Assessment of Methadone and Buprenorphine in Interstitial Fluid

Opioid Use Disorder Clinical Trial

Official title:

Interstitial Fluid Collection Validation Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05546229
• Other study ID #: 1332356
• Secondary ID: 5R44DA044905-03
• Status: Completed
• Start date: September 14, 2022
• Est. completion date: October 31, 2022

Study information

• Verified date: June 2023
• Source: Cari Health Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: October 31, 2022
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Opioid Use Disorder
• Opioid-Related Disorders

Intervention

Procedure:
• Microneedle based interstitial fluid collection
Interstitial fluid will be collected from the skin using microneedles and suction.

Locations

Country	Name	City	State
United States	Synergy San Diego	Lemon Grove	California

Sponsors (3)

Lead Sponsor	Collaborator
Cari Health Inc.	National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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

External Links

•   Cari Health Inc.