Intestinal HelminthiasisPhase 4NCT02597556
The Impact of Anthelmintic Treatment on the Incidence of Diarrheal Disease in Vietnamese School Children
A Phase 4 study testing Albendazole in people with Intestinal Helminthiasis and Diarrhea, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.
Trial summary
Cheap and effective drugs called 'anthelmintics' are routinely administered to children in developing countries to eliminate infections by parasitic helminths. However, the effects of anthelmintic treatment on other pathogens (e.g., bacteria, viruses, protozoa) remain unknown. Read more about this study
- Who is it for?
- Ages 6 to 15 yearsHealthy volunteers can take part
- Conditions the study is for
- Intestinal Helminthiasis, Diarrhea
- What is being tested?
- Albendazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteVietnam
- Study dates
- Feb 2016to May 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 6 to 15 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Between 6-15 years of age
- Written informed consent from a parent or guardian
- Written assent from children >10 years of age
Who cannot join
- Subjects who do not fulfill any component of the inclusion criteria
- Subjects that are both hookworm-positive and anemic, as defined by the WHO guidelines
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Impact of Anthelmintic Treatment on the Incidence of Diarrheal Disease in School Children in Southern Vietnam
Cheap and effective drugs called 'anthelmintics' are routinely administered to children in developing countries to eliminate infections by parasitic helminths. However, the effects of anthelmintic treatment on other pathogens (e.g., bacteria, viruses, protozoa) remain unknown. The aim of this study is to investigate the impact of anthelmintic treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam. Diarrheal disease remains a substantial cause of morbidity and mortality in children in Vietnam, and these children are typically co-infected with intestinal helminths. As helminths and diarrheal pathogens infect the same intestinal niche, anthelmintic treatments may alter host immune responses and the composition of the gut microbiota in ways that affect infection and disease risks caused by diarrheal pathogens.
This study will recruit 350 helminth-infected and 350 helminth-uninfected children aged 6-15 years. Recruited children will be randomized to receive either anthelmintic or placebo treatment once every three months and will be monitored for incidences of diarrheal disease for 12 months. At the 12-month time point, all children will receive anthelmintic treatment. Blood and stool samples will be collected throughout the study and used for evaluation of anemia and host immune responses, and for classification of gut microbes and parasite detection, respectively. The interventional study proposed here will provide an important first test of whether anthelmintic treatments have any indirect effects on infections caused by diarrheal pathogens.
Read the detailed description
This study is a randomized, double-blind, placebo-controlled trial to evaluate the effects of 400 mg albendazole treatment against placebo on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. Children will be enrolled from three primary schools in Cu Chi district in Ho Chi Minh City, Vietnam. Children will be screened for infections by the four most common soil-transmitted helminths, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, and Ancylostoma duodenale. Infected and uninfected individuals will be recruited into the study and randomized to either receive albendazole treatment once every three months for 12 months, or to placebo once every three months for 9 months, after which albendazole treatment will be given at month 12, in accordance with the current deworming schedule in Cu Chi district. A questionnaire regarding the participant's demographics, his/her daily habits, and potential sources of infection will be administered at baseline. Weekly active and passive surveillance of diarrheal cases will be conducted throughout the study, and a health questionnaire will be administered during all cases of diarrhea and at the end of the study.
- Conditions
- Intestinal Helminthiasis, Diarrhea
- Being tested
- Albendazole, Placebo
- Keywords
- Albendazole, Ancylostoma duodenale, Ascariasis lumbricoides, Coinfection, Diarrhea, Helminths, Necator americanus, Microbiota, Trichuris trichiura
- Medical subject headings
- Intestinal helminthiasis, Diarrhea, Coinfection, Trichuriasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlbendazoleDrug
A single 400mg dose of Albendazole administered at 0, 3, 6, 9, and 12 months.
PlaceboDrug
Matching placebo tablet administered at 0, 3, 6, and 9 months. At month 12, all participants will receive a single dose of 400mg Albendazole.
| Study group | Role | What they receive |
|---|---|---|
| Albendazole | Active comparator | Albendazole will be administered as a single 400mg chewable tablet at 0, 3, 6, 9, and 12 months. Receives: Drug: Albendazole |
| Placebo | Placebo comparator | Matching Placebo will be administered as a single chewable tablet at 0, 3, 6, and 9 months. At month 12, all participants will receive a single 400mg Albendazole tablet. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance
Incidence of diarrhea will be defined according to WHO guidelines as three or more loose stools in a 24-hour period or at least one bloody/mucoid stool. To be considered a new episode of diarrhea, at least three intervening days of normal stools without other gastrointestinal symptoms need to have passed between diarrhea occurrences.
Measured: 12 months
Secondary outcomes (6)
Prevalence and intensity of soil-transmitted helminth infections by real-time PCR and microscopy
Measured: Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases
Prevalence and intensity of enteric viruses and bacteria that cause diarrhea assessed by real-time PCR and the Luminex xTAG Gastrointestinal Pathogen Panel
Measured: Time Frame: Baseline, 3, 6, 9, and 12 months, and during and two weeks after diarrhea cases
Changes in fecal microbiota composition by Illumina sequencing
Measured: Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases
Changes in blood cytokine (Th1, Th2, TH17, and Treg) levels by bead-based immunoassays
Measured: Baseline, 6, and 12 months of study
Antibody isotype response to helminth and diarrheal antigens by ELISA
Measured: Baseline, 6, and 12 months
Mean z-scores (height-for-age, weight-for-age, weight-for-height)
Measured: Baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2015 (estimated)
- Study startFeb 2016
- Primary completionMay 2016
- Study completionMay 2016
Why it stopped: The prevalence of worm infections in the site is significantly lower than expected
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Intestinal HelminthiasisStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oxford University Clinical Research Unit, Vietnam
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Ho Chi Minh Preventive Medicine Centre, Vietnam, Princeton University, Cu Chi Health Department
- Responsible party
- Sponsor
- Investigators
- Stephen Baker, PhD, Principal investigator, Oxford University Clinical Research UnitNghia Ho Dang Trung, PhD, MD, Principal investigator, Pham Ngoc Thach University of MedicineAndrea Graham, PhD, Principal investigator, Princeton University, USAJacqueline Leung, MA, Study director, Princeton University, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02597556
- Sponsor's protocol ID
- 16EN
- Status last verified
- Dec 2016
- First submitted
- 3 Nov 2015
- Last updated
- 15 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Blackwell AD, Martin M, Kaplan H, Gurven M. Antagonism between two intestinal parasites in humans: the importance of co-infection for infection risk and recovery dynamics. Proc Biol Sci. 2013 Aug 28;280(1769):20131671. doi: 10.1098/rspb.2013.1671. Print 2013 Oct 22.
PubMed 23986108Ezenwa VO, Jolles AE. Epidemiology. Opposite effects of anthelmintic treatment on microbial infection at individual versus population scales. Science. 2015 Jan 9;347(6218):175-7. doi: 10.1126/science.1261714.
PubMed 25574023Ferrari N, Cattadori IM, Rizzoli A, Hudson PJ. Heligmosomoides polygyrus reduces infestation of Ixodes ricinus in free-living yellow-necked mice, Apodemus flavicollis. Parasitology. 2009 Mar;136(3):305-16. doi: 10.1017/S0031182008005404. Epub 2009 Jan 21.
PubMed 19154651Knowles SC, Fenton A, Petchey OL, Jones TR, Barber R, Pedersen AB. Stability of within-host-parasite communities in a wild mammal system. Proc Biol Sci. 2013 May 15;280(1762):20130598. doi: 10.1098/rspb.2013.0598. Print 2013 Jul 7.
PubMed 23677343Pedersen AB, Antonovics J. Anthelmintic treatment alters the parasite community in a wild mouse host. Biol Lett. 2013 May 8;9(4):20130205. doi: 10.1098/rsbl.2013.0205. Print 2013 Aug 23.
PubMed 23658004Nacher M. Worms and malaria: resisting the temptation to generalize. Trends Parasitol. 2006 Aug;22(8):350-1; author reply 351-2. doi: 10.1016/j.pt.2006.06.003. Epub 2006 Jun 23. No abstract available.
PubMed 16798090Rousham EK. An increase in Giardia duodenalis infection among children receiving periodic Anthelmintic treatment in Bangladesh. J Trop Pediatr. 1994 Dec;40(6):329-33. doi: 10.1093/tropej/40.6.329.
PubMed 7853436Taylor-Robinson DC, Maayan N, Soares-Weiser K, Donegan S, Garner P. Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance. Cochrane Database Syst Rev. 2015 Jul 23;2015(7):CD000371. doi: 10.1002/14651858.CD000371.pub6.
PubMed 26202783Leung JM, Hong CT, Trung NH, Thi HN, Minh CN, Thi TV, Hong DT, Man DN, Knowles SC, Wolbers M, Hoang Nle T, Thwaites G, Graham AL, Baker S. The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial. Trials. 2016 Jun 6;17(1):279. doi: 10.1186/s13063-016-1406-1.
PubMed 27266697
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Impact of Anthelmintic Treatment on the Incidence of Diarrheal Disease in School Children in Southern Vietnam
- ClinicalTrials.gov ID
- NCT02597556
- Acronym / sponsor ID
- 16EN
- Conditions
- Intestinal Helminthiasis, Diarrhea
- Keywords
- Albendazole, Ancylostoma duodenale, Ascariasis lumbricoides, Coinfection, Diarrhea, Helminths, Necator americanus, Microbiota
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The prevalence of worm infections in the site is significantly lower than expected
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Oxford University Clinical Research Unit, VietnamUniversity, hospital or other
- Collaborators
- Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Ho Chi Minh Preventive Medicine Centre, Vietnam, Princeton University, Cu Chi Health Department
- Study start
- Feb 2016
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 5 Nov 2015 (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.
Cheap and effective drugs called 'anthelmintics' are routinely administered to children in developing countries to eliminate infections by parasitic helminths. However, the effects of anthelmintic treatment on other pathogens (e.g., bacteria, viruses, protozoa) remain unknown. The aim of this study is to investigate the impact of anthelmintic treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam. Diarrheal disease remains a substantial cause of morbidity and mortality in children in Vietnam, and these children are typically co-infected with intestinal helminths. As helminths and diarrheal pathogens infect the same intestinal niche, anthelmintic treatments may alter host immune responses and the composition of the gut microbiota in ways that affect infection and disease risks caused by diarrheal pathogens.
This study will recruit 350 helminth-infected and 350 helminth-uninfected children aged 6-15 years. Recruited children will be randomized to receive either anthelmintic or placebo treatment once every three months and will be monitored for incidences of diarrheal disease for 12 months. At the 12-month time point, all children will receive anthelmintic treatment. Blood and stool samples will be collected throughout the study and used for evaluation of anemia and host immune responses, and for classification of gut microbes and parasite detection, respectively. The interventional study proposed here will provide an important first test of whether anthelmintic treatments have any indirect effects on infections caused by diarrheal pathogens.
Detailed description
This study is a randomized, double-blind, placebo-controlled trial to evaluate the effects of 400 mg albendazole treatment against placebo on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. Children will be enrolled from three primary schools in Cu Chi district in Ho Chi Minh City, Vietnam. Children will be screened for infections by the four most common soil-transmitted helminths, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, and Ancylostoma duodenale. Infected and uninfected individuals will be recruited into the study and randomized to either receive albendazole treatment once every three months for 12 months, or to placebo once every three months for 9 months, after which albendazole treatment will be given at month 12, in accordance with the current deworming schedule in Cu Chi district. A questionnaire regarding the participant's demographics, his/her daily habits, and potential sources of infection will be administered at baseline. Weekly active and passive surveillance of diarrheal cases will be conducted throughout the study, and a health questionnaire will be administered during all cases of diarrhea and at the end of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Albendazole | Active comparator | Drug: AlbendazoleAlbendazole will be administered as a single 400mg chewable tablet at 0, 3, 6, 9, and 12 months. |
| Placebo | Placebo comparator | Drug: PlaceboMatching Placebo will be administered as a single chewable tablet at 0, 3, 6, and 9 months. At month 12, all participants will receive a single 400mg Albendazole tablet. |
Who may qualify
- Ages
- 6 to 15 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Between 6-15 years of age
- Written informed consent from a parent or guardian
- Written assent from children >10 years of age
Key exclusion criteria (2 listed)
- Subjects who do not fulfill any component of the inclusion criteria
- Subjects that are both hookworm-positive and anemic, as defined by the WHO guidelines
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 |
|---|---|---|
| AlbendazoleA single 400mg dose of Albendazole administered at 0, 3, 6, 9, and 12 months. | Drug | Albendazole |
| PlaceboMatching placebo tablet administered at 0, 3, 6, and 9 months. At month 12, all participants will receive a single dose of 400mg Albendazole. | Drug | Placebo |
Primary outcome
Incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance
Time frame: 12 months
Incidence of diarrhea will be defined according to WHO guidelines as three or more loose stools in a 24-hour period or at least one bloody/mucoid stool. To be considered a new episode of diarrhea, at least three intervening days of normal stools without other gastrointestinal symptoms need to have passed between diarrhea occurrences.
6 secondary outcomes
Prevalence and intensity of soil-transmitted helminth infections by real-time PCR and microscopy
Time frame: Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases
Prevalence and intensity of enteric viruses and bacteria that cause diarrhea assessed by real-time PCR and the Luminex xTAG Gastrointestinal Pathogen Panel
Time frame: Time Frame: Baseline, 3, 6, 9, and 12 months, and during and two weeks after diarrhea cases
Changes in fecal microbiota composition by Illumina sequencing
Time frame: Baseline, 0.5, 3, 6, 6.5, 9, and 12 months, and during and two weeks after diarrhea cases
Changes in blood cytokine (Th1, Th2, TH17, and Treg) levels by bead-based immunoassays
Time frame: Baseline, 6, and 12 months of study
Antibody isotype response to helminth and diarrheal antigens by ELISA
Time frame: Baseline, 6, and 12 months
Mean z-scores (height-for-age, weight-for-age, weight-for-height)
Time frame: Baseline and 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2016.
- Background: PubMed 23986108Blackwell AD, Martin M, Kaplan H, Gurven M. Antagonism between two intestinal parasites in humans: the importance of co-infection for infection risk and recovery dynamics. Proc Biol Sci. 2013 Aug 28;280(1769):20131671. doi: 10.1098/rspb.2013.1671. Print 2013 Oct 22.
- Background: PubMed 25574023Ezenwa VO, Jolles AE. Epidemiology. Opposite effects of anthelmintic treatment on microbial infection at individual versus population scales. Science. 2015 Jan 9;347(6218):175-7. doi: 10.1126/science.1261714.
- Background: PubMed 19154651Ferrari N, Cattadori IM, Rizzoli A, Hudson PJ. Heligmosomoides polygyrus reduces infestation of Ixodes ricinus in free-living yellow-necked mice, Apodemus flavicollis. Parasitology. 2009 Mar;136(3):305-16. doi: 10.1017/S0031182008005404. Epub 2009 Jan 21.
- Background: PubMed 23677343Knowles SC, Fenton A, Petchey OL, Jones TR, Barber R, Pedersen AB. Stability of within-host-parasite communities in a wild mammal system. Proc Biol Sci. 2013 May 15;280(1762):20130598. doi: 10.1098/rspb.2013.0598. Print 2013 Jul 7.
- Background: PubMed 23658004Pedersen AB, Antonovics J. Anthelmintic treatment alters the parasite community in a wild mouse host. Biol Lett. 2013 May 8;9(4):20130205. doi: 10.1098/rsbl.2013.0205. Print 2013 Aug 23.
- Background: PubMed 16798090Nacher M. Worms and malaria: resisting the temptation to generalize. Trends Parasitol. 2006 Aug;22(8):350-1; author reply 351-2. doi: 10.1016/j.pt.2006.06.003. Epub 2006 Jun 23. No abstract available.
- Background: PubMed 7853436Rousham EK. An increase in Giardia duodenalis infection among children receiving periodic Anthelmintic treatment in Bangladesh. J Trop Pediatr. 1994 Dec;40(6):329-33. doi: 10.1093/tropej/40.6.329.
- Background: PubMed 26202783Taylor-Robinson DC, Maayan N, Soares-Weiser K, Donegan S, Garner P. Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance. Cochrane Database Syst Rev. 2015 Jul 23;2015(7):CD000371. doi: 10.1002/14651858.CD000371.pub6.
- Derived from this study: PubMed 27266697Leung JM, Hong CT, Trung NH, Thi HN, Minh CN, Thi TV, Hong DT, Man DN, Knowles SC, Wolbers M, Hoang Nle T, Thwaites G, Graham AL, Baker S. The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial. Trials. 2016 Jun 6;17(1):279. doi: 10.1186/s13063-016-1406-1.
- Oxford University Clinical research UnitLink provided by the sponsor.
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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.
Stephen Baker, PhD principal investigator
Oxford University Clinical Research Unit
Nghia Ho Dang Trung, PhD, MD principal investigator
Pham Ngoc Thach University of Medicine
Andrea Graham, PhD principal investigator
Princeton University, USA
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 Albendazole in people with Intestinal Helminthiasis and Diarrhea, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.
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 3 inclusion and 2 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: withdrawn, as of the sponsor's last update on 15 Dec 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 Vietnam. 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. Some participants in this study may receive a placebo. 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 was withdrawn before enrolling participants, so there are no results.
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?
Incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance (time frame: 12 months). 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 NCT02597556, which also lists 9 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 15 Dec 2016.