Lifestyle interventions to prevent diabetes in pregnant mothers
| ISRCTN | ISRCTN18467720 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18467720 |
| Secondary identifying numbers | MR/R020345/1 |
- Submission date
- 19/11/2018
- Registration date
- 21/12/2018
- Last edited
- 09/07/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
Diabetes during pregnancy or gestational diabetes mellitus (GDM) is associated with significant pregnancy-related complications, morbidity in newborns, and a long-term risk of developing type 2 diabetes, obesity and cardiovascular disease in both the mother and the offspring. In pregnant women with GDM, blood sugar usually returns to normal levels after delivery. However, about 50-70% of GDM mothers develop type 2 diabetes within 5-10 years after the birth of the child. Simple lifestyle interventions such as dietary modification and regular physical activity have shown to improve blood sugar levels and constitute potentially attractive options to reduce the risk of GDM. The current study aims to investigate if diet and/or physical activity intervention from earlier than 18 weeks of pregnancy helps reduce the risk of developing diabetes during pregnancy.
Who can participate?
Pregnant women aged 18 years or older and over and pregnancy for 16 weeks or less duration with at least one risk factor for developing diabetes during pregnancy.
What does the study involve?
Eligible women will be randomly allocated to one of the four treatment groups – diet, physical activity, diet and physical activity or standard care. In the dietary intervention, women will have to consume 200 g of fermented yoghurt daily. Women randomized to the physical activity (PA) group will have to undertake daily walking calculated as 40% more than their baseline activity monitored by device and the diet and PA group will have both interventions as above. All interventions will last for a minimum duration 14 weeks from randomization. Women allocated to standard care arm will serve as controls and will not be subjected to any active intervention, but will receive routine care by their treating physician. Participants will be studied for development of diabetes at 26 - 28 weeks and 32 weeks of pregnancy. Women who are diagnosed to have diabetes at 26-28 weeks could voluntarily withdraw from interventions or continue to 32 weeks on active interventions along with appropriate diabetes management as per local clinical practice. At 32 weeks of pregnancy final assessment of diabetes status will be done and all study procedures will be completed. Data of the mother and the newborn's health will be collected at delivery.
What are the possible benefits and risks of participating?
The possible benefit for participants is better pregnancy care and early screening for diabetes. The current study provides women with experience of specific healthy lifestyles during pregnancy. The opportunity to bring about behavioural changes during early pregnancy by changing mother’s nutrition and increasing physical activity to prevent GDM can have immediate and lifelong health impacts on the mother, as well as the newborn, with possible positive consequences into adulthood. There are no known risks to participants taking part in the study. Both yoghurt and physical activity are generally considered safe during pregnancy.
Where is the study run from?
The study is run from the Oxford Centre for Diabetes, Endocrinology and Metabolism (UK) and will take place in a centre in India and a centre in The Gambia
When is the study starting and how long is it expected to run for?
September 2018 to September 2022
Who is funding the study?
1. Medical Research Council (UK)
2. Director of Biotechnology (India)
3. Global Challenges Research Fund (UK)
Who is the main contact?
Dr Senthil Vasan
senthil.vasan@ocdem.ox.ac.uk
Contact information
Public
Oxford Centre for Diabetes, Endocrinology and Metabolism
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
 ORCID ID |
0000-0002-3630-6568 |
|---|---|
| Phone | +44 (0)7575323737 |
| senthil.vasan@ocdem.ox.ac.uk |
Scientific
Oxford Centre for Diabetes, Endocrinology and Metabolism
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
| Phone | +44 1865 857222 |
|---|---|
| fredrik.karpe@ocdem.ox.ac.uk |
Study information
| Study design | Interventional 2x2 factorial randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Pregnancy-Related Interventions in Mothers at Risk for gestational Diabetes in Asian India and Low and middle income countries (PRIMORDIAL Study) |
| Study acronym | PRIMORDIAL |
| Study hypothesis | Daily yoghurt and/or daily walking for at least 14 weeks will reduce the risk of developing gestational diabetes in ‘high-risk’ pregnant women |
| Ethics approval(s) | 1. Oxford Tropical Research Ethics Committee (OxTREC), 01/11/2018, 44-18 2. Christian Medical College, Vellore, 27/06/2018, IRB:11367 3. Scientific Co-ordinating Committee, MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, 13/11/2018, SCC 1645v1.1 |
| Condition | Gestational diabetes mellitus |
| Intervention | Current interventions as of 17/06/2020: Participants will be randomly allocated to either the intervention or the control group. Participants in the intervention group will be further randomised to receive either 200 g/day yoghurt, a physical activity intervention or both. This physical activity intervention will involve daily walking to a step count 40% higher than their baseline physical activity recorded during run-in-phase. Participants in the control group will receive standard care with no specific intervention Randomisation will be centre specific and stratified based on age and body mass index within each randomisation block. The total duration of the intervention is 14 weeks. Participants will be randomised within 2 weeks of screening and active intervention will continue till 32 weeks as per protocol. However, if any participant develops diabetes prior to 32 weeks, further continuation in the intervention will depend on safety, the effect of continuing interventions on pregnancy and subject to the investigator. GDM will be managed according to local guidelines in these participants. _____ Previous interventions from 07/05/2020 to 16/06/2020: Participants will be randomly allocated to either the intervention or the control group. Participants in the intervention group will be further randomised to receive either 200 g/day yoghurt, a physical activity intervention or both. This physical activity intervention will involve daily walking to a step count 40% higher than their baseline physical activity. Participants in the control group will receive standard care with no specific intervention. Randomisation will be centre specific and stratified based on age and body mass index within each randomisation block. The total duration of intervention is 14 weeks. Participants will be randomised at ≤ 18 weeks gestation and the intervention will continue till 32 weeks as per protocol. However, if any participant develops diabetes prior to 32 weeks, active trial interventions will be stopped. _____ Previous interventions: Participants will be randomly allocated to either the intervention or the control group. Participants in the intervention group will be further randomised to receive either 200 g/day yoghurt, a physical activity intervention or both. This physical activity intervention will involve daily walking to a step count 40% higher than their baseline physical activity, or walking daily to a step count of 11,000 steps (whichever is the greatest). Participants in the control group will receive standard care with no specific intervention. Randomisation will be centre specific and stratified based on age, body mass index and history of gestational diabetes during previous pregnancy within each randomisation block. The total duration of intervention is 14 weeks. Participants will be randomised at 18 weeks gestation and the intervention will continue till 32 weeks as per protocol. However, if any participant develops diabetes prior to 32 weeks, active trial interventions will be stopped. |
| Intervention type | Mixed |
| Primary outcome measure | Current primary outcome measure as of 07/05/2020: Incidence of gestational diabetes mellitus diagnosed based on IADPSG criteria at 26-28 weeks or fasting plasma glucose ≥5.1 mmol/l at week 32 (plasma glucose analysed using a Roche Cobas 800 Enzymic autoanalyser) _____ Previous primary outcome measure: Incidence of gestational diabetes mellitus according to IADPSG criteria, assessed by the following during weeks 26-28 of gestation and at 32 weeks of gestation: 1. Fasting plasma glucose, analysed using a Roche Cobas 800 Enzymic autoanalyser 2. Glucose at 1 and 2 hours post 75 g oral glucose tolerance test (OGTT), analysed using a Roche Cobas 800 Enzymic autoanalyser |
| Secondary outcome measures | Current secondary outcome measures as of 07/05/2020: 1. Absolute values of fasting blood glucose concentration at 32 weeks gestational age 2. Gestational weight gain using a Digital Tanita scale (in The Gambia) and a stadiometer (in India) from randomisation to week 32 3. Blood pressure from randomisation to week 32 4. Proportion of women undergoing instrumental/caesarean delivery, assessed using the study proforma 5. Post-partum haemorrhage,assessed using the amount of blood loss after child birth from the study proforma at delivery 6. Pre-eclampsia and eclampsia, assessed using clinical diagnosis of hypertension and proteinuria (with or without seizures) from the study proforma after 28 weeks of gestation 7. Blood loss at delivery, assessed using the amount of blood loss during the delivery from the study proforma at delivery 8. Pre-term births (less than 37 weeks of gestation), determined by calculating gestational age from dating the ultrasound scan at delivery 9. Foetal macrosomia (defined as birth weight >2 standard deviations above the population-specific mean in each setting), assessed from birth weight measured using an infantometer at delivery 10. Birth weight, assessed using an infantometer at delivery 11. Physical condition of newborn infant, assessed using the clinically recorded APGAR score at 1 and 5 minutes of birth 12. Length of newborn, assessed by measuring length from the head to the heel using a non-stretchable tape within 48 hours of birth. 13. Barriers to interventions in pregnancy, assessed using a questionnaire at screening and at 32 weeks of gestation _____ Previous secondary outcome measures: 1. Gestational weight gain, assessed using a Digital Tanita scale (in The Gambia) and a stadiometer (in India) at screening, the run-in phase, the point of randomisation, visits 1, 2 and 3, and at delivery (prior to birth) 2. Requirement of insulin/metformin post-OGTT, assessed through a review of patient notes from the diagnosis of GDM to delivery 3. Proportion of women undergoing instrumental/caesarean delivery, assessed using the study proforma after delivery 4. Gestational age at delivery, determined by dating the ultrasound scan at delivery 5. Post-partum haemorrhage, assessed using the amount of blood loss after child birth from the study proforma at delivery 6. Pre-eclampsia and eclampsia, assessed using clinical diagnosis of hypertension and proteinuria (with or without seizures) from the study proforma after 28 weeks of gestation 7. Blood less at delivery, assessed using the amount of blood loss during the delivery from the study proforma at delivery 8. Pre-term births (less than 37 weeks of gestation), determined by calculating gestational age from dating the ultrasound scan at delivery 9. Foetal macrosomia (defined as birth weight >2 standard deviations above the population-specific mean in each setting), assessed from birth weight measured using an infantometer at delivery 10. Low birth weight (defined as birth weight <2.5 kg), assessed using an infantometer at delivery 11. Physical condition of newborn infant, assessed using the clinically recorded APGAR score at 1 and 5 minutes of birth 12. Length of newborn, assessed by measuring length from the head to the heel using a non-stretchable tape within 48 hours of birth 13. Ponderal index, assessed using the formula (birth weight (kg)/birth length (m))³ within 48 hours of birth 14. Abdominal circumference of the newborn, assessed by measuring the circumference at the level of the xiphisternum and just above/below the level of the umbilicus using non-stretchable tape within 48 hours of birth 15. Barriers to interventions in pregnancy, assessed using a questionnaire at screening and at 32 weeks of gestation |
| Overall study start date | 01/09/2018 |
| Overall study end date | 16/09/2022 |
Eligibility
| Participant type(s) | Other |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 1,856 pregnant women (928 from each site) |
| Total final enrolment | 1870 |
| Participant inclusion criteria | Current inclusion criteria as of 07/05/2020: 1. Aged 18 years or older 2. Gestational age ≤ 16 weeks 3. Meeting at least one of the following criteria for high-risk gestational diabetes mellitus (GDM): 3.1. Booking BMI ≥ 25kg/m² 3.2. Age ≥ 25 years 3.3. First-degree relative with diabetes 3.4. Previous pregnancy with GDM 3.5. Previous pregnancy with large baby (≥ 3.5kg) 3.6. Previous pregnancy with pre-eclampsia/eclampsia 3.7. History of PCOD/impaired fasting glucose) 4. Not currently on any medications (except iron, calcium or folic acid supplements, thyroxine supplement for hypothyroidism, low dose aspirin for pre-eclampsia) _____ Previous inclusion criteria: 1. Aged 18 years or older 2. Pregnant females 3. Gestational age >16 weeks 4. Meeting at least one of the following criteria for high-risk gestational diabetes mellitus (GDM): 4.1. BMI ≥25 kg/m² (for Indian women, BMI ≥23 kg/m² 4.2. First-degree relative with diabetes 4.3. Previous pregnancy with GDM 4.4. Previous pregnancy with a large baby (≥3.5 kg) 4.5. Previous pregnancy with pre-eclampsia/eclampsia 4.6. History of polycystic ovary disease (PCOD) or impaired fasting glucose 5. Not currently on any medications (excluding iron or folic acid supplements) |
| Participant exclusion criteria | Current inclusion criteria as of 07/05/2020: 1. GDM diagnosed prior to screening visit based on IADPSG criteria or documented raised HbA1C, i.e., either fasting glucose ≥ 5.1 mmol/L or 1h glucose ≥ 10.0 mmol/L or 2h glucose ≥ 8.5 mmol/L, or a documented HbA1c of ≥ 6.5% at first booking 2. History of pre-gestational diabetes 3. Multiple gestations in the current pregnancy 4. History of severe hyperemesis in the first trimester 5. Uncontrolled pre-gestational or gestational hypertension (BP > 150/100 mmHg) on treatment 6. History of recurrent (≥ 2) first-trimester spontaneous abortions or stillbirths 7. Previous child born with congenital anomalies 8. History of significant ante- or post-partum haemorrhage in the previous pregnancy 9. Pregnancy following in-vitro fertilization or any assisted reproductive technology 10. Previous or current psychiatric illness on medication, epileptic seizures or on antiepileptic medication 11. Women meeting absolute contraindications for physical activity during pregnancy as recommended by the ACOG 11.1. Heart disease 11.2. Restrictive lung disease 11.3. incompetent cervix/cerclage 11.4. Pregnancies at risk for premature labour 11.5. gestational hypertension (BP > 150/100 mmHg) 11.6. Severe anaemia _____ Previous exclusion criteria: 1. Diagnosis of pre-gestational diabetes, previous GDM based on The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria, or raised blood glucose at blooding - any of the following at first booking: 1.1. Fasting glucose ≥5.1 mmol/L 1.2. 1 hour glucose ≥10.0 mmol/L 1.3. 2 hour glucose ≥8.5 mmol/L 1.4. Documented HbA1c of ≥6.5% 2. Multiple gestation 3. History of severe hyperemesis in first trimester 4. History of hypertension (pre-gestational or gestational) 5. History or recurrent (more than two) first trimester abortions 6. History of ante- or post-partum haemorrhage in the previous pregnancy 7. Previous child born with congenital anomalies 8. Previous stillbirth or miscarriage 9. Pregnancy following in-vitro fertilisation or any assisted reproductive technology 10. Unwilling to adhere to the study protocol 11. History of or current psychiatric illness 12. History of or current neurological condition (i.e. epilepsy) 13. Meeting absolute contraindications for physical activity during preganncy as recommend by the American College of Obstetricians and Gynecologists (ACOG), including: 13.1. Heart disease 13.2. Restrictive lung disease 13.3. Incompetent cervix/cerclage 13.4. At risk for premature labour 13.5. Gestational hypertension 13.6. Severe anaemia |
| Recruitment start date | 01/02/2019 |
| Recruitment end date | 16/06/2022 |
Locations
Countries of recruitment
- Gambia
- India
Study participating centres
Vellore
632001
India
Fajara
273
Gambia
Sponsor information
University/education
Research Services, University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
| Phone | +44 (0)1865 (2)82106 |
|---|---|
| oxtrec@admin.ox.ac.uk | |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Government organisation / National government
- Alternative name(s)
- Dept. of Biotechnology, Govt of India, बायोटेक्नोलॉजी विभाग विज्ञान और प्रौद्योगिकी मंत्रालय, भारत सरकार, Department of Biotechnology, Department of Biotechnology, Ministry of Science & Technology, India, Department of Biotechnology, GOI, Dept. of Biotechnology, Govt. of India, Department of Biotechnology, Ministry of Sc & Tech, Govt of India, DBT
- Location
- India
No information available
Results and Publications
| Intention to publish date | 15/10/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The research findings will be disseminated in national and international platforms and through our network and collaborations. We anticipate publications in high impact international journals and presentation in relevant scientific meetings to inform researchers, clinicians and policy makers. The findings of general linterest will be publicised with the help of the Public Relations Office at the University of Oxford, which is well recognised for being an active communicant of research findings to the public through media. This includes an extensive open website and a full range of events organized during the National Science Week. Furthermore, the School of Medicine runs a very successful engagement programme, in which are its Science in Health, Public Lecture series and Science in Health LIVE event. |
| IPD sharing plan | Fully anonymized data will be available on written request from Dr. Senthil Vasan (senthil.vasan@ocdem.ox.ac.uk) after the completion of the study and publication of the primary research findings. All data meant for sharing will be anonymised/de-identified by removing all individual-level participant data and will be archived on the servers of the Archives department of Medical Research Council (MRC) at The Gambia indefinitely. Personally identifiable data will not be shared outside the research team. Data sharing will be in agreement with the MRC, The Gambia as outlined and governed by the Data Sharing Policies and MRC Policy and Guidance on Sharing of Research Data from Population & Patient Studies. The regulations will also adhere to the University of Oxford data policy guidelines. Informed consent for sharing research data with interested collaborators will be obtained from all participants. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 17/02/2021 | 22/02/2021 | Yes | No |
Editorial Notes
09/07/2024: The intention to publish date was changed from 15/07/2024 to 15/10/2024.
16/01/2024: The following changes were made to the trial record:
1. The total final enrolment was changed from 1864 to 1870.
2. The intention to publish date was changed from 15/01/2024 to 15/07/2024.
06/10/2023: The contact confirmed the record is up to date.
11/09/2023: The intention to publish date was changed from 01/09/2023 to 15/01/2024.
07/03/2023: The intention to publish date was changed from 01/03/2023 to 01/09/2023.
21/09/2022: The overall end date was changed from 22/09/2022 to 16/09/2022.
11/07/2022: The following changes have been made:
1. Recruitment resumed in India in June 2021 and in the Gambia in September 2020.
2. The recruitment end date has been changed from 31/03/2021 to 16/06/2022.
3. The final enrolment number has been added.
09/04/2021: The following changes have been made:
1. The overall trial end date has been changed from 21/08/2021 to 22/09/2022 and the plain English summary has been updated accordingly.
2. The intention to publish date has been changed from 26/12/2021 to 01/03/2023.
22/02/2021: Publication reference added.
22/06/2020: The scientific title has been changed from "PRIMORDIAL: Pregnancy-Related Interventions in MOthers Relating to DIAbetes In Asian India and Low-income countries" to "Pregnancy-Related Interventions in Mothers at Risk for gestational Diabetes in Asian India and Low and middle income countries (PRIMORDIAL Study)".
18/06/2020: Internal review.
17/06/2020: ORCID ID added, interventions and plain English summary updated. The trial was temporarily suspended from 23/03/2020 to 30/05/2020 due to public health regulations. The study has restarted from 01/06/2020 in India. In The Gambia, the study still remains suspended.
16/06/2020: The target number of participants was changed from 1,875 pregnant women to 1,856 pregnant women (928 from each site).
07/05/2020: The following changes were made to the trial record:
1. Due to current public health guidance, recruitment for this study has been paused.
2. The study design was changed from "Interventional 2x2 multi-factorial randomised controlled trial" to "Interventional 2x2 factorial randomized controlled trial".
3. The interventions were changed.
4. The primary outcome measure was changed.
5. The secondary outcome measures were changed.
6. The inclusion criteria were changed.
7. The exclusion criteria were changed.
8. The plain English summary was changed.
11/01/2019: Internal review.
