Oral Amantadine, IV Amantadine and Hemodynamic Response to Laryngoscopy

Oral Amantadine Versus IV Amantadine to Attenuate the Hemodynamic Response to Laryngoscopy, Tracheal Intubation and Surgical Incision and Their Effect on β-endorphin: A Randomized Clinical Trial

this study will be undertaken-to evaluate the effect of oral amantadine versus IV amantadine premedication on the hemodynamic response to laryngoscopy ,tracheal intubation and surgical incision and their effect on β-endorphins.

Study Overview

• Status: Recruiting
• Conditions: Intubation, Intratracheal
• Intervention / Treatment: Drug: oral Amantadine sulfate; Drug: i.v Amantadine Sulfate; Drug: placebo 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 .Amantadine 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.. 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.

this study will be undertaken-to evaluate the effect of oral amantadine versus IV amantadine premedication on the hemodynamic response to laryngoscopy ,tracheal intubation and surgical incision and their effect on β-endorphins.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ghada Abu El Fadl, MD; Phone Number: 01005802086; Email: ghadafadl77@gmail.com
• Study Contact Backup: Name: amani abd elwahab, MD; Phone Number: 01004610623; Email: amanihassan1978@yahoo.com

Study Locations

• Egypt
  • Assiut, Egypt
    • Recruiting
    • Assiut university hospitals
    • Contact: Ghada Abu El Fadl, MD; Phone Number: 01005802086; Email: ghadafadl77@gmail.com
    • Contact: amani abd elwahabMD, MD; Phone Number: 01004610623; Email: amanihassan1976@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA I&II
• the age range 20-55 years scheduled for elective back surgery(laminectomy, discectomy and spinal canal stenosis)

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)
• DM, 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: oral group; the patients will receive oral amantadine sulfate using the dose 100 mg 90 minute prior to the surgery and infusion of100cm I.V saline	Drug: oral Amantadine sulfate; oral amantadine; Other Names: amantadine
Active Comparator: I.V group; the patients will receive 100 mg I.V amantadine sulfate infusion over 60minute prior to the surgery and placebo tablet 90 minute prior to the surgery	Drug: i.v Amantadine Sulfate; intra venous amantadine; Other Names: PK-Merz
Placebo Comparator: control group (group C); the patients will receive placebo tablet 90 minute prior to the surgery and infusion of 100cm I.V saline over 60minute prior to the surgery	Drug: placebo tablet; placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the effect of oral amantadine versus IV amantadine premedication on laryngoscopy and tracheal intubation on β-endorphins .	changes of the mean arterial blood pressure (mmhg)	baseline( before medication) , 5 minutes before induction of anaesthesia, 3 minutes after induction , 5 minutes after tracheal intubation and 5 minutes after skin incision

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the effect of oral amantadine versus IV amantadine premedication on the hemodynamic response to surgical incision	β-endorphins level in the blood	2 blood samples one just before medication and the second after 10 minutes after skin incision

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Ghada Abu El Fadl, MD, Assiut, Assiut governorate, Egypt, 715715

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2018
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (Actual): August 2, 2018

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 12, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: tracheal intubation; oral amantadine; IV amantadine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Amantadine
• Other Study ID Numbers: 17300205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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