Assessment of Methadone and Buprenorphine in Interstitial Fluid

Interstitial Fluid Collection Validation Study

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

Study Overview

• Status: Completed
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Procedure: Microneedle based interstitial fluid collection

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 11

Contacts and Locations

Study Locations

• United States
  • California
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients receiving medication assisted treatment for opioid use disorder and control subjects not receiving any treatment for this condition.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls; Subjects not taking medications for opioid use disorder	Procedure: Microneedle based interstitial fluid collection; Interstitial fluid will be collected from the skin using microneedles and suction.
Methadone; Subjects taking methadone for opioid use disorder	Procedure: Microneedle based interstitial fluid collection; Interstitial fluid will be collected from the skin using microneedles and suction.
Buprenorphine; Subjects taking buprenorphine for opioid use disorder	Procedure: Microneedle based interstitial fluid collection; Interstitial fluid will be collected from the skin using microneedles and suction.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cari Health Inc.
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Mohammad Bari, MD, Synergy San Diego

Publications and helpful links

Helpful Links

• Cari Health Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2022
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: buprenorphine; methadone; interstitial fluid
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders
• Other Study ID Numbers: 1332356; 5R44DA044905-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No