Assessment of Methadone Dose Taken Using Electrochemistry

Pain, Chronic Clinical Trial

Official title:

Assessment of Methadone Dose Taken Using Electrochemistry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05981573
• Other study ID #: 1358643
• Status: Recruiting
• Start date: June 2024
• Est. completion date: September 2024

Study information

• Verified date: February 2024
• Source: Cari Health Inc.
• Contact: Foster P Carr, MD
• Phone: 6192343725
• Email: drcarr[@]carihealth.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Pain
• Drug Metabolism, Poor, CYP2D6-Related
• Metabolism Medication Toxicity
• Methadone Toxicity
• Pain, Chronic

Intervention

Device:
• ISF extraction device 1
FDA approved microneedle attached to blotter paper tested for ability to extract 1ul of interstitial fluid

Diagnostic Test:
• Measurement 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 Electrochemical Assay

Device:
• Measurement 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 DPV

Drug:
• Measurement of Methadone in ISF before and after taking prescribed dose
Measurement of methadone in ISF using DPV ex vivo versus in vivo . (Accuracy comparison - sensitivity, specificity, level of detection, and standard deviations )

Device:
• ISF Extraction Device 2
2 hour periods of continuous ISF collection for analysis

Locations

Country	Name	City	State
United States	Synergy	Lemon Grove	California

Sponsors (1)

Lead Sponsor	Collaborator
Cari Health Inc.

Country where clinical trial is conducted

United States, 

References & Publications (3)

Friedel M, Werbovetz B, Drexelius A, Watkins Z, Bali A, Plaxco KW, Heikenfeld J. Continuous molecular monitoring of human dermal interstitial fluid with microneedle-enabled electrochemical aptamer sensors. Lab Chip. 2023 Jul 12;23(14):3289-3299. doi: 10.1039/d3lc00210a. — View Citation

Gomes NO, Raymundo-Pereira PA. On-Site Therapeutic Drug Monitoring of Paracetamol Analgesic in Non-Invasively Collected Saliva for Personalized Medicine. Small. 2023 Mar;19(12):e2206753. doi: 10.1002/smll.202206753. Epub 2023 Jan 15. — View Citation

Ribet F, Bendes A, Fredolini C, Dobielewski M, Bottcher M, Beck O, Schwenk JM, Stemme G, Roxhed N. Microneedle Patch for Painless Intradermal Collection of Interstitial Fluid Enabling Multianalyte Measurement of Small Molecules, SARS-CoV-2 Antibodies, and Protein Profiling. Adv Healthc Mater. 2023 May;12(13):e2202564. doi: 10.1002/adhm.202202564. Epub 2023 Feb 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Methadone Concentration in ISF before and after a dose	measure dermal interstitial fluid with LC-MS for methadone before and after a daily dose	1 day
Primary	Methadone Concentration in blood before and after a dose	measure blood for methadone with LC-MS before and after a daily dose	1 day
Primary	Concentration of Methadone in ISF with LC-MS versus Electrochemical Assay	measure ISF with two procedures (Liquid Chromatography - Mass Spectroscopy and Differential Pulse Voltammetry.	2 days
Primary	Concentration of Methadone in blood with LC-MS versus Electrochemical Assay	measure blood with two procedures (Liquid Chromatography - Mass Spectroscopy and Differential Pulse Voltammetry.	2 days
Primary	Pearson Correlation of Methadone between ISF and Blood	measure blood and ISF methadone with LC-MS and determine pearson correlation	2 days
Primary	Pearson Correlation between DPV and LC-MS ISF Methadone	measure ISF for methadone by LC-MS and DPV and determine Pearson correlation	2 days
Primary	Pearson Correlation between DPV and LC-MS ISF EDDP	measure ISF for EDDP by LC-MS and DPV and determine Pearson correlation	2 days
Primary	Pearson Correlation between DPV and LC-MS blood EDDP	measure blood for EDDP by LC-MS and DPV and determine Pearson correlation	2 days
Primary	EDDP concentration in ISF before and after daily dose of methadone	measure ISF for EDDP by LC-MS before and after daily dose of methadone	1 day
Primary	EDDP concentration in blood before and after daily dose of methadone	measure blood for EDDP by LC-MS before and after daily dose of methadone	1 day
Primary	EMDP concentration in ISF before and after daily dose of methadone	measure EMDP in ISF before and after daily dose of methadone	1 day
Primary	EMDP concentration in blood before and after daily dose of methadone	measure EMDP in blood by LC-MS before and after daily dose of methadone	1 day
Primary	Pearson Correlation of Methadone to Metabolite Ratio ( MMR ) between ISF and Blood using LC-MS	Calculate methadone to EDDP ratio of ISF and Blood and determine Pearson Correlation using LC-MS	2 days
Primary	Pearson Correlation of Methadone to Metabolite Ratio ( MMR ) between ISF and Blood using DPV	Calculate methadone to EDDP ratio of ISF and Blood and determine Pearson Correlation using DPV	2 days

External Links

•   Cari Health Website
•   Kiffik Website