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.: PACTR202201638897606 Date of Approval: 14/01/2022
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Ntshembo (Hope) Trial
Official scientific title Intervention to optimise change in BMI of adolescent pre-conception to address the double burden of malnutrition: An RCT in rural and urban South Africa
Brief summary describing the background and objectives of the trial In Agincourt and Soweto, formative studies confirm a significant burden of malnutrition (persisting underweight, a high percentage of overweight/obesity, anaemia) and household food insecurity. Evidence from dietary data suggests that underweight and obesity may have some common underlying causes. Both may be the result of poor quality diets, undernutrition being the outcome of energy inadequate diets, and obesity the result of consuming large amounts of inexpensive, calorie-dense but nutrient-poor food. Both are the result of poverty and of households having too little financial resources to afford a diverse and healthy life. The purpose of this research is to optimise adolescent BMI in underweight and overweight/obese girls in order to reduce future metabolic risk and pre-conception exposures that contribute to transgenerational risk for metabolic disease. This will be achieved by: 1. In high-risk nulliparous adolescent girls, can a community health worker delivered intervention over 18-24 months involving nutrition (multi-micronutrient supplementation with dietary support) and lifestyle behavioural change, together with a household conditional-cash transfer: a. Achieve directionally appropriate changes in BMI in underweight and overweight/obese adolescent girls? b. Improve micronutrient status in underweight and overweight/obese adolescent? c. Positively influence individual behaviours relating to diet, physical activity, sedentary behaviours/sleep patterns? 2. Will these changes be sufficient to impact individual adolescent metabolic disease risk? 3. In those adolescent girls who become pregnant will reductions in the variance of BMI consequent on improvements in BMI status impact maternal glucose during pregnancy and new-born birth weight and adiposity? 4. Is the intervention package cost-effective? 5. How can the trial contribute to a national and and international strategy to tackle the adolescent double burden of malnutrition
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Phase II
Disease(s) or condition(s) being studied Nutritional, Metabolic, Endocrine
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention
Anticipated trial start date 01/07/2021
Actual trial start date 01/07/2021
Anticipated date of last follow up 30/11/2025
Actual Last follow-up date 30/03/2026
Anticipated target sample size (number of participants) 1248
Actual target sample size (number of participants) 1248
Recruitment status Recruiting
Publication URL pending
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 Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Treatment arm World Health Organization recommended multi-micronutrient supplement in tablet form will be provided to all adolescents (dosage - daily vs. twice/week - based on an altitude-adjusted haemoglobin point-of-care screening protocol to optimise iron stores and combat anaemia). Multi-micronutrient supplement (MMN): Based on 6-monthly point-of-care haemoglobin concentration assessments, the CHW will dispense and monitor the MMN use. The MMN supplement is based on WHO recommendations to improve nutrition and address anaemia, based on haemoglobin concentrations. - Non-anaemic women (Hb ≥12 g/dL at enrolment): Provision of a micronutrient supplement containing approximately 27 mg iron twice (2x) per week. - Mildly anaemic women (Hb <12 g/dL and >7g/dL at enrolment): Provision of a micronutrient supplement daily for six months - Severely anaemic women (Hb <7g/dL at baseline): Receive treatment regime according to the current standard of care in South African. Adolescent-level (i) Individual counselling support using HCS to facilitate appropriate goal-directed behaviour change; (ii) Health literacy interactive materials, co-developed with adolescents, on nutrition and sleep (detail below), and additional physical activity and sedentary behaviour modules for obese participants; (iii) WHO-recommended multi-micronutrient supplement in tablet form provided to all adolescents (dosage - daily vs. twice/week - based on an altitude-adjusted haemoglobin point-of-care screening protocol to optimise iron stores and combat anaemia), and (iv) support for dietary diversity in food choice. Family-level (i) Health literacy enhancing resources around food choice for better nutrition (e.g. the ‘food basket’ model); (ii) Support to ensure household members have accessed all social grants that they are eligible to receive; and (iii) Cash transfer to a co-resident primary female caregiver conditional on the engagement of both the adolescent and caregiver with the CHW and intervention activities (R280/month; approx. £15). 624
Control Group Control arm Call centre personnel will deliver a monthly telephonic programme on Life skills 18-24 months depending on when baseline data collection is completed Call centre personnel will deliver a monthly telephonic programme on Life skills for your future that will cover: (i) Education for your future (importance of education; selecting school subjects) (ii) Civic rights and responsibilities (how to apply for an identity document; what does it mean to vote?), (iii) Financial education (savings & budgets; how to set up a bank account; applying for a bursary), and (iv) Navigating social media (internet; various social media; benefits and harms of social media). For young women who become pregnant during the course of the trial, call centre assistants will link them with usual-care antenatal services provided by local primary care clinics. 624 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
-Adolescent girls and young women who are underweight (defined as BMI < 9th percentile for age by the WHO 2007 international reference) (BMI > 91st percentile) -overweight/obese (defined as BMI > 91st percentile for age by the WHO 2007 international reference) -Adolescent girls and young women aged 14-19 years -HIV negative -in school grades 8-11 -Adolescent girls and young women who are nulliparous - Presence of a primary female caregiver of the index adolescent participant resident in the same household -Girls with Type-1 diabetes -Previously identified severe intellectual disability -Evidence of severe depression based on a PHQ9 score of 20 and above (PHQ9 is used extensively in South Africa to monitor the severity of depression) -Adolescents screened HIV positive (However, they will be invited to participate in a sub-study and receive the intervention arm components, to provide important formative insights on a special population). Adolescent: 13 Year-18 Year 14 Year(s) 19 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 06/01/2022 Human Research Ethics Committee Medical University of the Witwatersrand
Ethics Committee Address
Street address City Postal code Country
Cnr York Road and 29 Princess of Wales Terrace Johannesburg, Parktown 2193 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Change in BMI standard deviation score (SDS) aligned to the target direction – i.e. increase in BMI for underweight, decrease in BMI for overweight/obese From baseline to follow-up at 18-24 months, or to early pregnancy if the participant becomes pregnant within the follow up period, compared to the controls
Secondary Outcome In the non-pregnant intervention group, blood pressure will be a key secondary outcome and together with other metabolic outcomes will be compared with measurements in non-pregnant controls. For those in the intervention group who become pregnant, maternal glucose concentrations around 28 weeks and neonatal adiposity data at delivery (sum of skin folds and ponderal index) will be compared with control pregnant participants and their offspring. 28 weeks and neonatal adiposity data at delivery
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
MRCWits Developmental Pathways for Health Research Unit College and Clinic Road Johannesburg 1864 South Africa
SAMRC Agincourt Unit Stand 1176, Bushbuckridge Local Municipality, Under headman Khosa, Under Amashangana Tribal Authority Bushbuckridge 1368 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Joint Global Health Trials UK MRC Wellcome Trust NIHR FCDO MRC London Institute of Medical Sciences, United Kingdom Parktown 2193 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Wits Health Consortium University of the Witwatersrand 31 Princess of Wales Terrace, Parktown Johannesburg 2193 South Africa University
COLLABORATORS
Name Street address City Postal code Country
Professor Alan Stein Oxford University, England Oxfordshire OX1 2JD United Kingdom
Professor Kathleen Kahn 27 St. Andrews Road Johannesburg 2193 South Africa
Professor Stephen Tollman 27 St. Andrews Road Johannesburg 2193 South Africa
Professor Nicola Christofides 60 York Road Johannesburg 2193 South Africa
Professor Lisa Micklesfield Corner College and Clinic Roads, Chris Hani Baragwanath Academic Hospital Johannesburg 1864 South Africa
Professor Shane Norris Corner College and Clinic Roads, Chris Hani Baragwanath Academic Hospital Johannesburg 1864 South Africa
Professor Ken Ong The Old Schools, Trinity Ln, Cambridge Cambridge CB2 1TN United Kingdom
Professor Chris Desmond 60 York Road Johannesburg 2193 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Shane Norris Shane.Norris@wits.ac.za +27829282381 Wits School of Public Health, University of the Witwatersrand
City Postal code Country Position/Affiliation
Parktown 2193 South Africa Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Kathleen Kahn Kathleen.Kahn@wits.ac.za +27117172617 Wits School of Public Health, University of the Witwatersrand
City Postal code Country Position/Affiliation
Parktown 2193 South Africa Principle Investigator
Role Name Email Phone Street address
Public Enquiries Shane Norris Shane.Norris@wits.ac.za +27829282381 University of the Witwatersrand, Wits School of Public Health
City Postal code Country Position/Affiliation
Johannesburg 2193 South Africa Principle Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We will comply and both summary results and link to these results and request to access data will be provided within 12 months of trial completion Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol The protocol and informed consent will be available for the period of the trial and once trial completed (5 years) Once the trial is completed there will be an embargo on the data for 12 months for the team to finalise the main trial publications, thereafter, scientists are welcome to submit requests to access data and/or samples to the PI (Norris) and via the Investigator Committee these requests will be evaluated. A comprehensive process will be detailed in the protocol paper that is currently being prepared for consideration for publication
URL Results Available Results Summary Result Posting Date First Journal Publication Date
pending 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