Assessment of Methadone and Buprenorphine in Interstitial Fluid

Study Overview
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Brief Summary
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The purpose of this research is to determine if common medications for opioid use disorder (i.e., buprenorphine/naloxone, buprenorphine, methadone) and their metabolites (norbuprenorphine [a metabolite of buprenorphine], buprenorphine-3-glucuronide [B3G; a metabolite in buprenorphine], ethylidene dimethyl diphenyl pyrrolidine [EDDP; a metabolite of methadone]) can be detected in the dermal interstitial fluid (i.e., fluid extracted from the surface of the skin). Additional subjects who are not prescribed or taking any of these medications will be included in this study to act as a comparison group

Detailed Description
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This pilot study is an exploratory feasibility study that aims to determine if common medications for opioid use disorder (OUD; i.e., buprenorphine, methadone) and their metabolites (i.e., norbuprenorphine [a metabolite of buprenorphine], buprenorphine-3-glucuronide [B3G; a metabolite in buprenorphine], ethylidene dimethyl diphenyl pyrrolidine [EDDP; a metabolite for methadone]), can be detected in dermal interstitial fluid (ISF). Microliter volumes of ISF from the surface of the skin will be collected from patients with a prescription for each these medications (buprenorphine n = 10; methadone n = 10) and controls (n=2) using a microneedle patch or minimally invasive microneedle array that may be used in conjunction with a standard vacuum pump. Levels of these medications and their metabolites will then be detected and quantitated in these samples using standard and well-established instrumental analysis for comparison to blood samples. Aim 1: Detect and quantitate buprenorphine and norbuprenorphine in ISF collected from the surface of the skin using a minimally invasive microneedle array. ISF collected from the surface of the skin will be tested for buprenorphine (i.e., Suboxone®, Subutex®), norbuprenorphine (a metabolite of buprenorphine), and B3G (a metabolite of buprenorphine) using standard instrumental analysis. Aim 2: Detect and quantitate methadone in ISF collected from the surface of the skin using a minimally invasive microneedle array. ISF collected from the surface of the skin will be tested for methadone and EDDP using standard instrumental analysis. Aim 3: Establish correspondence between detected medication levels in ISF and blood. Medication levels for buprenorphine and methadone detected in the ISF will be compared to medication levels measured in blood samples for the purpose of understanding the correlation between the ISF and blood levels.

Official Title
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Interstitial Fluid Collection Validation Study

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Procedure: Microneedle based interstitial fluid collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65. A prescription for buprenorphine at dose ≥ 16 mg/4mg, a prescription for buprenorphine/naloxone at dose ≥ 16 mg/4mg, a prescription for methadone at dose ≥ 60mg, or part of the control group. Taken buprenorphine, buprenorphine/naloxone, or methadone as prescribed in the last 7 days, or part of the control group Exclusion Criteria: A condition preventing or complicating ISF collection. Conditions may include dermatological (skin) condition, immunodeficiency, recent blood donation, anemia, cancer, congestive heart failure, HIV, Hepatitis C [HCV], or tuberculosis [TB]. Any active severe depression (e.g., suicidal ideation) or mania symptoms. Lactation, pregnancy, or intending to become pregnant during the course of the study. Alcohol use in the past 7 days. Illicit substance use in past 7 days (e.g., heroin, methamphetamines). Under a conservatorship.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Controls<br>Subjects not taking medications for opioid use disorder | Procedure: Microneedle based interstitial fluid collection<br>* Interstitial fluid will be collected from the skin using microneedles and suction.<br>|
| Methadone<br>Subjects taking methadone for opioid use disorder | Procedure: Microneedle based interstitial fluid collection<br>* Interstitial fluid will be collected from the skin using microneedles and suction.<br>|
| Buprenorphine<br>Subjects taking buprenorphine for opioid use disorder | Procedure: Microneedle based interstitial fluid collection<br>* Interstitial fluid will be collected from the skin using microneedles and suction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methadone Concentration in Plasma and Interstitial Fluid (ISF) Before and After Taking a Dose | ISF collected from the surface of the skin along with blood plasma by venipuncture will be tested for methadone using LC-MS analysis. | 1 day | 
| Methadone Metabolite/ 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine ( EDDP ) Concentration in ISF and Plasma Before and After Taking a Dose of Methadone | Plasma and ISF collected from the surface of the skin will be tested for methadone metabolite /eddp using LC-MS analysis. Detection will be performed before and 3 hours after taking prescribed dose of methadone. | 1 day | 
| Methadone and Its Metabolite/ EDDP Concentrations Using Liquid Chromatography Mass Spectroscopy (LC-MS) in Subjects Not Taking Methadone | Plasma collected from subjects not taking methadone by venipuncture and ISF collected from the surface of the skin. Samples tested for methadone and methadone metabolite /eddp using Liquid Chromatography-Mass Spec (LC-MS) analysis . | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pearson Correlation for Methadone Levels in ISF and Blood | The Pearson correlation coefficient of blood and ISF methadone levels was calculated using the Least Squared Method from Microsoft Excel software. | 1 day | 
| Pearson Correlation Coefficient for Methadone Metabolite / EDDP Levels in ISF and Blood | The Pearson correlation coefficient between the ISF and blood levels of EDDP were calculated using the Least Squared Method by Microsoft Excel software. | 1 day | 
| Buprenorphine Concentration in Plasma and ISF Before and After a Dose Taken | Plasma collected by venipuncture and ISF collected from the surface of the skin will be tested for buprenorphine using LC-MS analysis before and after a dose of buprenorphine has been taken | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methadone, buprenorphine, interstitial fluid