Combination Momordica Charantia Extract and Primaquine Againts Plasmodium Falciparum Uncomplicated and Plasmodium Vivax Uncomplicated Treatment in Manokwari, West Papua (MCMPFPB)

Comparing the efficacy of the combination treatment of bitter melon fruit extract (Momordica charantia) with primaquine (MC+PQ) against the combination of dihydroartemisinin + piperaquine + primaquine (DHP+PQ) on patients with Plasmodium falciparum and Plasmodium vivax without complications in Manokwari, West Papua, Indonesia. The research was conducted from January 2019 to April 2019 at Manokwari Regional General Hospital, West Papua. Open label, 2 parallel randomized clinical studies with Plasmodium falciparum malaria patients without complications (Study 1) and patients with Plasmodium vivax malaria without complications (Study 2). The randomized clinical trial divided in 2 treatment groups, namely the MC+PQ and DHP+PQ. The Success of the treatment was determined by the combination of blood schizontocidal therapy in radical cure. The overall final assessed results were the average value of parasitological failure, hematological measurements, liver function, kidney function, blood lipid levels, blood glucose levels and adverse events until day 42.

Study Overview

• Status: Completed
• Conditions: Infections; Malaria; Malaria, Vivax; Uncomplicated Malaria; Malaria,Falciparum; Uncomplicated Plasmodium Falciparum
• Intervention / Treatment: Drug: Dihydroartemisinin; Drug: Piperaquine; Drug: Primaquine; Other: Momordica Charantia Extract

Detailed Description

Every group therapy session was under team member supervision, required to complete follow-up visits on days 1, 2, 3, 5, 7, 14, 21, 28, 35, and 42. All of the studies 1 and 2 was split into more than two treatment groups, MC+PQ and DHP+PQ. The study was broken up into several 2 studies. Plasmodium falciparum patients without complications (n = 50 in each study) were the subjects of study 1, and Plasmodium vivax patients without complications (n = 50) were the subjects of studies 2 and 3.

The combination of 500 mg of bitter melon fruit extract (Momordica charantia) and 325 mg of bitter melon fruit content (13.50 mg/kg body weight) was initially approved by the MC+PQ group and administered for 3 days. 15 mg Primaquine dose single (0.25 mg/kg body weight) was administered for patients with Plasmodium falciparum and Plasmodium vivax malaria. Patients with Plasmodium falciparum malaria was treated for the first 14 days, while those with Plasmodium vivax malaria were treated for 14 days.

The 2nd DHP+PQ group received three days of DHP (fixed dose combination tablets of 40 mg dihydroartemisinin and 320 mg piperaquine; DHP-FRIMAL, Mersi pharmaceutical, Tbk) in addition to 15 mg primaquine that had previously been given for one day to patients with Plasmodium falciparum who had no complications and for 14 days to those with Plasmodium vivax. DHP renewal is determined by body weight (age 15 years, >40-60 kg: 3 tablets; >60-80 kg: 4 tablets; 80 kg: 5 tablets)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Indonesia
  • West Papua
    • Manokwari, West Papua, Indonesia
      • Manokwari Regional General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• incomplete therapy patients
• Age ≥15 years old male or female up to 60 years old.
• diagnosis and an outcome inspection microscopically suffering from Plasmodium falciparum malaria or Plasmodium vivax with density parasites 1000-100,000/µL
• History of fever within the past 24-48 hours with axillary temperature ≥ 37.5°C
• There were no signs of severe malaria
• had no chronic disease
• willing to follow up for 42 days; No consuming other antimalarial drugs within 2 weeks; willingly to participate in investigations and follow established procedures (informed consent)

Exclusion Criteria:

• pregnant female, breastfeeding female, children and infants
• suffering a mental disturbance, heavy illness like kidney, liver, tuberculosis, cancer, AIDS and other heavy diseases
• one set of symptom or signs of severe malaria
• had a history of hypersensitivity, allergies, and antimalarial contraindications
• not willingly to follow the inquiry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bitter melon fruit extract (Momordica charantia) with primaquine; For three days, a combination of 500 mg of bitter melon fruit extract (Momordica charantia) and 325 mg of bitter melon fruit content (13.50 mg/kg body weight) was administered. those with Plasmodium falciparum and Plasmodium vivax malaria received a single dosage of primaquine (0.25 mg/kg body weight) once daily, with those with Plasmodium falciparum malaria receiving it for 14 days.	Drug: Primaquine; Primaquine dose 0.25 mg/kg body weight given to uncomplicated Plasmodium falciparum patients on the first day only; Other: Momordica Charantia Extract; Momordica charantia extract capsules at a dose of 325 mg were given to patients for 3 days
Active Comparator: dihydroartemisinin+piperaquine+ primaquine; DHP (fixed dosage combination tablets containing 40 mg dihydroartemisinin and 320 mg piperaquine) was administered to the group for 3 days, with primaquine being administered for 14 days to patients with Plasmodium vivax and 1 day initially to those with Plasmodium falciparum without difficulties. Body weight is taken into consideration while setting therapy parameters (age 15 years, >40-60 kg: 3 tablets; >60-80 kg: 4 tablets; 80 kg: 5 tablets).	Drug: Dihydroartemisinin; dihidroartemisinin dose of 2-4 mg/Kg Body weight taken for 3 days; Drug: Piperaquine; piperaquine at a dose of 16-32 mg/Kg body weight taken for 3 days; Drug: Primaquine; Primaquine dose 0.25 mg/kg body weight given to uncomplicated Plasmodium falciparum patients on the first day only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
development of sexual and asexual stages of Plasmodium falciparum	Finger prick blood samples are collected for malaria blood smear. Thick and thin blood smear were stained with 3% giemsa solution for 45 minutes and were read under binocular microscope with 1,000x magnification	0, 14, 28, and 42 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parasite clearence times	parasite reduction ratio	0, 14, 28, and 42 days post-treatment
Fever clearance time	time taken for the axilla temperature to fall below 37.5°C in patients who were febrile at inclusion	0, 14, 28, and 42 days post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin measurement	Hematological study, measure in g/dl	0, 14, 28, and 42 days post-treatment
Erytrocytes measurement	Hematological study, measure in 10^6/mm³	0, 14, 28, and 42 days post-treatment
Hematocrits measurement	Hematological study, measure in %	0, 14, 28, and 42 days post-treatment
Thrombocytes measurement	Hematological study, measure in 10^3/mm³	0, 14, 28, and 42 days post-treatment
Leucocytes measurement	Hematological study, measure count in 1 µL	0, 14, 28, and 42 days post-treatment
Albumin measurement	Hematological study, measure in mg%	0, 14, 28, and 42 days post-treatment
AST/SGOT measurement	Blood chemistry, measure in µ/mL	0, 14, 28, and 42 days post-treatment
total bilirubin measurement	Blood chemistry, measure in mg %	0, 14, 28, and 42 days post-treatment
Direct bilirubin measurement	Blood chemistry, measure in mg %	0, 14, 28, and 42 days post-treatment
Total protein measurement	Blood chemistry, measure in mg %	0, 14, 28, and 42 days post-treatment
Creatinine measurement	Blood chemistry, measure in mg %	0, 14, 28, and 42 days post-treatment
Ureum measurement	Blood chemistry, measure in mg %	0, 14, 28, and 42 days post-treatment
Gout measurement	Blood chemistry, measure in mg %	0, 14, 28, and 42 days post-treatment
Total Cholesterol measurement	Lipid parameter, measure in mg/dL	0, 14, 28, and 42 days post-treatment
Triglycerides measurement	Lipid parameter, measure in mg/dL	0, 14, 28, and 42 days post-treatment
Glucose measurement	Glucose parameter, measure in mg/dL	0, 14, 28, and 42 days post-treatment

Collaborators and Investigators

• Sponsor: Syamsudin Abdillah,Ph.D, Pharm D
• Collaborators: Cipto Mangunkusumo Hospital; PT Natura Nuswantara Nirmala

Publications and helpful links

General Publications

• Abdillah S, Tambunan RM, Sinaga YM, Farida Y. Ethno-botanical survey of plants used in the traditional treatment of malaria in Sei Kepayang, Asahan of North Sumatera. Asian Pac J Trop Med. 2014 Sep;7S1:S104-7. doi: 10.1016/S1995-7645(14)60213-3.
• Jia S, Shen M, Zhang F, Xie J. Recent Advances in Momordica charantia: Functional Components and Biological Activities. Int J Mol Sci. 2017 Nov 28;18(12):2555. doi: 10.3390/ijms18122555.
• Chen F, Huang G, Yang Z, Hou Y. Antioxidant activity of Momordica charantia polysaccharide and its derivatives. Int J Biol Macromol. 2019 Oct 1;138:673-680. doi: 10.1016/j.ijbiomac.2019.07.129. Epub 2019 Jul 22.
• Wang S, Liu Q, Zeng T, Zhan J, Zhao H, Ho CT, Xiao Y, Li S. Immunomodulatory effects and associated mechanisms of Momordica charantia and its phytochemicals. Food Funct. 2022 Nov 28;13(23):11986-11998. doi: 10.1039/d2fo02096c.
• Nelwan EJ, Ekawati LL, Tjahjono B, Setiabudy R, Sutanto I, Chand K, Ekasari T, Djoko D, Basri H, Taylor WR, Duparc S, Subekti D, Elyazar I, Noviyanti R, Sudoyo H, Baird JK. Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia. BMC Med. 2015 Dec 11;13:294. doi: 10.1186/s12916-015-0535-9.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2019
• Primary Completion (Actual): April 16, 2019
• Study Completion (Actual): April 16, 2019

Study Registration Dates

• First Submitted: September 4, 2023
• First Submitted That Met QC Criteria: September 11, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Plasmodium falciparum; Momordica charantia; Plasmodium vivax; primaquine; combination therapy dihydroartemisinin
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Malaria, Vivax; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Primaquine; Piperaquine; Artenimol
• Other Study ID Numbers: MCMPFPB2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: 1 year
• IPD Sharing Access Criteria: Sharing Access are only for research purposes.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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