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Epidural Methadone in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03525509
Recruitment Status : Completed
First Posted : May 15, 2018
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
simon.haroutounian, Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE May 2, 2018
First Posted Date  ICMJE May 15, 2018
Last Update Posted Date September 18, 2019
Actual Study Start Date  ICMJE June 4, 2018
Actual Primary Completion Date August 28, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2018)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Epidural Methadone in Healthy Volunteers
Official Title  ICMJE Investigation of Pharmacokinetics and Pharmacodynamics of Epidural Methadone in Healthy Volunteers
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.
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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Randomized, double-blinded, crossover design in healthy volunteers
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Treatment
Condition  ICMJE Pain, Acute
Intervention  ICMJE
  • Drug: Methadone hydrochloride
    Epidural bolus of 4mg of preservative free methadone hydrochloride (4mL of 1mg/mL solution)
    Other Name: Epidural methadone
  • Drug: Morphine Sulfate
    Epidural bolus of 4mg of preservative free morphine sulfate (4mL of 1mg/mL solution)
    Other Name: Epidural morphine
Study Arms  ICMJE
  • Experimental: Epidural methadone
    A single 4mg epidural bolus of methadone hydrochloride
    Intervention: Drug: Methadone hydrochloride
  • Active Comparator: Epidural morphine
    A single 4mg epidural bolus of morphine sulfate
    Intervention: Drug: Morphine Sulfate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 14, 2018)
13
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 30, 2019
Actual Primary Completion Date August 28, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03525509
Other Study ID Numbers  ICMJE 201802099
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party simon.haroutounian, Washington University School of Medicine
Study Sponsor  ICMJE simon.haroutounian
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Simon Haroutounian, PhD Washington University in Saint Louis
Principal Investigator: Yehuda Ginosar, MBBS Washington University in Saint Louis
PRS Account Washington University School of Medicine
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP