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Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume

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ClinicalTrials.gov Identifier: NCT03283020
Recruitment Status : Unknown
Verified December 2017 by Johanna Savilampi, Region Örebro County.
Recruitment status was:  Recruiting
First Posted : September 14, 2017
Last Update Posted : December 12, 2017
Sponsor:
Information provided by (Responsible Party):
Johanna Savilampi, Region Örebro County

Brief Summary:
The purpose of the study is to evaluate the impact of different bolus volumes and viscosity on remifentanil-induced swallowing dysfunction in healthy volunteers.Hence, whether swallowing tasks can be done safer during sedation by altering bolus volumes and viscosities will be revealed. Furthermore, the study will clarify underlying mechanisms (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. If methylnaltrexone reverses the remifentanil-induced effects on swallowing, this would suggest a dominant peripherally mediated mechanism.

Condition or disease Intervention/treatment Phase
Pharyngeal Dysfunction Pharyngeal Swallowing Drug: RemifentanilMNTX Drug: PlaceboMNTX Phase 4

Detailed Description:

Monitored anesthesia care (MAC) is commonly applied in modern perioperative care and means that minor surgical procedures are accomplished in awake patients using local anesthesia and light sedation. MAC has many advantages compared to general anesthesia; the recovery time after anesthesia is shorter and risk for postoperative nausea is lower to mention some. However, the patient is spontaneously breathing and the airway is not protected by an endotracheal tube which potentially increases risk of pulmonary aspiration. Pulmonary aspiration, that is inhalation of stomach and/or pharyngeal contents into the lungs, is a severe anesthesia-related complication and can in worst case lead to pneumonia and even death. Intact swallowing function is crucial in avoiding aspiration and how sedatives and analgesic agents used during MAC influence swallowing function is not fully understood.

Pharyngeal function during bolus swallowing is measured by combined high resolution impedance manometry (HRIM). The HRIM catheter is inserted through the nose in such a way that sensors straddle the entire pharynx and esophagus with the distal catheter tip in the stomach. Dynamic pressure changes and flow can be detected during swallowing and data registered by HRIM are analysed using purpose-designed software, AIM analysis (automated impedance manometry analysis). AIM analysis derives pressure flow variables which describe different physiological events like bolus timing and bolus distension in the pharynx and the esophagus during swallowing. A Swallow Risk Index value, quantifying risk of deglutitive aspiration, can also be defined.

The aim of the study is to evaluate impact of different bolus volumes on remifentanil-induced swallowing dysfunction in healthy volunteers. The study will clarify underlying mechanisms (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. Furthermore, whether swallowing tasks can be done safer during sedation by altering bolus volumes will be revealed. In addition to bolus volume, different bolus viscosities will be tested. It is shown that higher bolus viscosity diminishes misdirected swallows in dysphagic patients and higher bolus viscosity may possibly counteracts the swallowing dysfunction induced by remifentanil. Moreover, if MNTX reverses the remifentanil-induced effects on swallowing, then this would suggest a dominant peripherally mediated mechanism. Our aim is also to evaluate impact of remifentanil exposure on esophageal motility and impact of methylnaltrexone alone on swallowing function.

20 healthy volunteers will be studied on two different occasions approximately one week apart. In a randomized order volunteers will receive intravenous infusion of remifentanil and an intravenous injection of MNTX on one occasion, and placebo (normal saline) infusion and an intravenous injection of MNTX on the other occasion. Blood samples are obtained for plasma concentration determination of the study drug and sedation levels are assessed during study drug exposure.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume: a Randomized, Double-Blind Study in Healthy Volunteers
Actual Study Start Date : November 11, 2017
Estimated Primary Completion Date : April 1, 2018
Estimated Study Completion Date : April 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: RemifentanilMNTX
Volunteers are given an intravenous infusion with remifentanil, with an effect-site target concentration of 3 ng/ml via a target-controlled infusion (TCI) pump. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given.
Drug: RemifentanilMNTX
Remifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg
Other Names:
  • Methylnaltrexone
  • Remifentanil
  • Relistor
  • Ultiva

Active Comparator: PlaceboMNTX
Volunteers are given an intravenous infusion with saline 0,9%. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given.
Drug: PlaceboMNTX
Placebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg
Other Names:
  • Sodium Chloride 0.9%
  • Methylnaltrexone
  • Relistor




Primary Outcome Measures :
  1. Pressure Flow pharyngeal variables, 10 ml vs 20 ml bolus [ Time Frame: Up to 60 minutes ]
    Difference in pharyngeal pressure flow variables during remifentanil exposure between bolus volumes of 10 ml and 20 ml compared to placebo.


Secondary Outcome Measures :
  1. Pressure Flow pharyngeal variables, liquid vs semisolid bolus [ Time Frame: Up to 60 minutes ]
    Difference in pharyngeal pressure flow variables during remifentanil exposure between liquid and semisolid boluses compared to placebo

  2. Pressure Flow pharyngeal variables, remifentanil before vs after methylnaltrexone [ Time Frame: Up to 60 minutes ]
    Difference in pharyngeal pressure flow variables during remifentanil exposure before and after methylnaltrexone administration compared to placebo.

  3. Pressure Flow pharyngeal variables, placebo before vs after methylnaltrexone [ Time Frame: Up to 60 minutes ]
    Difference in pharyngeal pressure flow variables during placebo infusion before and after methylnaltrexone administration.

  4. Pressure Flow esophageal motility variables, 10 ml vs 20 ml bolus [ Time Frame: Up to 60 minutes ]
    Difference in variables of esophageal motility between different bolus volumes during remifentanil exposure compared to placebo.

  5. Pressure Flow esophageal motility variables, liquid vs semisolid bolus [ Time Frame: Up to 60 minutes ]
    Difference in variables of esophageal motility between liquid and semisolid boluses during remifentanil exposure compared to placebo.

  6. Pressure Flow esophageal motility variables, remifentanil before vs after methylnaltrexone [ Time Frame: Up to 60 minutes ]
    Difference in variables of esophageal motility during remifentanil exposure before and after methylnaltrexone administration compared to placebo.

  7. Pressure Flow esophageal motility variables, placebo before vs after methylnaltrexone [ Time Frame: Up to 60 minutes ]
    Difference in variables of esophageal motility during placebo infusion before and after methylnaltrexone administration.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. ≥ 18 - ≤ 40 year old healthy volunteers from both sexes.
  2. Have signed and dated Informed Consent.
  3. Willing and able to comply with the protocol for the duration of the trial.

Exclusion Criteria:

  1. Anamnesis of pharyngoesophageal dysfunction.
  2. Known or history of gastrointestinal, severe cardiac, pulmonary or neurological disease
  3. Ongoing medication that may affect upper gastrointestinal tract, larynx or lower airway.
  4. Allergies to or history of reaction to remifentanil, fentanyl analogues or dexmedetomidine.
  5. Pregnancy or breast feeding
  6. BMI > 30
  7. Smoking
  8. Previous participation in a medicinal clinical trial during the last year where an opioid has been used or have during the last 30 days participated in any other medicinal clinical trial or in a trial where follow-up is not completed.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03283020


Contacts
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Contact: Johanna Savilampi, MD, PhD +46196020266 johanna.savilampi@regionorebrolan.se

Locations
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Sweden
Department of Anaesthesiology and Intensive Care, Örebro University Hospital Recruiting
Örebro, Sweden, 70185
Contact: Johanna Savilampi, Phd       johanna.savilampi@regionorebrolan.se   
Contact: Per Cajander, MD       per.cajander@regionorebrolan.se   
Sponsors and Collaborators
Region Örebro County
Investigators
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Principal Investigator: Johanna Savilampi, MD, PhD University hospital in Örebro
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Responsible Party: Johanna Savilampi, MD, PhD, Region Örebro County
ClinicalTrials.gov Identifier: NCT03283020    
Other Study ID Numbers: JS006
First Posted: September 14, 2017    Key Record Dates
Last Update Posted: December 12, 2017
Last Verified: December 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Johanna Savilampi, Region Örebro County:
Remifentanil
Methylnaltrexone
Pharyngeal dysfunction
Anesthetic sedation
Additional relevant MeSH terms:
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Naltrexone
Remifentanil
Methylnaltrexone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists
Alcohol Deterrents