Effect of Concomitant Mansonella Perstans Microfilaremia on Immune Responses Following Single Dose Praziquantel in People With Schistosomiasis

Effect of Concomitant Mansonella Perstans Microfilaremia on Immune Responses Following Single Dose Praziquantel in Subjects With Schistosomiasis: A Pilot Study

Background:

Schistosomiasis is a chronic infection. It is caused by parasitic worms called Schistosoma haematobium (Sh) that are spread by snails that live in rivers. It can lead to liver problems or bladder cancer. Praziquantel (PZQ) is a drug used to treat this infection. After taking it, some people develop increased resistance to reinfection with Sh. Some people with Sh infection can be infected with another worm called Mansonella perstans (Mp). Mp is spread through a biting insect called a midge. It rarely causes symptoms. However, researchers think that Mp infection could affect the body s response to PZQ treatment for or risk of reinfection with Sh.

Objective:

To find out the effects of Mp infection on the response to PZQ treatment for Sh infection.

Eligibility:

Men and women ages 14-80 who:

  • Live in Tieneguebougou, Bougoudiana, or surrounding villages in Mali
  • Are not pregnant
  • Have Sh infection
  • Have no other chronic medical conditions

Design:

  • Participants will be screened with:

    • Medical history
    • Physical exam
    • Blood and urine tests
    • Stool samples
  • Participants will be treated with a single dose of PZQ by mouth.
  • After receiving PZQ, participants will return to the clinic for blood and urine tests at the following times:

    • 4, 8, 24, 48, and 72 hours later
    • 5, 7, 9, and 14 days later
    • 1, 3, and 6 months later

Participants who are infected with Sh at the 6-month visit will get another treatment with PZQ.

...

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Chronic filarial infection is associated with downregulation of immune responses to both helminth and non-helminth antigens. Praziquantel (PZQ) treatment of schistosomiasis is associated with a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia that is correlated with resistance to reinfection. We hypothesize that chronic filarial infection with Mansonella perstans (Mp) may attenuate post-treatment eosinophilia and thus impact resistance to reinfection. To address the first part of this question, we plan to compare post-PZQ reactions and reinfection rates in 20 subjects with schistosomiasis and Mp infection to those in 20 subjects with schistosomiasis and no evidence of filarial infection in an area coendemic for both infections in Mali. Signs and symptoms, complete blood counts, intracellular and serum cytokine levels, and markers of eosinophil activation will be assessed at baseline, 4 and 8 hours, and 1, 2, 3, 5, 7, 9, and 14 days post-treatment and compared between the two treatment groups. Schistosoma haematobium reinfection rates will also be compared at 1, 3, and 6 months post-treatment.

Study Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 80 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA (SCREENING):

    1. Male or non-pregnant female subjects
    2. Age 14-80 years (per participant self-report)
    3. Resident of Tienegubougou, Bougoudiana or surrounding villages

    5. Consent to a blood draw to screen for filarial infection and a urine exam to screen for schistosomiasis

    6. Must be willing to have blood samples stored.

EXCLUSION CRITERIA (SCREENING):

  1. Known to be pregnant (by history)
  2. Chronic medical conditions, including but not limited to diabetes, renal or hepatic insufficiency, immunodeficiency, psychiatric disorder, seizure, that in the investigators judgments are deemed to be clinically significant
  3. History of hypersensitivity reaction to PZQ.
  4. Weight less than 20 kg

INCLUSION CRITERIA (INTERVENTIONAL STUDY):

  1. S. haematobium infection documented at screening and within 14 days prior to the baseline visit
  2. The subject agrees to storage of samples for study.

EXCLUSION CRITERIA (INTERVENTIONAL STUDY):

  1. Pregnancy (by urine beta-HCG)
  2. Chronic kidney or liver disease
  3. Hgb <10 mg/dL
  4. PZQ treatment since the screening visit
  5. Concomitant Schistosoma mansoni, Wuchereria bancrofti (Wb) or Onchocerca volvulus infection
  6. Use of immunosuppressive therapies, including steroids, within the past month
  7. Any condition that in the investigator s opinion places the subject at undue risk by participating in the study.

EXCLUSION OF CHILDREN AND PREGNANT WOMEN:

Pregnant women will be excluded from this study since it involves administration of medications contraindicated in pregnancy. Children less than 14 years old will be excluded because of the amount of blood required for the immunologic studies. The age of consent in Mali is 18 years of age, so children aged 14 to 17 years will sign an assent form in addition to the consent form to be signed by a parent or tutor. However, married women between the ages of 14 and 17 will sign consent as adults in view of the laws governing emancipation of women in Mali. Subjects who do not participate in this study will receive PZQ as part of the national schistosomiasis control program.

Participation of Women:

-Pregnancy: The effects of praziquantel on the developing human fetus are unknown (pregnancy category B). For this reason, females of

childbearing-age must have a negative pregnancy test result prior to receiving praziquantel. Since the half-life of praziquantel is short (3-4 hours), contraceptive measures will not be required post-treatment.

-Breast feeding: Praziquantel is known to be present in breast milk for up to 3 days following a single dose and is not approved for use in children under the age of 4 years. Consequently, women will be asked to suspend breastfeeding after treatment with PZQ for 3 days. Formula will be provided for breastfed children affected by their mother s participation during this time to ensure adequate nutrition. Depending on the age of the child, formula may be given. A pediatric nurse will be present during this time to provide assistance and counsel to the mothers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sh
Mono infected with Schistosoma haematobium
Anthelminthic
Experimental: ShMp
Coinfected with Schistosoma haematobium andMansonella perstans
Anthelminthic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Peak percentage change from baseline eosinophil count
Time Frame: During the first 7 days post-treatment
During the first 7 days post-treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Peak absolute change from the baseline eosinophil count and peakpercentage change in eosinophil granule protein levels
Time Frame: During the first 7 days post-treatment
During the first 7 days post-treatment
Frequency and severity of adverse events
Time Frame: During the first 3 days post-treatment
During the first 3 days post-treatment
Number of subjects with detectable Sh eggs in urine
Time Frame: At 1, 3 and 6 months post-treatment
At 1, 3 and 6 months post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

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Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 6, 2016

Primary Completion (Actual)

December 14, 2018

Study Completion (Actual)

December 14, 2018

Study Registration Dates

First Submitted

April 6, 2016

First Submitted That Met QC Criteria

April 6, 2016

First Posted (Estimate)

April 12, 2016

Study Record Updates

Last Update Posted (Actual)

December 17, 2019

Last Update Submitted That Met QC Criteria

December 14, 2019

Last Verified

December 14, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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