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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Visit 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 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. |
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| Visit 3 | 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. |
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| Visit 1 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Measurement of Methadone in the Interstitial Fluid (ISF) before and after prescribed dose taken ex vivo | Diagnostic Test | Measurement of Methadone and its metabolites in interstitial fluid with Liquid Chromatography - Mass Spectroscopy (LC-MS) and Aptamer based Assay |
| Measure | Description | Time Frame |
|---|---|---|
| LC-MS based Proteome analysis of dermal interstitial fluid in non opioid use disordered patients | Measure the dermal interstitial fluid proteome using LC-MS in subjects without opioid use disorder | 1 day |
| 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 |
| Methadone Concentration in blood before and after a dose | measure blood for methadone with LC-MS before and after a daily dose | 1 day |
| 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 |
| 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 |
| Pearson Correlation of Methadone between ISF and Blood | measure blood and ISF methadone with LC-MS and determine pearson correlation | 2 days |
| Pearson Correlation between DPV and LC-MS ISF Methadone | measure ISF for methadone by LC-MS and DPV and determine Pearson correlation |
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Inclusion Criteria:
Exclusion Criteria:
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Chronic pain patients that have been prescribed at least 10mg of methadone per day.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Foster P Carr, MD | Contact | 6192343725 | drcarr@carihealth.com | |
| Torsten Feibig, PhD | Contact | torsten@carihealth.com |
| Name | Affiliation | Role |
|---|---|---|
| Charmaine Semenluk, MD | Synergy Research Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Synergy | Recruiting | Lemon Grove | California | 91945 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37395135 | Background | 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. | |
| 36642790 | Background | 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. |
| Label | URL |
|---|---|
| Cari Health Website | View source |
Not provided
| Type | Date | Date Unknown |
|---|---|---|
| Release | Feb 18, 2025 | |
| Reset | Mar 7, 2025 | |
| Release | Mar 7, 2025 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 14, 2023 | Aug 19, 2023 |
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interstitial fluid and fingerstick blood
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.
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| Measurement of Methadone in the Interstitial Fluid before and after prescribed dose taken in vivo | Drug | Measurement of Methadone and its metabolites in ISF with LC-MS and RMM |
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| ISF Extraction Device 2 | Device | Up to 15 minute periods of continuous ISF collection for analysis |
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| 2 days |
| Pearson Correlation between DPV and LC-MS ISF EDDP | measure ISF for EDDP by LC-MS and DPV and determine Pearson correlation | 2 days |
| Pearson Correlation between DPV and LC-MS blood EDDP | measure blood for EDDP by LC-MS and DPV and determine Pearson correlation | 2 days |
| 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 |
| 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 |
| EMDP concentration in ISF before and after daily dose of methadone | measure EMDP in ISF before and after daily dose of methadone | 1 day |
| 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 |
| 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 |
| 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 |
| 36748807 | Background | 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. |
| Kiffik Website | View source |
| Reset | Mar 28, 2025 |
| Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 1, 2024 | Aug 18, 2024 | ICF_002.pdf |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Feb 18, 2025 | Mar 7, 2025 | |||
| Mar 7, 2025 | Mar 28, 2025 |
| ID | Term |
|---|---|
| D059350 | Chronic Pain |
| C563835 | Drug Metabolism, Poor, CYP2D6-Related |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008691 | Methadone |
| ID | Term |
|---|---|
| D007659 | Ketones |
| D009930 | Organic Chemicals |
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