Dexmedetomidine and Swallowing Function (DexSwallow)

Effects of Dexmedetomidine on Swallowing Function: a Randomized, Double-Blind Study in Healthy Volunteers

The purpose of the study is to evaluate the impact of dexmedetomidine on swallowing function in healthy volunteers using combined pressure and impedance recordings. Furthermore, two different concentrations of dexmedetomidine will be studied to find out whether any posible impact of dexmedetomidine on swallowing function is dose-dependent.

Study Overview

• Status: Unknown
• Conditions: Deglutition
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Placebo

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 dexmedetomidine on swallowing function in healthy volunteers.Dexmedetomidine is a selective alfa-agonist frequently used during MAC. Furthermore, two different concentrations of dexmedetomidine will be studied to find out whether any posible impact of dexmedetomidine on swallowing function is dose-dependent. Moreover, subjective swallowing difficulties will be assessed.

20 healthy volunteers will be studied on two different occasions approximately one week apart. In a randomized order volunteers will receive intravenous infusion of dexmedetomidine in two subsequent concentrations and placebo (normal saline) infusion in corresponding doses 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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Johanna Savilampi, Phd; Phone Number: +46 019 6020266; Email: johanna.savilampi@regionorebrolan.se
• Study Contact Backup: Name: Per Cajander, MD; Phone Number: +46 019 6020353; Email: per.cajander@regionorebrolan.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. Known heart rhythm disorder.
6. Tendency to faint.
7. Pregnancy or breast feeding
8. BMI > 30
9. Smoking
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine; Volunteers are given an intravenous infusion with dexmedetomidine, with an effect-site target concentration of 0.6 ng/ml via a target-controlled infusion (TCI) pump. After a series of swallowing tests the effect-site target concentration is raised to 1.2 ng/ml and the swallowing series is repeated.	Drug: Dexmedetomidine; Dexmedetomidine TCI 0.6 ng/ml and 1.2 ng/ml; Other Names: Dexdor
Placebo Comparator: Placebo; Volunteers are given an intravenous infusion with saline 0,9% with target controlled infusion pump in corresponding doses as in the dexmedetomidine arm.	Drug: Placebo; Placebo (NaCl 0.9%) TCI infusion; Other Names: Sodium Chloride 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Swallow Risk Index, dex vs baseline	Global measure of swallowing dysfunction related to aspiration risk, during swallowing between dexmedetomidine exposure and baseline compared to placebo.	60 minutes
Hypopharyngeal Intrabolus Pressure, dex vs baseline	Measure of pharyngeal outflow resistance, mmHg	60 min
Mean Distension Contraction Latency, dex vs baseline	Measure of flow timing, sec	60 min
Hypopharyngeal Bolus Presence Time, dex vs baseline	Measure of bolus arrival/oral bolus control, sec	60 min
Velopharyngeal to Tongue Base Pressure Integral, dex vs baseline	Measure of lumen occlusive pressure, mmHgxsxcm	60 min
Hypopharyngeal Contractile Integral, dex vs baseline	Measure of lumen occlusive pressure, mmHgxsxcm	60 min
Mean Pharyngeal Peak Pressure, dex vs baseline	Measure of lumen occlusive pressure, mmHg	60 min
Mean UES Basal Pressure, dex vs baseline	Measure of UES (upper esophageal sphincter) basal tone, mmHg	60 min
UES Open Time, dex vs baseline	Measure of UES opening, sec	60 min
UES Maximum Admittance	Measure of UES opening, ms	60 min
UES Integrated Relaxation Pressure	Measure of UES relaxation, mmHg	60 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharyngeal Pressure Flow variables, dex 0.6 ng/ml vs 1.2 ng/ml	Difference in pressure flow variables during swallowing between dexmedetomidine target concentration of 0.6 ng/ml and 1.2 ng/ml compared to placebo.	60 minutes
Esophageal pressure flow variables, dex vs baseline	Difference in pressure flow variables during swallowing between dexmedetomidine exposure and baseline compared to placebo.	60 min
Esophageal pressure flow variables, dex 0.6 ng/ml vs 1.2 ng/ml	Difference in esophageal pressure flow variables during swallowing between dexmedetomidine target concentration of 0.6 ng/ml and 1.2 ng/ml compared to placebo.	60 min
Subjective swallowing difficulties	Difference in subjective swallowing difficulties between dexmedetomidine exposure and baseline compared to placebo.	60 minutes

Collaborators and Investigators

• Sponsor: Region Örebro County
• Investigators: Principal Investigator: Johanan Savilampi, Phd, Department of Anaesthesiology and Intensive Care, Örebro University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 22, 2018
• Primary Completion (Anticipated): April 11, 2018
• Study Completion (Anticipated): April 11, 2018

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: December 28, 2017
• First Posted (Actual): January 5, 2018

Study Record Updates

• Last Update Posted (Actual): January 5, 2018
• Last Update Submitted That Met QC Criteria: December 28, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Dexmedetomidine; Anesthetic sedation; Swallowing function
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: JS007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No