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Status unknownNCT03283020Updated Dec 12, 2017

Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume

A Phase 4 interventional study of RemifentanilMNTX and PlaceboMNTX in Pharyngeal Dysfunction and Pharyngeal Swallowing, sponsored by Region Örebro County. Status unknown at 1 site in Sweden. Open to participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-12-12.

Sponsored by Region Örebro County · Phase 4, Interventional, and Basic science

The sponsor has not verified this record recently (last verified Dec 2017), so the status shown — last known as Recruiting — may be out of date.
Phase
Phase 4
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
18 Years to 40 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Pharyngeal Dysfunction
  • Pharyngeal Swallowing

Keywords

  • Remifentanil
  • Methylnaltrexone
  • Pharyngeal dysfunction
  • Anesthetic sedation
03

Who can participate

Ages eligible
18 Years to 40 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
04

Study design

Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
20 participants (estimated)

Study arms

  • 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

  • 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

Interventions

  • DrugRemifentanilMNTX

    Remifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg

    Also known as: Methylnaltrexone, Remifentanil, Relistor, Ultiva

  • DrugPlaceboMNTX

    Placebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg

    Also known as: Sodium Chloride 0.9%, Methylnaltrexone, Relistor

05

What researchers measure

Primary outcomes

  1. Pressure Flow pharyngeal variables, 10 ml vs 20 ml bolus

    Difference in pharyngeal pressure flow variables during remifentanil exposure between bolus volumes of 10 ml and 20 ml compared to placebo.

    Time frame: Up to 60 minutes

Secondary outcomes

  1. Pressure Flow pharyngeal variables, liquid vs semisolid bolus

    Difference in pharyngeal pressure flow variables during remifentanil exposure between liquid and semisolid boluses compared to placebo

    Time frame: Up to 60 minutes

  2. Pressure Flow pharyngeal variables, remifentanil before vs after methylnaltrexone

    Difference in pharyngeal pressure flow variables during remifentanil exposure before and after methylnaltrexone administration compared to placebo.

    Time frame: Up to 60 minutes

  3. Pressure Flow pharyngeal variables, placebo before vs after methylnaltrexone

    Difference in pharyngeal pressure flow variables during placebo infusion before and after methylnaltrexone administration.

    Time frame: Up to 60 minutes

  4. Pressure Flow esophageal motility variables, 10 ml vs 20 ml bolus

    Difference in variables of esophageal motility between different bolus volumes during remifentanil exposure compared to placebo.

    Time frame: Up to 60 minutes

  5. Pressure Flow esophageal motility variables, liquid vs semisolid bolus

    Difference in variables of esophageal motility between liquid and semisolid boluses during remifentanil exposure compared to placebo.

    Time frame: Up to 60 minutes

  6. Pressure Flow esophageal motility variables, remifentanil before vs after methylnaltrexone

    Difference in variables of esophageal motility during remifentanil exposure before and after methylnaltrexone administration compared to placebo.

    Time frame: Up to 60 minutes

  7. Pressure Flow esophageal motility variables, placebo before vs after methylnaltrexone

    Difference in variables of esophageal motility during placebo infusion before and after methylnaltrexone administration.

    Time frame: Up to 60 minutes

06

Study locations

1 of 1 sites recruiting
07

Registry details

Key details

Study ID
NCT03283020
Lead sponsor
Region Örebro County
Responsible party
Johanna Savilampi (MD, PhD, Region Örebro County) — Principal investigator
First posted
Sep 14, 2017
Start date
Nov 11, 2017
Primary completion
Apr 1, 2018 (estimated)
Completion
Apr 1, 2018 (estimated)
Last update
Dec 12, 2017

Study contacts

Johanna Savilampi, MD, PhD
Contact
johanna.savilampi@regionorebrolan.se
+46196020266
Johanna Savilampi, MD, PhD
principal investigator · University hospital in Örebro

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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