Epidural Methadone in Healthy Volunteers

September 17, 2019 updated by: simon.haroutounian

Investigation of Pharmacokinetics and Pharmacodynamics of Epidural Methadone in Healthy Volunteers

Epidurally administered opioid pain medications are important tools for postoperative pain control, but each agent has its own limitations. Methadone's properties suggest that it may provide a long duration of pain control with minimal side effects related to spread to the brain or absorption into the blood stream. In this study, the investigators aim to compare the relative pain relieving effects, markers of side effects, and concentrations in the blood of epidurally administered methadone as compared to another long-acting opioid which is commonly administered epidurally, morphine.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acute postoperative pain control remains a major challenge in healthcare, with a need to balance analgesic effectiveness, patient safety, and cost. Excellent analgesia is a universal clinical imperative, but our current approaches are often inadequate. Epidural opioids can be useful tools, but each carries its own strengths and limitations. Bolus morphine is long lasting but exhibits rostral spread in the cerebrospinal fluid, which raises risks of adverse effects, particularly late-onset respiratory depression. Lipophilic opioids such as fentanyl and sufentanil exhibit selective segmental analgesia but are of short duration due to systemic absorption. As such, they require continuous epidural administration via an indwelling epidural catheter and a pump (patient-controlled or continuous infusion), which has implications for nursing, pain management services, and hospital cost. Methadone's physico-chemical properties suggest that epidural methadone administration would be ideal in providing long-duration analgesia with fewer of the adverse effects seen with medications like morphine.

The aim of this study is to compare the effects of two medications given epidurally: morphine and methadone. We will do so using a randomized, double-blinded, crossover design study. During each of two study visits, participants will receive a single epidural bolus of either morphine or methadone. We will examine the ability of the medication to blunt pain from heat or pressure using quantitative sensory testing at both the dermatome of injection (leg) and a distant dermatome (face); in doing so, we will demonstrate relative segmental versus supraspinal or systemic opioid activity. Additionally, we will assess signs and symptoms of supraspinal opioid activity, which may predispose to adverse effects, and blood concentrations of each medication. Each of the aforementioned measurements will be conducted at multiple points over a 24 hour period. Following a washout period, patients will return for a second visit, at which time the protocol will be repeated using the other medication.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University in St. Louis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥18;
  2. Body mass index between 18.5 and 30
  3. Good general health with no remarkable medical conditions;
  4. Able and willing to provide informed consent.

Exclusion Criteria:

  1. Known history of hepatic, renal, and cardiac disease;
  2. Known history of diabetes mellitus;
  3. Chronic pain;
  4. A skin or spine condition preventing safe epidural catheter placement;
  5. Current pregnancy or lactation;
  6. Known coagulopathy or ongoing anticoagulant use which contraindicates epidural catheter placement;
  7. Known allergic reactions to opioids or local anesthetics;
  8. History of current or prior substance use disorder or positive screen using the 4-question Simple Screening Instrument for Substance Abuse (SSI-SA).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Epidural methadone
A single 4mg epidural bolus of methadone hydrochloride
Drug: Methadone hydrochloride
Epidural bolus of 4mg of preservative free methadone hydrochloride (4mL of 1mg/mL solution)
Other Names:
  • Epidural methadone
Active Comparator: Epidural morphine
A single 4mg epidural bolus of morphine sulfate
Drug: Morphine Sulfate
Epidural bolus of 4mg of preservative free morphine sulfate (4mL of 1mg/mL solution)
Other Names:
  • Epidural morphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Selective segmental analgesia for heat pain - methadone
Time Frame: 0 -12 hours after medication administration
The analgesia provided by methadone at a given dermatome will be quantified as the area under the curve (AUC) of the heat pain tolerance threshold versus time curve. The selective segmental analgesic effect of methadone will be measured as difference of the AUC for L3 and V2.
0 -12 hours after medication administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Selective segmental analgesia for heat pain - morphine
Time Frame: 0 -12 hours after medication administration
The analgesia provided by morphine at a given dermatome will be quantified as the area under the curve (AUC) of the heat pain tolerance threshold versus time curve. The selective segmental analgesic effect of morphine will be measured as difference of the AUC for L3 and V2.
0 -12 hours after medication administration
Selective segmental analgesia for pressure pain - methadone
Time Frame: 0 - 12 hours after medication administration
The analgesia provided by methadone at a given dermatome will be quantified as the area under the curve (AUC) of the pressure pain threshold versus time curve. The selective segmental analgesic effect of methadone will be measured as difference of the AUC for L3 and V2.
0 - 12 hours after medication administration
Selective segmental analgesia for pressure pain - morphine
Time Frame: 0 - 12 hours after medication administration
The analgesia provided by morphine at a given dermatome will be quantified as the area under the curve (AUC) of the pressure pain threshold versus time curve. The selective segmental analgesic effect of morphine will be measured as difference of the AUC for L3 and V2.
0 - 12 hours after medication administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

simon.haroutounian

Investigators

  • Principal Investigator: Simon Haroutounian, PhD, Washington University in Saint Louis
  • Principal Investigator: Yehuda Ginosar, MBBS, Washington University in Saint Louis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 4, 2018

Primary Completion (Actual)

August 28, 2019

Study Completion (Actual)

August 30, 2019

Study Registration Dates

First Submitted

May 2, 2018

First Submitted That Met QC Criteria

May 14, 2018

First Posted (Actual)

May 15, 2018

Study Record Updates

Last Update Posted (Actual)

September 18, 2019

Last Update Submitted That Met QC Criteria

September 17, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201802099

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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