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- Ensayo clínico NCT03525509
Epidural Methadone in Healthy Volunteers
Investigation of Pharmacokinetics and Pharmacodynamics of Epidural Methadone in Healthy Volunteers
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase temprana 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Missouri
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Saint Louis, Missouri, Estados Unidos, 63110
- Washington University in St. Louis
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Epidural methadone
A single 4mg epidural bolus of methadone hydrochloride
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Epidural bolus of 4mg of preservative free methadone hydrochloride (4mL of 1mg/mL solution)
Otros nombres:
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Comparador activo: Epidural morphine
A single 4mg epidural bolus of morphine sulfate
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Epidural bolus of 4mg of preservative free morphine sulfate (4mL of 1mg/mL solution)
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Selective segmental analgesia for heat pain - methadone
Periodo de tiempo: 0 -12 hours after medication administration
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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.
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0 -12 hours after medication administration
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Selective segmental analgesia for heat pain - morphine
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Simon Haroutounian, PhD, Washington University in Saint Louis
- Investigador principal: Yehuda Ginosar, MBBS, Washington University in Saint Louis
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Dolor
- Manifestaciones neurológicas
- Dolor agudo
- Efectos fisiológicos de las drogas
- Depresores del sistema nervioso central
- Agentes del sistema nervioso periférico
- Analgésicos
- Agentes del sistema sensorial
- Analgésicos Opiáceos
- Estupefacientes
- Agentes del sistema respiratorio
- Agentes antitusivos
- Morfina
- Metadona
Otros números de identificación del estudio
- 201802099
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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