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.: PACTR202210764744357 Date of Approval: 17/10/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Virutubisho
Official scientific title Optimizing nutrient requirement for maternal supplementation among women of reproductive age in Kenya
Brief summary describing the background and objectives of the trial Supplementation with multiple micronutrients has been shown to reduce prevalence of low birth weight and small for gestation age babies when given to pregnant women in nutritionally deficient populations. There are few studies measuring markers of microntrient status in pregnant women in LMICs before and after supplementation but evidence from the JiVita trial in Bangladesh suggests that the current dose formulation (UNIMMAP) is insufficient to achieve repletion. Bangladesh is not a malaria endemic area and deficiencies may vary according to geographic location, hence the need for studies in Kenya. The proposed trial will be a dose-finding trial of multiple micronutrient supplements in the form of powder to be taken in water with 3 arms: current standard of care and 2 arms: test dose 1 with moderately increased doses and test dose 2 with higher doses but below the safe upper level. Pharmacokinetic analysis of micronutrient markers using both rich and sparse sampling timepoints will predict optimal doses. The trial will take place in women of reproductive age aged 18-35 years and consist of 2 cohorts of 108 women: non-pregnant and pregnant women living in 2 locations of Kilifi North subcounty. Tolerability and safety of the supplements will be monitored.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) NA
Disease(s) or condition(s) being studied Nutritional, Metabolic, Endocrine
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 15/08/2023
Actual trial start date 05/12/2024
Anticipated date of last follow up 16/06/2026
Actual Last follow-up date 30/11/2026
Anticipated target sample size (number of participants) 216
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
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 Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Control MMS Nutrient MMS, mg Vitamin A 0.8 Vitamin D 0.005 Vitamin E 10 Vitamin B1 (Thiamine) 1.4 Vitamin B2 (Riboflavin) 1.4 Vitamin B3 (Nicotinamide)18 Vitamin B12 0.0026 Vitamin B6 1.9 Folate 0.4 Vitamin C 70 Iron 60 Zinc 15 Iodine 0.15 Selenium 0.065 Copper 2 Given orally once daily In non-pregnant cohort - 3 months In pregnant cohort- from enrolment at 14-20 wks gestation until delivery Multiple micronutrient supplement presented as powder to be dissolved in water 72 Active-Treatment of Control Group
Experimental Group Multiple micronutrients test dose 1 Nutrient MMS, mg Vitamin A 1.6 Vitamin D 0.01 Vitamin E 100 Vitamin B1 (Thiamine) 2.8 Vitamin B2 (Riboflavin) 2.8 Vitamin B3 (Nicotinamide) 35 Vitamin B12 0.125 Vitamin B6 3.8 Folate 0.6 Vitamin C 140 Iron 60 Zinc 20 Iodine 0.22 Selenium 0.13 Copper 2 Calcium 500 Phosphorus 500 Vitamin K 0.09 Pantothenic acid 7 Biotin 0.035 Choline 550 Potassium 2,000 Manganese 2.6 Magnesium 350 Given orally once daily In non-pregnant cohort - 3 months In pregnant cohort- from enrolment to delivery Multiple micronutrients powder dissolved in water 72
Experimental Group Multiple micronutrients test dose 2 Nutrient MMS, mg Vitamin A 2 Vitamin D 0.02 Vitamin E 300 Vitamin B1 (Thiamine) 5.6 Vitamin B2 (Riboflavin) 5.6 Vitamin B3 (Nicotinamide)70 Vitamin B12 0.25 Vitamin B6 7.6 Folate 0.78 Vitamin C 280 Iron 60 Zinc 30 Iodine 0.26 Selenium 0.26 Copper 2 Calcium 500 Phosphorus 500 Vitamin K 0.09 Pantothenic acid 7 Biotin 0.035 Choline 900 Potassium 2,000 Manganese 2.6 Magnesium 350 Given orally once daily In non-pregnant cohort- 3 months In pregnant cohort- from enrolment to delivery Multiple micronutrients powder dissolved in water 72
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Non-pregnant cohort Women aged 18-35 years Not pregnant and not lactating Not intending to move away for 6 months Negative pregnancy test and not intending to get pregnant during study Able and willing (in the investigator’s opinion) to comply with all study requirements Pregnant women cohort Women aged 18-35 years Pregnant with singleton pregnancy from 14 to less than or equal to 20 weeks gestation Not intending to move away for 6 months Able and willing (in the investigator’s opinion) to comply with all study requirements Non-pregnant women Known intolerance or allergy to constituents of IP Moderate or severe anaemia (Hb<8g/dL) or other nutritional conditions requiring immediate treatment Unwilling to substitute regular micronutrient supplements for the study product Pregnant women Known intolerance or allergy to constituents of IP Multiple pregnancy Moderate or severe anaemia (Hb<7g/dL) or other nutritional conditions requiring immediate treatment Unwilling to substitute regular micronutrient supplements for the study product Adult: 19 Year-44 Year 18 Year(s) 35 Year(s) Female
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 23/01/2023 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
KEMRI HQ, Off Raila Odinga Way Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Determination of optimal dosing of multiple micronutrient supplements (MMS) to correct micronutrient deficiencies among pregnant and non-pregnant women of reproductive age in Kilifi County, Kenya Doses predicted from pharmacokinetic models from doses given and micronutrient levels measured at baseline, during and at end of supplementation
Secondary Outcome Tolerability and safety of micronutrients described at different doses, including birth outcomes Continuously during period of supplementation
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI Wellcome Trust Research Programme Kilifi County Hospital,, off Bofa Road Kilifi 80108 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 500 5th Ave N Seattle 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford University Offices, Wellington Square Oxford OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Prof Sophie Moore Kings College, Westminster Bridge Road London SE1 7EH United Kingdom
Prof Joseph Standing UCL, 30 Guilford Street London WC1N 1EH United Kingdom
Dr. Akosua Agyeman UCL, 30 Guilford Street London WC1N 1EH United Kingdom
Dr. Zipporah Bukania KEMRI- Centre for Public Health Research OffRaila Odinga Way Nairobi 00200 Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Martha Mwangome MMwangome@kemri-wellcome.org +254733289040 KEMRI-Wellcome Trust Research Programme, Off Bofa Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Principal Researcher
Role Name Email Phone Street address
Public Enquiries Cynthia Mauncho CMauncho@kemri-wellcome.org +254730162000 KWTRP Off Bofa Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Head of Communication
Role Name Email Phone Street address
Scientific Enquiries Alison Talbert ATalbert@kemri-wellcome.org +254729218993 Kilifi County Hospital off Bofa Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Site lead
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The anonymised individual participant data will be archived and available for long-term in the KEMRI Wellcome Trust Research Programme Data Repository (https://dataverse.harvard.edu/dataverse/kwtrp). Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol From closeout of trial for 10 years Controlled data analysis permitted. External requests considered of adequate quality will be handled by the Programme Data Governance Committee.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://dataverse.harvard.edu/dataverse/kwtrp 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
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 31/01/2023 Approval later than anticipated 16 Jan 2023 15 Aug 2023
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 06/12/2024 SIV in November 2024 05 Dec 2024
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 31/01/2023 Approval later than anticipated 15 Apr 2024 15 Nov 2024
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 06/12/2024 Recruiting from December 2024 15 Nov 2024 16 Jun 2026
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 21/01/2025 Delayed start 30 Nov 2025
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 21/01/2025 Delayed start 30 Nov 2025 30 Nov 2026
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 06/12/2024 SIV concluded in November 2024 Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 31/01/2023 Ethics approval received FALSE, KEMRI Scientific and Ethics Review Unit, KEMRI HQ, Off Raila Odinga Way, Nairobi, 00200, Kenya, 24 Oct 2022, , +254202722541, kemriseru18@gmail.com, TRUE, KEMRI Scientific and Ethics Review Unit, KEMRI HQ, Off Raila Odinga Way, Nairobi, 00200, Kenya, 24 Oct 2022, 23 Jan 2023, +254202722541, kemriseru18@gmail.com, 24073_18743_4737.pdf