Effectiveness Of High Dose Melatonin As Adjunctive Therapy For Dengue Fever With Warning Signs

Effectiveness Of High Dose Melatonin As Adjunctive Therapy For Pediatric Patients Diagnosed With Dengue Fever With Warning Signs: A Randomized Control Trial

Dengue Hemorrhagic Fever is a mosquito-borne viral disease endemic in the Philippines which caused multiple epidemics. Most points to the activation of the complement system secondary to humoral respond leading to cytokine release causing systemic inflammation. Melatonin, is a hormone which has an a) anti-viral, b) immunomodulator, c) antioxidant, d) modulatory effect on hematopoiesis and e) anti-inflammatory action.

This is a randomized control trial to determine the effectiveness of adjunctive melatonin therapy among patients diagnosed with Dengue fever with Warning Signs. This would include children aged 5 to 18 years old with no signs of hemmorhagic shock. They would be randomly assigned into 2 groups. Baseline Complete blood count with platelet (CBCPC) will be collected. Daily CBCPC will be collected and would be statistically analyze after the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Dengue Fever With Warning Signs
• Intervention / Treatment: Drug: Melatonin 20 MG

Detailed Description

Dengue Hemorrhagic Fever is a mosquito-borne viral disease endemic in the Philippines which caused multiple epidemics. Most points to the activation of the complement system secondary to humoral respond leading to cytokine release causing systemic inflammation. Melatonin, is a hormone which has an a) anti-viral, b) immunomodulator, c) antioxidant, d) modulatory effect on hematopoiesis and e) anti-inflammatory action.

Main Objective:

To determine the effectiveness of Melatonin tablet as an adjunctive therapy in decreasing morbidity for pediatric patients diagnosed with Dengue Fever with Warning Signs at Ilocos Training and Regional Medical Center Department of Pediatrics.

Specific Objective

1. To determine the clinical profiles of pediatric patients diagnosed with Dengue Fever with Warning Signs in Ilocos Training and Regional Medical Center

2. To determine the effectiveness of Melatonin 20mg as adjunctive therapy for pediatric patients diagnosed with Dengue Fever with Warning Signs with regards to:

   a. Number of days for resolution of fever from the 1st day of administration of melatonin b. Number of days for the platelet count to increase from the 1st day of administration of melatonin c. Number of days for the white blood cell count to increase from the 1st day of administration of melatonin d. Absence of subsequent complications in the critical phase of the illness (4th - 6th day of illness) i. Presence of mucosal bleeding, melena, epistaxis ii. Presence of ascites, pleural effusion, edema iii. Hypotension, tachycardia iv. Increase capillary refill time

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Navid P Roodaki, MD; Phone Number: +63 917 309 3931; Email: navidroodaki2391@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Patient aged 5 to 18 years old with febrile episodes (Temperature >/= 37.8 degrees Celsius) with positive Dengue NS1.

  2. Patients with Dengue Fever on the Department of Health 2012 definition of Dengue fever with Warning Signs with any one of the following:

  1. Abdominal tenderness
  2. Persistent vomiting
  3. Minimal mucosal bleed

  4. Platelet count less than or equal to 100,000

     Exclusion Criteria:

• 1. Patients with signs and symptoms related to dengue fever but with negative Dengue Ns1 result.

  2. Patients diagnosed as Severe Dengue or Dengue Shock. 3. Patients unable to tolerate tablet formulation. 4. Patients placed on nothing per Orem. 5. Patients previously treated in a referring facility.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Other than the guided management of Dengue Fever with warning signs, the treatment group will receive a standard dose of 20mg/day of melatonin20-21 for 5 days. The dosing was based on the study by Leiberman et al and Malhotra et al. If a patient is unable to tolerate the whole or punctured tablet, it will be given with milk or water. There is no known interaction between melatonin and milk known to date. Daily complete blood count will be done and be recording in an electronic record using Microsoft Excel.	Drug: Melatonin 20 MG; Melatonin, also known as N-acetyl-5-methoxytryptamine will be the main intervention given to participating patients of this study. This study will use a dose of 20mg/day using the commercially available 5mg/tablet20-21. If a patient cannot be tolerate swallowing the whole tablet, it will be crushed and mixed with milk. According to the study done by Shah et al. there was no degradation in the active component of melatonin when mixed with milk or food as a medium for drug delivery.
No Intervention: Control Group; Other than the guided management of Dengue Fever with warning signs, the control group will be manage according the Department of Health Dengue Management Guideline. No placebo will be given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Of Days Prior To Elevation of Platelet Count Among Dengue Fever with Warningn Signs Patient Given Melatonin 20mg.	Effectiveness Of Melatonin Tablet As An Adjunctive Therapy In Decreasing Morbidity For Pediatric Patients Diagnosed With Dengue Fever With Warning Signs	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Of Dengue Fever with Warning Signs among Pediatric Population at Ilocos Training and Regional Medical Center.	Clinical Profiles Of Pediatric Patients Diagnosed With Dengue Fever With Warning Signs In Ilocos Training And Regional Medical Center	1 year
determine the effectiveness of Melatonin 20mg as adjunctive therapy for pediatric patients diagnosed with Dengue Fever with Warning Signs	Number of days for the platelet count to increase from the 1st day of administration of melatonin; Number of days for the white blood cell count to increase from the 1st day of administration of melatonin; Absence of subsequent complications in the critical phase of the illness (4th - 6th day of illness) i. Presence of mucosal bleeding, melena, epistaxis ii. Presence of ascites, pleural effusion, edema iii. Hypotension, tachycardia iv. Increase capillary refill time	1 year
Number Of Days Prior To Elevation of White Blood Cells Among Dengue Fever with Warningn Signs Patient Given Melatonin 20mg.	Effectiveness Of Melatonin Tablet As An Adjunctive Therapy In Decreasing Morbidity For Pediatric Patients Diagnosed With Dengue Fever With Warning Signs	1 year

Collaborators and Investigators

• Sponsor: Ilocos Training and Regional Medical Center
• Investigators: Study Chair: Ma. Lydia O Ramirez, MD, Ilocos Training and Regional Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): October 20, 2021
• Primary Completion (Anticipated): August 30, 2022
• Study Completion (Anticipated): October 30, 2022

Study Registration Dates

• First Submitted: August 22, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Hemorrhagic Fevers, Viral; Fever; Dengue; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: ITRMC-REC-2020-045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Due to the Data Privacy Act of the Philippines, only the completed data will be shared

Drug and device information, study documents

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