Impact of Amantadine on Traumatic Brain Injury

Potential Impact of Amantadine on Traumatic Brain Injury Outcomes

The aim of this study is to evaluate whether the addition of amantadine to the management regimen of traumatic brain injury patients would have a favorable effect on recovery and neurological complications in association with prognosis biomarkers Interleukin-18 (IL-18), Neuron-specific enolase (NSE) and (Neurotensin).

Study Overview

• Status: Completed
• Conditions: Trauma, Brain
• Intervention / Treatment: Drug: Amantadine (100mg) as add on therapy.; Drug: Placebo

Detailed Description

Proposal Steps

1. Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University.
2. All participants agreed to take part in this clinical study and provide informed consent.
3. Patients will be enrolled if they present with clinical signs of trauma, from Emergency department at Tanta University Hospital
4. Complete physical, laboratory, radiological assessment will be done for all patients
5. Serum samples will be collected for measuring the biomarkers.
6. All enrolled 50 patients will be divided into two groups; Group I are patients who will receive amantadine as added on therapy. Group II are patients who will be managed with the standard regimen.
7. All patients will be followed up during 6 weeks period.
8. At the end of 6 weeks, prognosis biomarkers will be withdrawn.
9. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.
10. Measuring outcome: The primary outcome is to compare the effect of adding amantadine on recovery rate and neurological complications in trauma patients.
11. Results, conclusion, discussion and recommendations will be given.

Methodology

• 50 Patients will be randomized equally to the assigned study groups
• Prognosis biomarkers (IL-18, NSE and Neurotensin) will be measured using ELISA
• Conventional routine tests (including renal function tests) will be assessed
• Patients will be evaluated clinically (such as Glasgow score…) for recovery rate for neurological complications.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Elgarbia
    • Tanta, Elgarbia, Egypt, 31527
      • Tanta University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Inclusion criteria

  •Adult patients will be enrolled if they present with clinical signs of trauma brain injury

• Exclusion criteria

  • Age lower than 18
  • Females with positive pregnancy test
  • Known congestive heart failure or ischemic heart disease
  • Any injury disturbs the examination (high cervical cord injury or locked-in syndrome, could be a source of bias)
  • Penetrating head trauma
  • Need for any operation (laparotomy or craniotomy)
  • Severe brain disease (For example CVA history or brain tumour)
  • Renal failure with GFR lower than 60 ml/min
  • Patients with unknown identity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amantadine Group; Group, I are patients who will receive amantadine (100mg) as add on therapy to the standard regimen.	Drug: Amantadine (100mg) as add on therapy.; Amantadine (100mg) as add on therapy to the management regimen of traumatic brain injury - 100mg twice daily Oral or feeding tube; Other Names: PK-merz
Placebo Comparator: Placebo Group; Group II are patients who will be managed with the standard regimen.	Drug: Placebo; patients will be managed with placebo as add on to the standard regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU stay (days)	ICU stay (days)	6 weeks
Neurotensin pg/ml	Neurotensin pg/ml by ELISA Kit	2 weeks
Neuron specific enolase (NSE) ng/mL	Neuron specific enolase (NSE) by ELISA Kit	2 Weeks
interleukin-18 (IL-18) pg/ml	interleukin-18 (IL-18) by ELISA Kit	2 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(GCS) Total Glasgow Coma Scale score: (Severe: GCS 8 or less- Moderate: GCS 9-12- Mild: GCS 13-15).	number of GCS to describe the level of consciousness in a person following a traumatic brain injury.	6 weeks
GCS-E	The Glasgow Outcome Scale-Extended (GOS-E)	6 months

Collaborators and Investigators

• Sponsor: Damanhour University
• Investigators: Study Director: Rehab H Werida, Lecturer, Damanhour University

Publications and helpful links

General Publications

• Stelmaschuk S, Will MC, Meyers T. Amantadine to Treat Cognitive Dysfunction in Moderate to Severe Traumatic Brain Injury. J Trauma Nurs. 2015 Jul-Aug;22(4):194-203; quiz E1-2. doi: 10.1097/JTN.0000000000000138.
• Bharosay A, Bharosay VV, Varma M, Saxena K, Sodani A, Saxena R. Correlation of Brain Biomarker Neuron Specific Enolase (NSE) with Degree of Disability and Neurological Worsening in Cerebrovascular Stroke. Indian J Clin Biochem. 2012 Apr;27(2):186-90. doi: 10.1007/s12291-011-0172-9. Epub 2011 Nov 8.
• Ciaramella A, Della Vedova C, Salani F, Viganotti M, D'Ippolito M, Caltagirone C, Formisano R, Sabatini U, Bossu P. Increased levels of serum IL-18 are associated with the long-term outcome of severe traumatic brain injury. Neuroimmunomodulation. 2014;21(1):8-12. doi: 10.1159/000354764. Epub 2013 Sep 26.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): October 30, 2021

Study Registration Dates

• First Submitted: August 22, 2020
• First Submitted That Met QC Criteria: August 22, 2020
• First Posted (Actual): August 26, 2020

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: traumatic brain injury (TBI); Interleukin-18 (IL-18); Neuron specific enolase (NSE); Neurotensin (NT)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; 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: Amantadine on TBI

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