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.: PACTR202003893276712 Date of Approval: 02/03/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title PRObiotics and SYNbiotics in infants in Kenya; the PROSYNK study
Official scientific title PRObiotics and SYNbiotics in infants in Kenya; the PROSYNK study
Brief summary describing the background and objectives of the trial People exposed to poor sanitation and hygiene develop “environmental enteric dysfunction” (EED) characterised by abnormal intestinal histopathology, mucosal permeability defects, and inflammation. In young children, EED contributes significantly to poor growth through reduced digestion and absorption of nutrients, increased susceptibility to infections and systemic inflammation that directly inhibits growth hormones. EED likely results from pathogenic microbes colonising the gut despite exclusive breastfeeding and improved hygiene. A healthy gut microbiome may provide colonisation resistance against enteropathogens. Prebiotics are non-digestible compounds that encourage the growth of healthy gut bacteria. Synbiotics are prebiotics combined with live beneficial bacteria such as bifidobacteria and lactobacilli (“probiotics”). In a 52-month pilot project, we plan to administer probiotics or synbiotics to infants in Western Kenya over the first 0-5 months of life. We will assess whether these dietary supplements improve biomarkers of systemic inflammation, gut health and growth. We will also their impact on growth and episodes of common illnesses such as diarrhoea.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PROSYNK
Disease(s) or condition(s) being studied Digestive System,Nutritional, Metabolic, Endocrine,Paediatrics
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention
Anticipated trial start date 11/05/2020
Actual trial start date 28/10/2020
Anticipated date of last follow up 31/01/2024
Actual Last follow-up date 18/01/2024
Anticipated target sample size (number of participants) 600
Actual target sample size (number of participants)
Recruitment status Completed
Publication URL https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06211-1
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 Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Labinic synbiotic 5 billion CFU daily for first 10 days and weekly to age 6 months 0-5 months Prebiotic (BENEO Orafti Synergy1; 50 oligofructose:50 FOS; 200mg) + 3 live bacteria: Lactobacillus acidophilus NCFM, Bifidobacterium infantis Bi-26 and Bifidobacterium bifidum Bb-06; total of 5 billion organisms/day 150
Experimental Group Lab4b synbiotic 10 billion CFU daily for first 10 days and weekly to age 6 months 0-5 months Lab4b synbiotic: prebiotic (long-chain fructo-oligosaccharide 150mg/day + 4 live bacteria: Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20; total of 10 billion organisms/day 150
Experimental Group Lab4b probiotic 10 billion CFU/day; daily for 10 days then weekly to age 6 months 0-5 months Lab4b probiotic: 4 live bacteria: Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20; total of 10 billion organisms/day 150
Control Group No dietary supplement Not applicable Not applicable No dietary supplement 150 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
singleton newborn birthweight (BW) or current weight (if BW not known) 2000g well infant who is breastfed and has taken at least one breast feed well lives within the catchment area of the research centre at Homa Bay Hospital informed consent secured from mother/carer multiple pregnancy (e.g. twin/triplets) infant aged 4 days or older suspicion or presence of any acute illness (e.g. fever, receiving treatment with antibiotics) congenital abnormality that might be life-threatening or impair growth infant with potential contraindication to pre/synbiotics (e.g. suspected immune suppression; cardiac abnormality) mother unlikely to stay in study area for the duration of the study any health staff or study staff concerns regarding safety to participate in the trial Infant: 0 Month-23 Month 1 Day(s) 3 Day(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 16/10/2019 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
PO Box 54840-00200 Nairobi 54840 Kenya
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 01/10/2019 LSTM Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Pembroke Place Liverpool 111111 United Kingdom
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 03/10/2022 Kenya Medical Research Institute Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P. O. BOX 54840-00200, Nairobi Nairobi 00200 Kenya
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 30/09/2022 LSTM Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Pembroke Place, Liverpool, L3 5QA, UK Liverpool 111111 United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Plasma alpha-1-acid glycoprotein concentration Age 6 months
Secondary Outcome Biomarkers at ages 6 weeks and 3, 6 and 12 months 1. Stool biomarker of intestinal inflammation: Myeloperoxidase 2. Stool biomarker of increased intestinal permeability: α1-antitrypsin (AAT) 3. Plasma marker of chronic inflammation: alpha 1-Acid Glycoprotein at 6 weeks and 3 and 12 months 4. Plasma marker of acute inflammation: C-reactive protein (CRP) 5. Plasma marker of gut mucosal integrity: intestinal fatty acid binding protein (IFABP) 6. Plasma growth hormones: insulin-like growth factor (IGF)-1 and its carrier protein IGF binding protein 3 7. Stool pH Clinical outcomes to age 2 years 1. Mortality 2. Episodes of hospital admission 3. Episodes of all-cause sick-child clinic visits 4. Episodes of disease-specific sick-child clinic visits (e.g. diarrhoea; respiratory and skin infections) 5. Anthropometric outcomes: weight, length, mid-upper arm circumference (MUAC), head circumference Other outcomes 1. Feeding and WASH practices and environmental factors that likely influence the development of the gut microbiome assessed by questionnaires 2. Cognitive development assessed at 24 months 6 weeks and 3, 6, 12 and 24 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Homa Bay District Hospital Homa Bay Central Homa Bay Town Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Childrens Investment Fund Foundation 7 Clifford Street London 111111 United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Liverpool School of Tropical Medicine Pembroke Place Liverpool 111111 United Kingdom Research Institution
COLLABORATORS
Name Street address City Postal code Country
Linsday Hall Quadram Institute Bioscience, Norwich Research Park Norwich 111111 United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Iwaret Otiti Iwaret.Otiti@lstmed.ac.uk +254724007076 P.O.Box 1578
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Study Manager
Role Name Email Phone Street address
Principal Investigator Simon Kariuki SKariuki@kemricdc.org 254722205901 PO Box 1578
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Head of Malaria Research
Role Name Email Phone Street address
Scientific Enquiries Stephen Allen stephen.allen@lstmed.ac.uk 441517053752 Pembroke Place
City Postal code Country Position/Affiliation
Liverpool 111111 United Kingdom Prof Paediatrics
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Requests to access the fully-anonymised, raw data would be reviewed by the investigators based at LSTM and Kenya (or their representatives if appropriate). Approval to access the data will be granted only if the request is approved by all of the investigators. The KEMRI SERU and LSTM Research Ethics Committees will be notified of any agreements to share data. Informed Consent Form,Study Protocol Following publication of main findings Approval by investigators in UK and Kenya
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information