Epidural Methadone in Healthy Volunteers

NCT03525509 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 201802099
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain, Acute

Keywords

Methadone; Morphine; Quantitative sensory testing; Epidural

Outcome Measures

Primary Outcomes (1)

• Selective segmental analgesia for heat pain - methadone

  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 Outcomes (3)

• Selective segmental analgesia for heat pain - morphine

  0 -12 hours after medication administration

• Selective segmental analgesia for pressure pain - methadone

  0 - 12 hours after medication administration

• Selective segmental analgesia for pressure pain - morphine

  0 - 12 hours after medication administration

Study Arms (2)

Epidural methadone

EXPERIMENTAL

A single 4mg epidural bolus of methadone hydrochloride

Drug: Methadone hydrochloride

Epidural morphine

ACTIVE COMPARATOR

A single 4mg epidural bolus of morphine sulfate

Drug: Morphine Sulfate

Interventions

Methadone hydrochloride DRUG

Epidural bolus of 4mg of preservative free methadone hydrochloride (4mL of 1mg/mL solution)

Also known as: Epidural methadone

Epidural methadone

Morphine Sulfate DRUG

Epidural bolus of 4mg of preservative free morphine sulfate (4mL of 1mg/mL solution)

Also known as: Epidural morphine

Epidural morphine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• simon.haroutounian: lead

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• Shir Y, Rosen G, Zeldin A, Davidson EM. Methadone is safe for treating hospitalized patients with severe pain. Can J Anaesth. 2001 Dec;48(11):1109-13. doi: 10.1007/BF03020377.

  PMID: 11744587 BACKGROUND

• Haroutiunian S, Kagan L, Yifrach-Damari I, Davidson E, Ratz Y, Hoffman A. Enhanced antinociceptive efficacy of epidural compared with i.v. methadone in a rat model of thermal nociception. Br J Anaesth. 2014 Jan;112(1):150-8. doi: 10.1093/bja/aet234. Epub 2013 Jul 10.

  PMID: 23842610 BACKGROUND

• Bernards CM, Shen DD, Sterling ES, Adkins JE, Risler L, Phillips B, Ummenhofer W. Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 1): differences among opioids. Anesthesiology. 2003 Aug;99(2):455-65. doi: 10.1097/00000542-200308000-00029.

  PMID: 12883420 BACKGROUND

• Gedney JA, Liu EH. Side-effects of epidural infusions of opioid bupivacaine mixtures. Anaesthesia. 1998 Dec;53(12):1148-55. doi: 10.1046/j.1365-2044.1998.00636.x.

  PMID: 10193215 BACKGROUND

MeSH Terms

Conditions

Acute Pain

Interventions

Methadone; Morphine

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Simon Haroutounian, PhD

  Washington University in Saint Louis

  PRINCIPAL INVESTIGATOR

• Yehuda Ginosar, MBBS

  Washington University in Saint Louis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: At enrollment, each participant will be assigned a study number, which will match a previously prepared computer-generated list of randomization numbers to determine the interventions. Pharmacy staff who prepares blinded syringes of medications for administration will not be involved in medication administration, outcomes assessment, or statistical analysis. The participants and all other study personnel will be blinded to the treatment allocation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology, Chief of Clinical Research for Washington University Pain Center

Model Details: Randomized, double-blinded, crossover design in healthy volunteers

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: May 15, 2018
• Study Start: June 4, 2018
• Primary Completion: August 28, 2019
• Study Completion: August 30, 2019
• Last Updated: September 18, 2019

Record last verified: 2019-09

Locations

US (1)