Assessment of Methadone Dose Taken

CARI Health

Status: Enrolling

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

Treatments: Device: ISF Extraction Device 2; Drug: Measurement of Methadone in the Interstitial Fluid before and after prescribed dose taken in vivo; Diagnostic Test: Measurement of Methadone in the Interstitial Fluid (ISF) before and after prescribed dose taken ex vivo

Study type: Observational

Funder types: Other

Identifiers

NCT05981573

1358643

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

30 participants in 3 patient groups

Visit 2

Description:

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 Lateral Flow Immunoassay 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.

Treatment:

Diagnostic Test: Measurement of Methadone in the Interstitial Fluid (ISF) before and after prescribed dose taken ex vivo

Drug: Measurement of Methadone in the Interstitial Fluid before and after prescribed dose taken in vivo

Device: ISF Extraction Device 2

Visit 3

Description:

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.

Treatment:

Diagnostic Test: Measurement of Methadone in the Interstitial Fluid (ISF) before and after prescribed dose taken ex vivo

Drug: Measurement of Methadone in the Interstitial Fluid before and after prescribed dose taken in vivo

Device: ISF Extraction Device 2

Visit 1

Description:

Aim 1: Characterize dermal interstitial fluid (ISF) in healthy adults with Liquid Chromatography-Mass Spectroscopy (LC-MS) based proteomics. 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 interstitial fluid 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.

Treatment:

Device: ISF Extraction Device 2