Oral Amantadine Versus Gabapentin to Attenuate the Response to Laryngoscopy and Tracheal Intubation (15/5/2017)

Oral Amantadine Versus Gabapentin to Attenuate the Hemodynamic Response to Laryngoscopy and Tracheal Intubation and Their Effect on β-endorphin

To evaluate the effect of oral amantadine versus gabapentin premedication on the hemodynamic response to laryngoscopy and tracheal intubation and their effect on β-endorphins.

Study Overview

• Status: Completed
• Conditions: Effect of Laryngoscopy and Tracheal Intubation
• Intervention / Treatment: Other: oral amantadine sulfate; Drug: oral gabapentin; Drug: Placebo Oral Tablet

Detailed Description

Direct laryngoscopy and passage of endotracheal tube through the larynx is a noxious stimulus, which can provoke untoward response in the cardiovascular, respiratory and other physiological systems. Gabapentin, is 1-aminomethyl cyclohexane acetic acid.Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA). Gabapentin act in central nervous system CNS), it acts by decreasing the synthesis of neurotransmitter glutamate and by binding to the alpha 2 delta subunits of voltage dependent calcium channels.

Amantadine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and compared to ketamine, it is well tolerated with fewer side effects (mainly dizziness, sedation, and dry mouth). Amantadine's formulation permits the oral route for drug delivery, as well as the IV route. The side-effects profile of amantadine via all routes seems not to be harmful in appropriate dosages.. Amantadine has been clinically used as an antiviral drug, for dementia, and in the treatment of Parkinson's disease and spasticity. It is a non-competitive NMDA receptor antagonist, and compared to ketamine, it is well tolerated with fewer side effects (mainly dizziness, sedation, and dry mouth). Amantadine's formulation permits the oral route for drug delivery, as well as the IV route. The side-effects profile of amantadine via all routes seems not to be harmful in appropriate dosages.

In the central nervous system, beta-endorphins bind mu-opioid receptors and exert their primary action at presynaptic nerve terminals. However, instead of inhibiting substance P, they exert their analgesic effect by inhibiting the release of GABA, an inhibitory neurotransmitter, resulting in excess production of dopamine.

The investigators designed this study to prove the efficacy of oral amantadine versus gabapentin premedication on the hemodynamic response to laryngoscopy and tracheal intubation and their effect on β-endorphins.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Assiut university hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA I&II scheduled for elective spine surgery

Exclusion Criteria:

• Patient refusal
• Patients with ASA score III (with chronic kidney, lungs, Gastrointestinal tract, liver, or cardiovascular diseases)
• Pregnant or breastfeeding women.
• Allergy to any of the study medications and taking medications that could significantly interact with amantadine (tramadol, atropine, antipsychotic medications)
• diabetes mellitus, thyroid disease any endocrine disease
• Suspected difficult intubation or intubation time more than 30 second.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: amantadine group (Group A); the patients will receive oral amantadine sulfate using the dose 100 mg 120 minutes prior to the surgery, 5 ml saline IV 5 minutes before intubation.	Other: oral amantadine sulfate; In amantadine group:the patients will receive100 mg oral amantadine sulfate 90 minute prior to the surgery; Other Names: infex
Active Comparator: gabapentin group(Group B); the patients will receive oral gabapentin using the dose 800 mg 120 minutes prior to surgery,5 ml saline IV 5 minutes before intubation.	Drug: oral gabapentin; In gabapentin group: the patients will receive oral 800 mg gabapentin 90 minute prior to the surgery; Other Names: gabapentin
Placebo Comparator: control group (group C); the patients will receive placebo oral tablet 120 minutes prior to surgery, IV fentanyl 2µ/kg in 5 ml saline 5 minutes before intubation.	Drug: Placebo Oral Tablet; in control group : the patients will receive Placebo Oral Tablet 90 minute prior to the surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of oral amantadine versus gabapentin premedication on laryngoscopy and tracheal intubation on β-endorphins.	analysis of change of β-endorphins in blood sample	baseline blood sample taken before drug administration and after 15 minutes after intubation and before skin incision

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of oral amantadine versus gabapentin premedication on the Mean arterial blood pressure due to laryngoscopy and tracheal intubation	change of Mean arterial blood pressure	baselineMAP before drug administration and after 15 minutes after intubation and before skin incision
effect of oral amantadine versus gabapentin premedication on the heart rate due to laryngoscopy and tracheal intubation	change of heart rate	baseline heart rate before drug administration and after 15 minutes after intubation and before skin incision

Collaborators and Investigators

• Sponsor: Ghada Mohammed AboelFadl
• Investigators: Principal Investigator: Abualauon Elpiplaoy, MD, Assiut University; Study Chair: Ahmed El shanawany, MD, Assiut University; Principal Investigator: Azza Abo Elfadl El Sayed, MD, Assiut University

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2017
• Primary Completion (Actual): May 15, 2018
• Study Completion (Actual): May 15, 2018

Study Registration Dates

• First Submitted: May 20, 2017
• First Submitted That Met QC Criteria: May 29, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): September 25, 2018
• Last Update Submitted That Met QC Criteria: September 21, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: β-endorphins,laryngoscopy and tracheal intubation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Gabapentin; Amantadine
• Other Study ID Numbers: Assuit universty

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