Treatment of Female Genital Schistosomiasis (FGS) With Praziquantel: A Proof-of-Concept Study
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|ClinicalTrials.gov Identifier: NCT04115072|
Recruitment Status : Completed
First Posted : October 3, 2019
Last Update Posted : May 18, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Schistosomiasis||Drug: Praziquantel 600Mg Oral Tablet x 5 Drug: Praziquantel 600Mg Oral Tablet x 1||Phase 2 Phase 3|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||116 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment of Female Genital Schistosomiasis (FGS) With Praziquantel: A Proof-of-Concept Study|
|Actual Study Start Date :||September 3, 2019|
|Actual Primary Completion Date :||February 21, 2020|
|Actual Study Completion Date :||February 21, 2020|
Active Comparator: A - Single dose og PZQ
Single dose of Praziquantel 40 mg/kg Standard treatment of schistosomiasis as recommended by WHO
Drug: Praziquantel 600Mg Oral Tablet x 1
Single dose of Praziquantel 40 mg/kg
Other Name: PZQ
Experimental: B - Five doses of PZQ
Five doses of Praziquantel
1 x 40 mg/kg Praziquantel after enrollment in the study plus two single doses (40 mg/kg) after 12 and 24 hours after the first treatment
1 x 40 mg/kg Praziquantel five weeks following the 1st dose
1 x 40 mg/kg Praziquantel ten weeks following the 1st dose
Drug: Praziquantel 600Mg Oral Tablet x 5
Five doses of Praziquantel 40 mg/kg
Other Name: PZQ
- Pathognomonic sign(s) in the cervix [ Time Frame: 15 weeks ]Changes is quantitatively measured by the comparison of the number of sectors of the cervix affected by a pathognomonic sign before treatment and at the end of the study.
- Gynaecological complaint score [ Time Frame: 15 weeks ]Gynaecologial symptoms assessed by a questionnaire (Lower abdominal pain, Itching of vagina/vulva, Vaginal discharge with a strange odor, Pain/abnormal sensation during sexual intercourse, Bleeding after sexual intercourse, Abnormal sensation when touching vulva/vagina, Spontaneous bleeding (outside menstruation), Irregular menstruation, Infertility (primary or secondary) after two years without contraception, Pain during micturition, Blood in urine outside menstruation).
- Vaginal Schistosome DNA [ Time Frame: 15 weeks ]Concentration of schistosome DNA in vaginal fluid
- Vaginal Pro-inflammatory Th2-dependent cytokines /chemokines [ Time Frame: 15 weeks ]Concentration of selected pro-inflammatory Th2-dependent cytokines /chemokines in vaginal fluid
- Vaginal ECP [ Time Frame: 15 weeks ]Eosinophilic cationic protein (ECP) in vaginal lavage fluid
- Cytobrush Schistosome DNA [ Time Frame: 15 weeks ]Concentration of schistosome DNA in cytobrush material from vagina
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04115072
|Ambanja, Diana, Madagascar, 203|
|Study Director:||Peter Leutscher, PhD||Centre for Clinical Research, North Denmark Regional Hospital, Denmark|
|Principal Investigator:||Bodo S Randrianasolo, MD||K'OLO VANONA; Antananarivo, Madagascar|