a witnessed methadone dose will be assessed in ISF collected through the surface of the skin using existing ISF extraction methods and assessed outside the body via differential pulse voltammetry (DPV) for up to 6 hours. Methadone metabolites and protein binding factors may be assessed in the collected ISF samples using (LC-MS). We hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF. The Investigators hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF.
Visit 3	ISF Extraction Device 2	AIM 3: Determine if an RMM can continuously assess the status of taking a prescribed dose of methadone over time. To complete this aim, the pharmacokinetic profile of a witnessed methadone dose will be assessed in ISF continuously from the surface of the skin using the RMM for up to 12 hours (Aim 3a) and over 3 days (Aim 3b). Methadone metabolites will also be assessed over these three time points in the continuously collected ISF samples using LC-MS. The Investigators hypothesize that a clinician can recognize a dose taken and the methadone metabolites from the RMM generated measurements in the ISF.
Visit 1	ISF Extraction Device 2	Aim 1: Characterize dermal interstitial fluid (ISF) in healthy adults with Liquid Chromatography-Mass Spectroscopy (LC-MS) based proteomics and Differential Pulse Voltammetry. To complete this aim, the dermal interstitial fluid will be extracted from the surface of the skin of healthy adults over a period up to 3 hours. The participants may also have continuous monitoring of their intradermal differential pulse voltammogram using the RMM. We hypothesize that the protein content of ISF will be 50% the level of normal human serum levels and contain potential protein biomarkers of disease status. We also hypothesize that the baseline DPV will be stable over this time period.
Visit 2	ISF extraction device 1	AIM 2 : Determine if an RMM can assess the status of taking a prescribed dose of methadone. To complete this aim, the peak and trough concentrations of a witnessed methadone dose will be assessed in ISF collected through the surface of the skin using existing ISF extraction methods and assessed outside the body via differential pulse voltammetry (DPV) for up to 6 hours. Methadone metabolites and protein binding factors may be assessed in the collected ISF samples using (LC-MS). We hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF. The Investigators hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF.
Visit 2	Measurement of Methadone in the Interstitial Fluid (ISF) before and after prescribed dose taken ex vivo	AIM 2 : Determine if an RMM can assess the status of taking a prescribed dose of methadone. To complete this aim, the peak and trough concentrations of a witnessed methadone dose will be assessed in ISF collected through the surface of the skin using existing ISF extraction methods and assessed outside the body via differential pulse voltammetry (DPV) for up to 6 hours. Methadone metabolites and protein binding factors may be assessed in the collected ISF samples using (LC-MS). We hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF. The Investigators hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF.
Visit 2	Measurement of Methadone in ISF before and after taking prescribed dose	AIM 2 : Determine if an RMM can assess the status of taking a prescribed dose of methadone. To complete this aim, the peak and trough concentrations of a witnessed methadone dose will be assessed in ISF collected through the surface of the skin using existing ISF extraction methods and assessed outside the body via differential pulse voltammetry (DPV) for up to 6 hours. Methadone metabolites and protein binding factors may be assessed in the collected ISF samples using (LC-MS). We hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF. The Investigators hypothesize that the methadone peak and trough levels as well as the metabolites in the blood samples will correlate with the levels of methadone in ISF.
Visit 3	Measurement of Methadone in ISF before and after taking prescribed dose	AIM 3: Determine if an RMM can continuously assess the status of taking a prescribed dose of methadone over time. To complete this aim, the pharmacokinetic profile of a witnessed methadone dose will be assessed in ISF continuously from the surface of the skin using the RMM for up to 12 hours (Aim 3a) and over 3 days (Aim 3b). Methadone metabolites will also be assessed over these three time points in the continuously collected ISF samples using LC-MS. The Investigators hypothesize that a clinician can recognize a dose taken and the methadone metabolites from the RMM generated measurements in the ISF.
Visit 3	Measurement of Methadone in the Interstitial Fluid before and after prescribed dose taken in vivo	AIM 3: Determine if an RMM can continuously assess the status of taking a prescribed dose of methadone over time. To complete this aim, the pharmacokinetic profile of a witnessed methadone dose will be assessed in ISF continuously from the surface of the skin using the RMM for up to 12 hours (Aim 3a) and over 3 days (Aim 3b). Methadone metabolites will also be assessed over these three time points in the continuously collected ISF samples using LC-MS. The Investigators hypothesize that a clinician can recognize a dose taken and the methadone metabolites from the RMM generated measurements in the ISF.

Primary Outcome Measures

Name	Time	Method
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 blood before and after a dose	1 day	measure blood for methadone with LC-MS before and after a daily dose
Pearson Correlation between DPV and LC-MS ISF EDDP	2 days	measure ISF for EDDP by LC-MS and DPV and determine Pearson correlation
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
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.
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
Pearson Correlation of Methadone between ISF and Blood	2 days	measure blood and ISF methadone with LC-MS and determine pearson correlation
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
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 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 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
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 DPV	2 days	Calculate methadone to EDDP ratio of ISF and Blood and determine Pearson Correlation using DPV

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (1): Synergy
🇺🇸
Lemon Grove, California, United States

Assessment of Methadone Dose Taken Using Electrochemistry

Recruitment & Eligibility

Study & Design

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