Schistosomiasis MansoniPhase 4NCT02878564
Effect of Schistosomiasis Mansoni on HIV Susceptibility and Female Genital Immunology
A Phase 4 study testing Praziquantel in people with Schistosomiasis Mansoni and HIV, run by University of Toronto at 1 site in Uganda.
Trial summary
The aim of this study is to assess the impact of Schistosoma mansoni infection and its treatment on genital immunology and HIV susceptibility in Ugandan women. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Schistosomiasis Mansoni, HIV
- What is being tested?
- Praziquantel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUganda
- Study dates
- Mar 2016to Oct 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Positive (score above "trace") on a urine CCA rapid test
- Willing to be treated with praziquantel
- Willing to give informed consent, and answer short questionnaires on economic status, and sexual risk behavior.
- Willing to comply with the requirements of the protocol
- HIV and classical STI (see below) negative
Who cannot join
- HIV infected
- Malaria infected
- Pregnant.
- Irregular menstrual cycle, or actively menstruating at the time of genital sampling.
- Tested positive for classical STIs (syphilis, gonorrhea, chlamydia, Trichomonas vaginalis) or having genital ulcers
- Prior hysterectomy
- Deemed by physician to be unlikely to complete study protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Schistosomiasis Mansoni and Its Treatment on HIV Susceptibility and Female Genital Immunology
The aim of this study is to assess the impact of Schistosoma mansoni infection and its treatment on genital immunology and HIV susceptibility in Ugandan women.
Read the detailed description
Schistosomiasis mansoni is a water-borne disease caused by helminth Schistosoma mansoni (S. mansoni), in which adult worms deposit eggs in mesenteric blood vessels. Schistomiasis prevalence in the fishing communities in East Africa, and particularly in the Lake Victoria region, exceeds 60% and there is overlap in this region with a high prevalence of HIV (29%).
A recent epidemiological study found an association between S. mansoni and HIV infection in adult women residing near Lake Victoria in Tanzania. Furthermore, in primate studies S. mansoni infection was shown to increase susceptibility to SIV infection after rectal (but not intravenous) challenge, implying that S. mansoni might increase HIV susceptibility by altering local mucosal (gut) immunology.
While S. mansoni does not directly infect the genital tract, we hypothesize that the inflammation it causes in the gut may be associated with mucosal inflammation at other sites through activation of common mucosal homing integrins such as a4b7. Therefore in this study we propose to explore whether S. mansoni increases inflammation and/or HIV susceptibility in the endocervix of adult women.
HIV-uninfected adult women from Entebbe, Uganda will be screened for schistosomiasis using a commercial CCA rapid test kit, and infected women who fulfill the study eligibility criteria will be recruited into the study. Kato-Katz microscopy analysis will be performed to assess egg shedding at baseline. Additionally, urine microscopy will be done to screen for Schistosoma hematobium (which can directly involve the genital mucosa). Schistosomiasis treatment will be provided to all participants according to Ugandan clinical guidelines.
Endocervical cytobrush, vaginal SoftCup and blood samples will be collected at three time points; at baseline and 4 and 8 weeks after schistosomiasis treatment, at the same stage of the menstrual cycle. Using an ex vivo HIV entry assay and mucosal cytokine and microbiome analyses we will quantify the effect of S. mansoni and its treatment on cervical HIV susceptibility and genital inflammation.
- Conditions
- Schistosomiasis Mansoni, HIV
- Being tested
- Praziquantel
- Keywords
- Schistosomiasis mansoni, HIV susceptibility, Genital immunology, Mucosal immunology, HIV entry assay, Adult women
- Medical subject headings
- Schistosomiasis mansoni
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PraziquantelDrug
Also called Agopraz, bromoxel, biltricide
40 mg/kg, PO (orally administered tablets)
| Study group | Role | What they receive |
|---|---|---|
| Praziquantel treatment | Experimental | Participants will be HIV-uninfected women with asymptomatic Schistosoma mansoni infection; the study will examine the impact of standard praziquantel therapy (40 mg/kg po single dose) on genital immunology and HIV susceptibility. Receives: Drug: Praziquantel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
The percentage of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
Measured: 1 month.
Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
The number of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
Measured: 1 month.
Secondary outcomes (7)
Change in the percentage of blood CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
The percentage of blood CD4+ T cells infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
Measured: 1 and 2 months.
Change in the phenotype of endocervical and blood CD4+ T cells after treatment of schistosomiasis.
Surface expression of CCR5, CD69, CD38, HLA-DR, a4b7, CCR7 and CD45RA by endocervical and blood CD4 T will be assessed using flow cytometry.
Measured: 1 and 2 months.
Change in genital proinflammatory cytokine levels after treatment of schistosomiasis.
A predefined genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines [as per Arnold K et al, Muc Immunol, 2015] will be assessed.
Measured: 1 and 2 months.
Change in the cervico-vaginal microbiome after treatment of schistosomiasis.
The cervico-vaginal microbiome will be assessed by 16s rRNA sequencing before and after schistosomiasis therapy.
Measured: 1 and 2 months.
Change in the cervico-vaginal proteome after treatment of schistosomiasis.
The genital proteome will be assessed by mass spectrometry before and after schistosomiasis therapy.
Measured: 1 and 2 months.
Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
The percentage of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
Measured: 2 months.
Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
The number of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
Measured: 2 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2016 (estimated)
- Study startMar 2016
- Primary completionOct 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Schistosomiasis MansoniStudies of the same condition, open and under way.
- More trials run by University of TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- UVRI-IAVI HIV Vaccine Program, Uganda
- Responsible party
- Principal investigator, Rupert Kaul, University of Toronto
- Investigators
- Rupert Kaul, MD/PhD, Principal investigator, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02878564
- Sponsor's protocol ID
- UT-Schisto
- Status last verified
- Oct 2016
- First submitted
- 15 Aug 2016
- Last updated
- 27 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Arnold KB, Burgener A, Birse K, Romas L, Dunphy LJ, Shahabi K, Abou M, Westmacott GR, McCorrister S, Kwatampora J, Nyanga B, Kimani J, Masson L, Liebenberg LJ, Abdool Karim SS, Passmore JA, Lauffenburger DA, Kaul R, McKinnon LR. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. 2016 Jan;9(1):194-205. doi: 10.1038/mi.2015.51. Epub 2015 Jun 24.
PubMed 26104913Downs JA, van Dam GJ, Changalucha JM, Corstjens PL, Peck RN, de Dood CJ, Bang H, Andreasen A, Kalluvya SE, van Lieshout L, Johnson WD Jr, Fitzgerald DW. Association of Schistosomiasis and HIV infection in Tanzania. Am J Trop Med Hyg. 2012 Nov;87(5):868-73. doi: 10.4269/ajtmh.2012.12-0395. Epub 2012 Oct 1.
PubMed 23033399Chenine AL, Shai-Kobiler E, Steele LN, Ong H, Augostini P, Song R, Lee SJ, Autissier P, Ruprecht RM, Secor WE. Acute Schistosoma mansoni infection increases susceptibility to systemic SHIV clade C infection in rhesus macaques after mucosal virus exposure. PLoS Negl Trop Dis. 2008 Jul 23;2(7):e265. doi: 10.1371/journal.pntd.0000265.
PubMed 18648516Joag VR, McKinnon LR, Liu J, Kidane ST, Yudin MH, Nyanga B, Kimwaki S, Besel KE, Obila JO, Huibner S, Oyugi JO, Arthos J, Anzala O, Kimani J, Ostrowski MA; Toronto HIV Research Group; Kaul R. Identification of preferential CD4+ T-cell targets for HIV infection in the cervix. Mucosal Immunol. 2016 Jan;9(1):1-12. doi: 10.1038/mi.2015.28. Epub 2015 Apr 15.
PubMed 25872482
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Schistosomiasis Mansoni and Its Treatment on HIV Susceptibility and Female Genital Immunology
- ClinicalTrials.gov ID
- NCT02878564
- Acronym / sponsor ID
- UT-Schisto
- Conditions
- Schistosomiasis Mansoni, HIV
- Keywords
- Schistosomiasis mansoni, HIV susceptibility, Genital immunology, Mucosal immunology, HIV entry assay, Adult women
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Collaborators
- UVRI-IAVI HIV Vaccine Program, Uganda
- Study start
- Mar 2016
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 25 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to assess the impact of Schistosoma mansoni infection and its treatment on genital immunology and HIV susceptibility in Ugandan women.
Detailed description
Schistosomiasis mansoni is a water-borne disease caused by helminth Schistosoma mansoni (S. mansoni), in which adult worms deposit eggs in mesenteric blood vessels. Schistomiasis prevalence in the fishing communities in East Africa, and particularly in the Lake Victoria region, exceeds 60% and there is overlap in this region with a high prevalence of HIV (29%).
A recent epidemiological study found an association between S. mansoni and HIV infection in adult women residing near Lake Victoria in Tanzania. Furthermore, in primate studies S. mansoni infection was shown to increase susceptibility to SIV infection after rectal (but not intravenous) challenge, implying that S. mansoni might increase HIV susceptibility by altering local mucosal (gut) immunology.
While S. mansoni does not directly infect the genital tract, we hypothesize that the inflammation it causes in the gut may be associated with mucosal inflammation at other sites through activation of common mucosal homing integrins such as a4b7. Therefore in this study we propose to explore whether S. mansoni increases inflammation and/or HIV susceptibility in the endocervix of adult women.
HIV-uninfected adult women from Entebbe, Uganda will be screened for schistosomiasis using a commercial CCA rapid test kit, and infected women who fulfill the study eligibility criteria will be recruited into the study. Kato-Katz microscopy analysis will be performed to assess egg shedding at baseline. Additionally, urine microscopy will be done to screen for Schistosoma hematobium (which can directly involve the genital mucosa). Schistosomiasis treatment will be provided to all participants according to Ugandan clinical guidelines.
Endocervical cytobrush, vaginal SoftCup and blood samples will be collected at three time points; at baseline and 4 and 8 weeks after schistosomiasis treatment, at the same stage of the menstrual cycle. Using an ex vivo HIV entry assay and mucosal cytokine and microbiome analyses we will quantify the effect of S. mansoni and its treatment on cervical HIV susceptibility and genital inflammation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Praziquantel treatment | Experimental | Drug: PraziquantelParticipants will be HIV-uninfected women with asymptomatic Schistosoma mansoni infection; the study will examine the impact of standard praziquantel therapy (40 mg/kg po single dose) on genital immunology and HIV susceptibility. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Positive (score above "trace") on a urine CCA rapid test
- Willing to be treated with praziquantel
- Willing to give informed consent, and answer short questionnaires on economic status, and sexual risk behavior.
- Willing to comply with the requirements of the protocol
- HIV and classical STI (see below) negative
Key exclusion criteria (7 listed)
- HIV infected
- Malaria infected
- Pregnant.
- Irregular menstrual cycle, or actively menstruating at the time of genital sampling.
- Tested positive for classical STIs (syphilis, gonorrhea, chlamydia, Trichomonas vaginalis) or having genital ulcers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PraziquantelAlso: Agopraz, bromoxel, biltricide40 mg/kg, PO (orally administered tablets) | Drug | Praziquantel treatment |
Primary outcome
Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time frame: 1 month.
The percentage of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time frame: 1 month.
The number of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
7 secondary outcomes
Change in the percentage of blood CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time frame: 1 and 2 months.
Change in the phenotype of endocervical and blood CD4+ T cells after treatment of schistosomiasis.
Time frame: 1 and 2 months.
Change in genital proinflammatory cytokine levels after treatment of schistosomiasis.
Time frame: 1 and 2 months.
Change in the cervico-vaginal microbiome after treatment of schistosomiasis.
Time frame: 1 and 2 months.
Change in the cervico-vaginal proteome after treatment of schistosomiasis.
Time frame: 1 and 2 months.
Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time frame: 2 months.
Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time frame: 2 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2016.
- Background: PubMed 26104913Arnold KB, Burgener A, Birse K, Romas L, Dunphy LJ, Shahabi K, Abou M, Westmacott GR, McCorrister S, Kwatampora J, Nyanga B, Kimani J, Masson L, Liebenberg LJ, Abdool Karim SS, Passmore JA, Lauffenburger DA, Kaul R, McKinnon LR. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. 2016 Jan;9(1):194-205. doi: 10.1038/mi.2015.51. Epub 2015 Jun 24.
- Background: PubMed 23033399Downs JA, van Dam GJ, Changalucha JM, Corstjens PL, Peck RN, de Dood CJ, Bang H, Andreasen A, Kalluvya SE, van Lieshout L, Johnson WD Jr, Fitzgerald DW. Association of Schistosomiasis and HIV infection in Tanzania. Am J Trop Med Hyg. 2012 Nov;87(5):868-73. doi: 10.4269/ajtmh.2012.12-0395. Epub 2012 Oct 1.
- Background: PubMed 18648516Chenine AL, Shai-Kobiler E, Steele LN, Ong H, Augostini P, Song R, Lee SJ, Autissier P, Ruprecht RM, Secor WE. Acute Schistosoma mansoni infection increases susceptibility to systemic SHIV clade C infection in rhesus macaques after mucosal virus exposure. PLoS Negl Trop Dis. 2008 Jul 23;2(7):e265. doi: 10.1371/journal.pntd.0000265.
- Background: PubMed 25872482Joag VR, McKinnon LR, Liu J, Kidane ST, Yudin MH, Nyanga B, Kimwaki S, Besel KE, Obila JO, Huibner S, Oyugi JO, Arthos J, Anzala O, Kimani J, Ostrowski MA; Toronto HIV Research Group; Kaul R. Identification of preferential CD4+ T-cell targets for HIV infection in the cervix. Mucosal Immunol. 2016 Jan;9(1):1-12. doi: 10.1038/mi.2015.28. Epub 2015 Apr 15.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rupert Kaul, MD/PhD principal investigator
University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Praziquantel in people with Schistosomiasis Mansoni and HIV, run by University of Toronto at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis. (time frame: 1 month.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02878564, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2016.