Clinical trial NCT05981573: Assessment of Methadone Dose Taken
Official title: Assessment of Methadone Dose Taken
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Methadone Toxicity
Methadone Overdose
Pain, Chronic
Drug Metabolism, Poor, CYP2D6-Related
Metabolism Medication Toxicity
Keywords: Pharmacokinetics
Lead sponsor: Cari Health Inc.
Sponsor class: OTHER
First posted: 2023-08-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chronic pain patients that have been prescribed at least 10mg of methadone per day.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: LC-MS based Proteome analysis of dermal interstitial fluid in non opioid use disordered patients
timeFrame: 1 day
measure: Methadone Concentration in ISF before and after a dose
timeFrame: 1 day
measure: Methadone Concentration in blood before and after a dose
timeFrame: 1 day
measure: Concentration of Methadone in ISF with LC-MS versus Electrochemical Assay
timeFrame: 2 days
measure: Concentration of Methadone in blood with LC-MS versus Electrochemical Assay
timeFrame: 2 days
measure: Pearson Correlation of Methadone between ISF and Blood
timeFrame: 2 days
measure: Pearson Correlation between DPV and LC-MS ISF Methadone
timeFrame: 2 days
measure: Pearson Correlation between DPV and LC-MS ISF EDDP
timeFrame: 2 days
measure: Pearson Correlation between DPV and LC-MS blood EDDP
timeFrame: 2 days
measure: EDDP concentration in ISF before and after daily dose of methadone
timeFrame: 1 day
measure: EDDP concentration in blood before and after daily dose of methadone
timeFrame: 1 day
measure: EMDP concentration in ISF before and after daily dose of methadone
timeFrame: 1 day
measure: EMDP concentration in blood before and after daily dose of methadone
timeFrame: 1 day
measure: Pearson Correlation of Methadone to Metabolite Ratio ( MMR ) between ISF and Blood using LC-MS
timeFrame: 2 days
measure: Pearson Correlation of Methadone to Metabolite Ratio ( MMR ) between ISF and Blood using DPV
timeFrame: 2 days
Secondary outcomes:
Other outcomes:
Locations:
city: Lemon Grove
country: United States
facility: Synergy
state: California
Study officials:
affiliation: Synergy Research Inc.
name: Charmaine Semenluk, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.