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- Sperimentazione clinica NCT03525509
Epidural Methadone in Healthy Volunteers
Investigation of Pharmacokinetics and Pharmacodynamics of Epidural Methadone in Healthy Volunteers
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Prima fase 1
Contatti e Sedi
Luoghi di studio
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Missouri
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Saint Louis, Missouri, Stati Uniti, 63110
- Washington University in St. Louis
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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).
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: 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)
Altri nomi:
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Comparatore attivo: 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)
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Selective segmental analgesia for heat pain - methadone
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Selective segmental analgesia for heat pain - morphine
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Simon Haroutounian, PhD, Washington University in Saint Louis
- Investigatore principale: Yehuda Ginosar, MBBS, Washington University in Saint Louis
Pubblicazioni e link utili
Pubblicazioni generali
- 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.
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Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 201802099
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Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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