Momordica Charantia and Dihydroartemisinin-piperaquined-primaquine for Uncomplicated Plasmodium Falciparum Malaria Patients in Southwest Sumba Regency (MCHUPF)

Effectiveness of Momordica Charantia Extract Compared to the Standard Antimalarial Drug Combination Dihydroartemisinin Piperaquine-primaquine in Patients With Uncomplicated Falciparum Malaria, in Sumba Barat Daya District of Indonesia

Currently, the first-line combination of artemisinin, piperaquine and prima-quine is quite effective in controlling malaria, however, the threat of spread of drug-resistant parasites has been reported. A study is conducted to assess the efficacy and safety extract of bitter melon (Momordica charantia/MC) regimens compared to the combination of dihydroartemisinin piperaquine primaquine (DHP+PQ) on the sexual and asexual stage of P. Falciparum uncomplicated in Sumba Barat Daya District, Indonesia

Study Overview

• Status: Completed
• Conditions: Uncomplicated Plasmodium Falciparum
• Intervention / Treatment: Drug: Dihydroartemisinin; Drug: Piperaquine; Drug: Primaquine; Drug: Momordica Charantia Extract

Detailed Description

The Study was conducted in Kori Primary Health Cender, Sumba Barat Daya District, East Nusa Tenggara Province on Sumba Island.

The study subject received either 3 day of dihydroartemisinin-piperaquine and primaquine 1 day on first day (DHP+PQ) or extract of bitter melon (Momordica charantia/MC) + Placebo 1 day on first day according to their body weight.

Patients with fever or history of fever within the past 24 hours were screened by microscopic examination of giemsa stained tihick blood films to detect Plasmodium falciparum infection.

All Patient were allocated by single blind randomization to receive DHP (on day 0 to day 2)+PQ (on day 0 only) or extract of bitter melon (Momordica charantia/MC) (on day 0 to day 2)+placebo (on day 0 only). The procedures of drug administration in the study were as follows:

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Indonesia
  • East Nusa Tenggara
    • Tambolaka, East Nusa Tenggara, Indonesia, 87255
      • Kori Puskesmas

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:-

1. Age ≥ 18 years old male or female up to 60 years old
2. Single Plasmodium falciparum infection based on microscopic examination.
3. Count the parasites for Plasmodium falciparum at least 2 large visual field asexual parasites (LPB) by examining 15 LPB
4. Density of parasites 1000-100,000/micro liter
5. Has no history of uncontrolled comorbidities
6. History of fever in the last 24 hours for falciparum malaria
7. Not taking other antimalarial drugs in the last 2 weeks.
8. Have no previous history of malaria.
9. Willing to come to the health facility according to the specified follow-up schedule.
10. Willing to participate in research and established procedures.
11. There is no history of allergy to antimalarial drugs.

Exclusion Criteria:

1. Signs of general weakness, or decreased consciousness or recurrent seizures or circulation failure or pulmonary edema or signs of anemia or yellow body and slightly red urine.
2. If the examination results show mixed Plasmodium and non-Plasmodium falciparum.
3. Has a history of severe liver, kidney and heart dysfunction, bradycardia and heart rhythm disturbances.
4. Does not control regularly according to the research schedule
5. Pregnant and lactating women
6. There are signs of severe malaria
7. Patients with chronic diseases, for example: heart, kidney, liver, HIV.
8. Mixed infection.

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: Dihydro artemisinin Piperakuin (Fixed Dose Combination) and Primaquine; Fixed Dose Combination content in the form of 40 mg dihydroartemisinin and 320 mg piperaquine administered for 3 days with a dose of dihydroartemisinin 2-4 mg/Kg body weight, piperaquine at a dose of 16-32 mg/Kg body weight in the form of a combination set out in the table based on body weight and age. Primaquine dose of 0.25 mg/Kg body weight is given only on the first day. Dihydroartemisinin-piperaquine was local product by PT Mersi Pharmaceuticals, batch No 220610, produced on Jun/22 and expiring on Jun/24. primaquine was local product by PT Phapros Indonesia, Batch No 56386001, produced on Jan/22 and expiring date jan/25.	Drug: Dihydroartemisinin; dihidroartemisinin dose of 2-4 mg/Kg Body weight taken for 3 days; Other Names: 1st group; Drug: Piperaquine; piperaquine at a dose of 16-32 mg/Kg body weight taken for 3 days; Other Names: 1st group; Drug: Primaquine; Primaquine dose 0.25 mg/kg body weight given to uncomplicated Plasmodium falciparum patients on the first day only; Other Names: 1st Group
Experimental: Extract Capsul Momordica Charantia; Momordica Charantia 325 mg in 500 mg capsules is given to patients with uncomplicated plasmodium falsiparum malaria as one capsule per day for three days for body weight less than 60 kg. Patients with a body weight of more than 60 kg are given two capsules per day for three days.	Drug: Momordica Charantia Extract; Momordica charantia extract capsules at a dose of 325 mg were given to patients for 3 days; Other Names: 2nd group

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	28 day post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parasite clearence times	parasite reduction ratio	28-days
Fever clearence time	time taken for the axilla temperature to fall below 37.5°C in patients who were febrile at inclusion	28 days
Number of adverse event		28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure imunomodulator Effect	Measuring the immunomodulatory effect by measuring the levels of TNF alpha and interferon gamma cytokines before and after the treatment intervention 1 x 24 hours	1x24 hour before and after treatment

Collaborators and Investigators

• Sponsor: Syamsudin Abdillah,Ph.D, Pharm D
• Collaborators: Apt. Dian Yudianto; Dr. dr Erni J. Nelwan, Sp.PD, Ph.D; Apt.Hesty Utami Ramadaniati, M.Clin, Pharm, Ph.D

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.
• Sutanto I, Suprijanto S, Kosasih A, Dahlan MS, Syafruddin D, Kusriastuti R, Hawley WA, Lobo NF, Ter Kuile FO. The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South sumatra, Western indonesia: an open-label, randomized, controlled trial. Clin Infect Dis. 2013 Mar;56(5):685-93. doi: 10.1093/cid/cis959. Epub 2012 Nov 21.
• 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): November 1, 2022
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 13, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Parasite number, clinical symtomps, immunomodulator
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Primaquine; Piperaquine; Artenimol
• Other Study ID Numbers: B-056/FI2/KEPK/TL.00/10/2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No