Different Treatment Frequencies for Hepatic Fibrosis Due to Schistosomiasis: an RCT

NCT07754617 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 25-0026R01AI184979
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if treating individuals living in Uganda who have liver fibrosis (scarring) due to schistosomiasis would benefit from more frequent treatment with drug praziquantel. This drug is already approved to treat schistosomiasis and is used globally. The study will include individuals who have schistosomiasis and some degree of liver fibrosis. The main questions it aims to answer are:

1. 1.Does treating people three times per year as compared to once per year as currently recommended improve the likelihood the hepatic fibrosis will improve over three years.
2. 2.Does treating people three times per year as compared to once per year as currently recommended decrease the risk they have for bleeding due to portal hypertension over three years.
3. 3.Is there a blood test that can tell us which people will experience worsening liver fibrosis before this happens.

Conditions

Schistosomiasis; Schistosoma Mansoni; Liver Fibrosis; Portal Hypertension

Keywords

schistosomiasis; schistosome mansoni; hepatic fibrosis; liver fibrosis; portal hypertension

Outcome Measures

Primary Outcomes (1)

• Improvement in liver fibrosis grade

  The primary outcome will be any improvement in grade of fibrosis (mild, moderate, severe) from baseline to study close out at three years.

  three years

Secondary Outcomes (5)

• Improvement in Severity of Portal Hypertension

  Three years

• Improvement in grade of liver fibrosis from baseline to two years

  Two years

• Improvement in severity of portal hypertension after two years

  Two years

• Improvement in grade of liver fibrosis at one year

  one year

• Improvement in severity of portal hypertension after one year

  one year

Study Arms (2)

Annual treatment (standard) with Praziquantel

OTHER

Treatment with praziquantel once per year (standard recommendation)

Drug: Praziquantel 40 mg/kg per dose given once annually

Treatment with Praziquantel three times per year

EXPERIMENTAL

Treatment with praziquantel three times per year (enhanced frequency)

Drug: Praziquantel 40 mg/kg given three times per year

Interventions

Praziquantel 40 mg/kg per dose given once annually DRUG

Standard recommended by World Health Organization (annual treatment)

Annual treatment (standard) with Praziquantel

Praziquantel 40 mg/kg given three times per year DRUG

This intervention provides Praziquantel treatment three times per year (enhanced frequency compared to current WHO guidelines)

Treatment with Praziquantel three times per year

Eligibility Criteria

• Age: 15 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• S. mansoni infection as determined by urine Circulating Cathodic Antigen (CCA)
• Otherwise healthy as determined by history and physical examination conducted by the study clinician
• Not Pregnant
• Age 15-40 years
• Consent for individuals 18 years of age and older, and parental consent and adolescent assent for participants ages 15-17 years.
• The presence of hepatic fibrosis due to S. mansoni (Niamey protocol grade C-F) and compensated (without late-stage portal hypertension) after ruling out other causes of hepatic fibrosis as below.

You may not qualify if:

• History of upper gastrointestinal bleeding
• Hepatic fibrosis that is not deemed to be due to schistosomiasis based on ultrasound and hepatitis serologies. For example, alcoholic cirrhosis or presence of chronic Hepatitis B or C by point of care test
• Known neurocysticercosis or ocular cysticercosis

Sponsors & Collaborators

• Rhode Island Hospital: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator

Study Sites (1)

Uganda Virus Research Institute

Entebbe, Uganda

Location

Related Publications (8)

• King CH, Binder S, Shen Y, Whalen CC, Campbell CH, Wiegand RE, Olsen A, Secor WE, Montgomery SP, Musuva R, Mwinzi PNM, Magnussen P, Kinung'hi S, Andrade GN, Ezeamama AE, Colley DG. SCORE Studies on the Impact of Drug Treatment on Morbidity due to Schistosoma mansoni and Schistosoma haematobium Infection. Am J Trop Med Hyg. 2020 Jul;103(1_Suppl):30-35. doi: 10.4269/ajtmh.19-0830.

  PMID: 32400348 BACKGROUND

• Tamarozzi F, Fittipaldo VA, Orth HM, Richter J, Buonfrate D, Riccardi N, Gobbi FG. Diagnosis and clinical management of hepatosplenic schistosomiasis: A scoping review of the literature. PLoS Negl Trop Dis. 2021 Mar 25;15(3):e0009191. doi: 10.1371/journal.pntd.0009191. eCollection 2021 Mar.

  PMID: 33764979 BACKGROUND

• Gunda DW, Kilonzo SB, Manyiri PM, Peck RN, Mazigo HD. Morbidity and Mortality Due to Schistosoma mansoni Related Periportal Fibrosis: Could Early Diagnosis of Varices Improve the Outcome Following Available Treatment Modalities in Sub Saharan Africa? A Scoping Review. Trop Med Infect Dis. 2020 Feb 3;5(1):20. doi: 10.3390/tropicalmed5010020.

  PMID: 32028581 BACKGROUND

• Andrade G, Bertsch DJ, Gazzinelli A, King CH. Decline in infection-related morbidities following drug-mediated reductions in the intensity of Schistosoma infection: A systematic review and meta-analysis. PLoS Negl Trop Dis. 2017 Feb 17;11(2):e0005372. doi: 10.1371/journal.pntd.0005372. eCollection 2017 Feb.

  PMID: 28212414 BACKGROUND

• Shen Y, Wiegand RE, Olsen A, King CH, Kittur N, Binder S, Zhang F, Whalen CC, Secor WE, Montgomery SP, Mwinzi PNM, Magnussen P, Kinung'hi S, Campbell CH, Colley DG. Five-Year Impact of Different Multi-Year Mass Drug Administration Strategies on Childhood Schistosoma mansoni-Associated Morbidity: A Combined Analysis from the Schistosomiasis Consortium for Operational Research and Evaluation Cohort Studies in the Lake Victoria Regions of Kenya and Tanzania. Am J Trop Med Hyg. 2019 Dec;101(6):1336-1344. doi: 10.4269/ajtmh.19-0273.

  PMID: 31407653 BACKGROUND

• Pach S, Webb EL, Edielu A, Nagawa R, Anguajibi V, Mpooya S, Wu H, Colt S, Mawa P, Richter J, Friedman JF, Bustinduy AL. Baseline Liver Ultrasound Findings in Preschool Children From the Praziquantel in Preschoolers Trial in Lake Albert, Uganda. Pediatr Infect Dis J. 2024 Jan 1;43(1):14-20. doi: 10.1097/INF.0000000000004119. Epub 2023 Oct 30.

  PMID: 37922490 BACKGROUND

• LoVerde PT. Schistosomiasis. Adv Exp Med Biol. 2019;1154:45-70. doi: 10.1007/978-3-030-18616-6_3.

  PMID: 31297759 BACKGROUND

• GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep 16;390(10100):1211-1259. doi: 10.1016/S0140-6736(17)32154-2.

  PMID: 28919117 BACKGROUND

MeSH Terms

Conditions

Schistosomiasis; Liver Cirrhosis; Hypertension, Portal

Interventions

Praziquantel

Condition Hierarchy (Ancestors)

Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Vector Borne Diseases; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Jennifer F Friedman, MD, PhD

CONTACT

401 444 7990; jennifer_Friedman@Brown.edu

Haiwei W Wu, MD, PhD

CONTACT

401 444 7339; Haiwei_wu@Brown.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for International Health Research & Professor of Pediatrics

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: November 2029 through November 2034
• Access Criteria: Repository where scientific data and metadata will be archived: We provide examples of data repositories we believe will be relevant for this proposal. In addition, the trial will be registered at Clinicaltrials.gov. Repositories currently used or anticipated include, but are not limited to: 1. Expanded Special Project for Elimination of NTDs (ESPEN) 2. EuPathDB- a database for genomic and bioinformatic analyses. https://www.sanger.ac.uk/collaboration/eupathdb/ 3. WormBase ParaSite- a database for genomic and bioinformatic analyses on helminths including schistosomes. https://parasite.wormbase.org/index.html 4. BEI Resources- a repository for parasite strains, plasmids, cDNA libraries, monoclonal antibodies and genomic tools related to malaria, schistosomes, trypanosomes, TB, and other parasitic agents. https://www.beiresources.org/Home.aspx

Locations

UG (1)