Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201707002361207 Date of Approval: 16/06/2017
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Study of interactions between intestinal microflora, intestinal macrofauna and antibiotic use in adults living in Lambaréné, Gabon
Official scientific title Study of interactions between intestinal microflora, intestinal macrofauna and antibiotic use in adults living in Lambaréné, Gabon: a phase I randomised participant blinded placebo controlled trial
Brief summary describing the background and objectives of the trial This study aims to assess the nature and extend of interactions between microflora, macrofauna and antibiotic administration in the gut of individuals living in sub-Saharan Africa. We intend to measure the variations of faecal helminth egg counts over time as the clinical indicator of the interactions and potential modification occurring when the microflora is depleted in individuals infected with helminths. Immune and molecular mechanisms associated with these changes of interactions will be addressed as well. The proposed study aims are: (1) To assess the association between the depletion of intestinal microbiota and the development of intestinal helminths in adults living in sub-Saharan Africa (2) To assess the safety profile and dynamics of gut microflora depletion following antibiotic administration (3) To describe the metabolomic changes in participants before and after microflora depletion and before and after receiving anti-helminthic treatment (4) To describe the patterns of peripheral innate immune responses after decontamination of the intestinal microbiota with specific reference to Th17-cells, B-cells, and ILC3s characterisation and levels of IL-17 and IL-22 changes. (5) To describe the intestinal microflora composition in the context of co-infection with helminthes (6) To characterize the phylogenetic and functional changes in the intestinal metagenome (bacterial, viral, fungal and parasitic) before, during and after intervention (7) To compare the microscopy, helminth PCR results with the metagenome sequencing in terms of the capability of parasite detection
Type of trial RCT
Acronym (If the trial has an acronym then please provide) FLORA 1
Disease(s) or condition(s) being studied Digestive System,Gut Flora and fauna
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 05/10/2015
Actual trial start date 05/11/2015
Anticipated date of last follow up 18/11/2017
Actual Last follow-up date 28/11/2017
Anticipated target sample size (number of participants) 40
Actual target sample size (number of participants) 38
Recruitment status Closed to recruitment,follow-up continuing
Publication URL NA
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised 1:1 study coordinator performing the randomization was indepedent from the recruitment team. Only one person was allow to allocate partiicpants to their repective treatments Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Neomycin 2g of Neomycin 3 times/day 10 days Neomycin antibiotics 20
Control Group Sucredulcor (Saccharine) 80 mg (4 tablets), 3 times a day 10 days Placebo 20 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
¿ Healthy males or females between the ages of 21 and 40 years ¿ Participants colonized with either Trichuris trichura or Ascaris lumbricoides; or co-infection both within a +/- 25% interval parasite load ¿ Negative for HIV, HBV and HCV serology. ¿ Body mass index between 18 and 30 ¿ Ability to understand and provide written informed consent ¿ Willingness to reside within the study area for the entire study duration (6 months) ¿ Pregnancy as determined by a positive urine hCG (if female). ¿ Currently lactating and breast-feeding (if female). ¿ Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies ¿ Serologic positivity for HIV, Hepatitis B or Hepatitis C ¿ History of vertigo, tinnitus or hearing loss ¿ Laboratory evidence of renal disease (serum creatinin greater than 1.25-times the upper reference limit, or more than trace protein or blood on urine dipstick testing). ¿ Body Mass Index greater than or equal to 30 or less than or equal to 18 ¿ Vital signs outside of acceptable range at Screening Visit (i.e., blood pressure >160/100, axillary temperature >38°C) ¿ History of active uncontrolled gastrointestinal disorders or diseases ¿ Chronic and or recurrent diarrhoea (diarrhoea defined as ¿ 3 loose stools per day) ¿ Chronic and or recurrent constipation ¿ Use of any of the following drugs within the last 1 months: antibiotics, antifungals, antivirals or antihelminthics (intravenous, intramuscular, or oral) ¿ Any on-going bacteraemia or pathogenic bacteria identified in stool culture ¿ Positive for Schistosoma spp,and S. Stercoralis ¿ Positive for filariasis 20 Year(s) 40 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/02/2014 National Ethics Committee Gabon
Ethics Committee Address
Street address City Postal code Country
BP 2217 Libreville Libreville BP 2217 Libreville Gabon
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Microscopic faecal parasite eggs counts of intestinal helminths will be determined at day 0 and day 30 using Kato-Katz faecal thick smear exams (eggs per gram of faeces). day 30
Secondary Outcome - Microscopic faecal parasite eggs count of intestinal helminths will be determined at the following time points: day 7, day 14,90, 120 and 180 day 7, day 14,90, 120 and 180
Secondary Outcome - Safety profile of gut flora depletion based on adverse events collection through the study period-frequency and severity of adverse events (AEs) and serious AEs. Day 0-day 180
Secondary Outcome - Sub-microscopic RT-PCR-based parasite eggs count of intestinal helminths will be determined at the following time points: days 0, 7, 14 30 and 90, 120 (table 1) - Metabolomics changes at day 30, 90, 120, 180. day 30, 90, 120, 180.
Secondary Outcome - Metabolomics changes at day 30, 90, 120, 180 day 30, 90, 120, 180
Secondary Outcome - Identification and quantification of gut flora colonies based on quantification of the 16S rRNA gene prior antibiotic administration and at days 7, 14, 30, and 90, 120 and 180 days 7, 14, 30, and 90, 120 and 180
Secondary Outcome Assessing peripheral circulating cytokine levels regardless the source: IL-17A, IL-17F, IL-22 days 1, 2, 7, 14, 30, 90, 120, 180
Secondary Outcome - Pattern of peripheral lymphocytes producing cytokines including (a) T-lymphocytes: Th1 (INF¿, TNF¿), Th2 ( IL-4, IL-13), Th17 (IL-17A, IL-6, IL-21), Treg (Foxp3, IL-10, TGFß) (b) B-lymphocytes (IL-6, IL-8, IL-17A, IL-17F, IL-10) and (c) ILCs: ILC3 (IL-17, IL-22, GM-CSF) days 1, 2, 7, 14, 30, 90, 120, 180
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre de recherches medical de Lambarene Lamabrene-Gabon Moyen Ogooue 242 Gabon
FUNDING SOURCES
Name of source Street address City Postal code Country
Centre de Recherches Medicales de Lambarene Lamabrene-Gabon Moyen Ogooue PO Box 242 Gabon
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital Lambaréné, Gabon Lamabrene-Gabon Moyen Ogooue PO Box 242 Gabon Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Institut für medizinische Mikrobiologie und Hygiene, Elfriede-Aulhorn Str. 6, 72076 Tübingen, Germany Aulhorn Str. 6, 72076 Tübingen, Germany Tübingen 6, 72076 Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Selidji Agnandji Todagbe agnandjis@cermel.org +24107353114 Lambarene
City Postal code Country Position/Affiliation
Moyen Ogooue PO Box 242 Gabon Centre de Rcherches Medicales de Lambarene-Gabon
Role Name Email Phone Street address
Public Enquiries Selidji Agnandji Todagbe agnandjis@cermel.org +24107353114 Lambarene
City Postal code Country Position/Affiliation
Moyen Ogooue PO Box 242 Gabon Centre de Rcherches Medicales de Lambarene-Gabon
Role Name Email Phone Street address
Scientific Enquiries Selidji Agnandji Todagbe agnandjis@cermel.org +24107353114 Lambarene
City Postal code Country Position/Affiliation
Moyen Ogooue PO Box 242 Gabon Centre de Rcherches Medicales de Lambarene-Gabon
REPORTING
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