A Phase 2/3 interventional study of Praziquantel 40 mg/kg per dose given once annually and Praziquantel 40 mg/kg given three times per year in Schistosomiasis, Schistosoma Mansoni and Liver Fibrosis, sponsored by Rhode Island Hospital. Not yet recruiting at 1 site in Uganda. Open to participants aged 15 Years to 40 Years. Per ClinicalTrials.gov, last updated 2026-08-12.
Sponsored by Rhode Island Hospital · Phase 2/3, Interventional, and Treatment
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:
Participants will:
Be screened for schistosomiasis using a urine test If participants have schistosomiasis they will undergo other screening procedures including a liver ultrasound, blood tests, and a physical exam if they have both schistosomiasis and liver (fibrosis) they will be invited to participate in the trial
If they are in the trial they will:
Take the drug praziquantel once per year or three times per year based on randomization for three years Have a liver ultrasound and blood samples for markers of liver fibrosis once per year Provide a urine sample to test for schistosomiasis each year
The overarching goals of this proposal are to conduct a double blind, randomized controlled trial (RCT) (Phase III) among N=600 participants ages 15-40 in Lake Albert, Uganda, that will examine varying frequencies of treatment with Praziquantel (standard 40 mg/kg PO every 4 months or annually for three years) to identify approaches that best reverse or halt fibrosis as captured by ultrasound annually.
After excluding other causes of hepatic fibrosis, the trial will randomize/enroll N = 600 participants for the RCT (N = 150 individuals in each age and sex strata (4 sub-groups)) who have compensated schistosomal liver fibrosis based on the WHO "Niamey" ultrasound protocol for S. mansoni.
Using stratified randomization by subgroup treatment arms are as follows:
Randomization and blinding The trial statistician will generate randomization codes by study number in blocks for each age/sex group and share with the pharmacist. Because the placebo and praziquantel tablets will be matched, allocation to a given study arm will be concealed to participants and study staff, including ultra-sonographers who are assessing study outcomes.
The overall goals of this trial are to examine varying frequencies of treatment with Praziquantel (every 4 months or annually for three years) to identify approaches that best reverse or halt fibrosis as captured by ultrasound annually. Investigators will also identify novel biomarkers using our multiplexed assay which captures over 40 analytes involved in fibro-degradation and fibro-proliferation, which best predict progression of fibrosis.
The primary objective for the trial will be to assess the impact of PZQ dosed annually vs every 4 months over three years on grade of fibrosis as captured by the Niamey protocol from baseline to three years with ultrasound performed annually. The primary endpoint is improvement in grade of fibrosis (any improvement) during this three-year period of follow up. Grades by image pattern are below and improvement, stability or worsening is based on changes in these categories from baseline.
Secondary objectives are to:
The primary outcome will be any improvement in grade of fibrosis (mild, moderate, severe) from baseline to study close out at three years dichotomized as Yes/No improvement to produce a rate of improvement across study arms.
Hepatic Fibrosis Grade: Investigators will employ the "Niamey" protocol, for the assessment of fibrosis in the context of S. mansoni. Hepatosplenic schistosomiasis (HSS) encompasses a characteristic type of portal fibrosis, also called Symmer's clay pipe fibrosis or periportal fibrosis, and its resulting complications such as portal hypertension. The Niamey protocol has a detailed scoring system for fibrosis that is based on both "image pattern" and degree of periportal fibrosis. For S. mansoni, fibrosis is characterized by grades (B- F) with grades C to F constituting mild to severe grades of fibrosis.
Since image pattern B is not specific to schistosomiasis, individuals with pattern B will not be included. Fibrosis will be graded with respect to location (periphery (C) \& central (D, E, F)). These scores culminate in a severity grading that maps to mild, moderate, and severe.
Mild: Image Pattern C Moderate: Image Pattern D Severe: Image pattern E or F
Improvement is defined as change from baseline status as follows:
Progression is defined as change in baseline status as follows:
Clinical secondary outcomes include change in grade of portal hypertension from baseline.
Portal Hypertension: We will separately assess whether there is evidence of significant portal hypertension by ultrasound as per the Niamey protocol. The presence of portal hypertension will be defined by the portal vein quotient (adjusted for height). A quotient greater than 7.5 is indicative of portal hypertension. It's severity is assessed as absent, dilated or severely dilated (Normal: ≤ 7.5 mm/m, Dilated: 7.6 - 10 mm/m, Severely dilated: > 10 mm/m)
Secondary outcomes include:
Investigators will also address the following exploratory objectives which do not represent clinical endpoints for the trial but rather identify key fibrosis biomarkers that predict the presence of hepatic fibrosis and its progression from baseline. These secondary/exploratory outcomes will use the aforementioned definition of change in fibrosis grade from baseline.
At baseline, investigators will cross-sectionally evaluate fibrosis biomarkers with a multiplexed assay "FibroPlex" (e.g microRNAs, hyaluronic acid) with over 40 analytes using Area Under the Curve Analyses to identify specific biomarkers and "cut offs" which accurately identify individuals with varying stages of liver fibrosis by ultrasound. Investigators will then longitudinally evaluate fibrosis biomarkers that identify risk of progression from mild-moderate to higher grades of fibrosis as assessed by ultrasound annually stratified by treatment allocation among the N=600 RCT participants. This will allow identification of individuals at greatest risk of fibrosis progression before overt symptoms and while still reversible.
79 studies on the registry are indexed under Schistosomiasis; 14 are open to participants now.
This study's planned enrollment of 600 is above the median of 289 across 52 interventional studies indexed under Schistosomiasis.
Browse Schistosomiasis studies →Rhode Island Hospital is the lead sponsor of 191 studies on the registry; 36 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 2 (17%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 (enhanced frequency)
Drug: Praziquantel 40 mg/kg given three times per year
Drug page: Praziquantel
Standard recommended by World Health Organization (annual treatment)
Drug page: Praziquantel
This intervention provides Praziquantel treatment three times per year (enhanced frequency compared to current WHO guidelines)
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.
Time frame: three years
Improvement in Severity of Portal Hypertension
We will assess whether there is evidence of significant portal hypertension by ultrasound as per the Niamey protocol at baseline and annually. The presence of portal hypertension will be defined by the portal vein quotient (adjusted for height). A quotient greater than 7.5 is indicative of portal hypertension. The severity is graded based on the portal vein quotient as absent, dilated or severely dilated. This secondary outcome improvement in severity of portal hypertension that was present at baseline by the three year close out.
Time frame: Three years
Improvement in grade of liver fibrosis from baseline to two years
improvement in grade of liver fibrosis after two years
Time frame: Two years
Improvement in severity of portal hypertension after two years
Improvement in severity of portal hypertension (absent, dilated or severely dilated) as assessed by ultrasound from baseline to two years
Time frame: Two years
Improvement in grade of liver fibrosis at one year
Improvement in grade of liver fibrosis as assessed by ultrasound from baseline to one year
Time frame: one year
Improvement in severity of portal hypertension after one year
Improvement in severity of portal hypertension (absent, dilated or severely dilated) as assessed by ultrasound from baseline to one year
Time frame: one year
Plan to share: Yes — The types of data that we expect to be generated include demographic clinical and laboratory as follows: Demographic and socioeconomic status date Urine results for point of care test to diagnosis schistosomiasis (Circulating Cathodic Antigen) Ultrasound of liver and spleen Hematology indices - Complete blood count Chemistry indices to include renal function (BUN, Cr) and liver function (GGT, ALT, AST, total bilirubin) Reactogenicity following praziquantel treatment Fibrosis biomarkers (about 38 analytes capturing fibrogeneration and fibroproliferation.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, 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: Expanded Special Project for Elimination of NTDs (ESPEN) EuPathDB- a database for genomic and bioinformatic analyses. https://www.sanger.ac.uk/collaboration/eupathdb/ WormBase ParaSite- a database for genomic and bioinformatic analyses on helminths including schistosomes. https://parasite.wormbase.org/index.html 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
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Praziquantel