Clinical trial NCT03390972: Dexmedetomidine and Swallowing Function
Official title: Effects of Dexmedetomidine on Swallowing Function: a Randomized, Double-Blind Study in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Deglutition
Keywords: Dexmedetomidine
Swallowing function
Anesthetic sedation
Lead sponsor: Region Örebro County
Sponsor class: OTHER
First posted: 2018-01-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility 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. 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.

Primary outcomes:
measure: Swallow Risk Index, dex vs baseline
timeFrame: 60 minutes
measure: Hypopharyngeal Intrabolus Pressure, dex vs baseline
timeFrame: 60 min
measure: Mean Distension Contraction Latency, dex vs baseline
timeFrame: 60 min
measure: Hypopharyngeal Bolus Presence Time, dex vs baseline
timeFrame: 60 min
measure: Velopharyngeal to Tongue Base Pressure Integral, dex vs baseline
timeFrame: 60 min
measure: Hypopharyngeal Contractile Integral, dex vs baseline
timeFrame: 60 min
measure: Mean Pharyngeal Peak Pressure, dex vs baseline
timeFrame: 60 min
measure: Mean UES Basal Pressure, dex vs baseline
timeFrame: 60 min
measure: UES Open Time, dex vs baseline
timeFrame: 60 min
measure: UES Maximum Admittance
timeFrame: 60 min
measure: UES Integrated Relaxation Pressure
timeFrame: 60 min
Secondary outcomes:
measure: Pharyngeal Pressure Flow variables, dex 0.6 ng/ml vs 1.2 ng/ml
timeFrame: 60 minutes
measure: Esophageal pressure flow variables, dex vs baseline
timeFrame: 60 min
measure: Esophageal pressure flow variables, dex 0.6 ng/ml vs 1.2 ng/ml
timeFrame: 60 min
measure: Subjective swallowing difficulties
timeFrame: 60 minutes
Other outcomes:
Locations:
Study officials:
affiliation: Department of Anaesthesiology and Intensive Care, Örebro University Hospital
name: Johanan Savilampi, Phd
role: PRINCIPAL_INVESTIGATOR
References: