Treatment of Female Genital Schistosomiasis (FGS) With Praziquantel: A Proof-of-Concept Study

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Brief Title

Treatment of Female Genital Schistosomiasis (FGS) With Praziquantel: A Proof-of-Concept Study

Official Title

Treatment of Female Genital Schistosomiasis (FGS) With Praziquantel: A Proof-of-Concept Study

Brief Summary

      Female genital schistosomiasis (FGS) is a frequent manifestation of the infection with
      Schistosoma haematobium or mansoni. FGS is probably the most neglected gynaecological
      condition in the tropics.

      Inflammation of genital tissue persists as long as adult worms are present in the
      circulation, and new eggs are released. Hence, lesions can only heal if the inflammation is
      abated and a normal immune response is restored

      A randomized controlled study will be carried out to compare the efficacy of the standard
      treatment with that of five repeated doses of praziquantel.

      Outcome measure is the disappearance/regression of clinical pathology at the cervix, in the
      vagina/vulva.
    

Detailed Description

      Female genital schistosomiasis (FGS) is a frequent manifestation of the infection with
      Schistosoma haematobium or mansoni. It occurs in women of all age groups, including young
      girls and is associated with important, frequently debilitating and stigmatizing morbidity.
      It may develop into a life-threatening condition. FGS is probably the most neglected
      gynaecological condition in the tropics.

      Depending on where eggs are released the clinical pathology develops in vulva and vagina,
      cervix, uterus, Fallopian tubes and the ovaries. All genital organs may be affected
      simultaneously. Women with FGS report spontaneous, or post-coital bleeding, vaginal
      discharge, pain during sexual intercourse, pelvic pain, irregular menstruation and
      infertility. Vaginal discharge and itching, pain during sexual intercourse, spontaneous +
      post-coital bleeding, as well as menstruation abnormalities are attributed by the women to
      STIs. This results in shame, mental strain and distress, eventually causes stigmatization and
      social exclusion leading to an impaired life quality.

      Clinical, histopathological, immunological and epidemiological evidence suggests that there
      is a cause-effect relationship between FGS and HIV infection. There are hints of a cause
      effect relationship between FGS and HPV. The association of FGS with HIV /HPV infection
      underlines the pivotal importance for an effective treatment of FGS.

      Clinical pathology is the result of a complex inflammatory response to antigens released by
      adult worms and viable eggs. The inflammation of genital tissue persists as long as adult
      worms are present in the circulation, and new eggs are released and become trapped. Hence,
      lesions can only heal if the inflammation is abated and a normal immune response is restored.
      This means that all worms have to be eliminated and reinfection has to be prevented for some
      time to allow complete healing of genital organs.

      Based on this rationale, five doses of praziquantel will be given over a period of 10 weeks
      to ensure that all existing worms will be eliminated. The first three doses aim to kill all
      adult worms. The fourth dose will kill schistosomula which will mature in the following
      weeks. The last dose will prevent women from re-infection.

      A randomized controlled study will be carried out to compare the efficacy of the standard
      treatment with that of repeated doses of praziquantel. Since a placebo is not available, the
      study will not be blinded. Outcome measure is the disappearance/regression of clinical
      pathology at the cervix, in the vagina/vulva.

      The result of this study has important implications for the sexual health of millions of
      women in sub-Saharan Africa.

      The aim of the study is to compare standard treatment of schistosomiasis as recommended by
      WHO (a single dose of praziquantel 40 mg/kg)- with a treatment based on a new rationale: five
      doses of praziquantel 40 mg/kg

        -  1 x 40 mg/kg after enrollment in the study (D1, H0) plus two single doses (40 mg/kg)
           after 12 and 24 hours after the first treatment

        -  1 x 40 mg/kg five weeks following the 1st PZQ treatment

        -  1 x 40 mg/kg ten weeks following the 1st PZQ treatment
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

Pathognomonic sign(s) in the cervix

Secondary Outcome

 Gynaecological complaint score

Condition

Schistosomiasis

Intervention

Praziquantel 600Mg Oral Tablet x 5

Study Arms / Comparison Groups

 A - Single dose og PZQ
Description:  Single dose of Praziquantel 40 mg/kg Standard treatment of schistosomiasis as recommended by WHO

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

116

Start Date

September 3, 2019

Completion Date

February 21, 2020

Primary Completion Date

February 21, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  Women 15 to 35 years of age with a gynaecological/urinary/lower abdominal complaint

          -  The woman has signed the informed consent form (IFC); in the case of minors, the IFC
             has to be signed by parent or guardian.

          -  The woman does not plan to leave the area within 6 months and accept to come to the
             CSB regularly following the scheduled follow-up (at week 5,10 and 15).

          -  The woman with confirmed diagnosed of FGS (as described in section 6.3.1)

          -  The woman agrees to be examined clinically and gynaecologically including taking
             specimens from the genital tract (collection of vaginal lavage fluid, collection of
             cells with a cytobrush).

          -  The woman agrees to provide a urine and a stool sample.

          -  The woman agrees that a venous blood sample for laboratory assessments is taken.

          -  The woman accepts to stay at the hospital for 2 days follow-up after the first dose of
             PZQ.

        Exclusion Criteria:

          -  Virgin (assessed by gynaecologist)

          -  Pregnancy (determined by pregnancy test)

          -  Tumor of vulva, vagina, uterus (diagnosed by gynaecologist)

          -  Treatment with praziquantel during the last 3 months

          -  Hysterectomy

          -  Known HIV positive prior to enrollment

          -  Any severe medical condition requiring hospitalization

          -  The woman is unable to comprehend the nature and objectives of the study

          -  The woman is judged by the investigators to be unlikely to participate regularly in
             the follow-up

          -  The woman is taking any drug that might affect the metabolism of PZQ and that is
             contraindicated the last two weeks before the enrollment. These drugs are as follows:
             rifampin; phenytoin, carbamazepine, phenobarbital; dexamethasone;

          -  The woman is taking a drug which decreases the activity of praziquantel metabolizing
             enzymes (P450 inhibitors) the last two weeks before the enrollment, for example
             cimetidine, ketoconazole, itraconazole, erythromycin.

          -  All contraindications to Praziquantel
      

Gender

Female

Ages

15 Years - 35 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Peter Leutscher, PhD, , 

Location Countries

Madagascar

Location Countries

Madagascar

Administrative Informations


NCT ID

NCT04115072

Organization ID

RHN_PCL_01


Responsible Party

Sponsor

Study Sponsor

Vendsyssel Hospital

Collaborators

 Charite University, Berlin, Germany

Study Sponsor

Peter Leutscher, PhD, Study Director, Centre for Clinical Research, North Denmark Regional Hospital, Denmark


Verification Date

May 2020