Continuous glucose monitoring amongst pregnant women with early-onset type 2 diabetes
| ISRCTN | ISRCTN12804317 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12804317 |
| IRAS number | 331906 |
| Secondary identifying numbers | CPMS 58352, NIHR150958, IRAS 331906 |
- Submission date
- 19/10/2023
- Registration date
- 23/10/2023
- Last edited
- 01/11/2023
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
Previous studies have shown that Continuous Glucose Monitoring (CGM) improves maternal glucose, reduces neonatal admissions and is clinically and cost-effective in type 1 diabetes (T1D) pregnancy, and as a result CGM is now standard care in T1D pregnancy. However, there are no well-designed adequately powered trials to compare CGM and standard care monitoring of blood glucose in type 2 diabetes (T2D) pregnancy.
The purpose of this study is to examine whether using CGM improves glucose levels in pregnant women with T2D and whether it leads to better outcomes for the baby. We will also look at its impact on maternal wellbeing, diabetes treatment satisfaction, and cost effectiveness.
Who can participate?
We are aiming to recruit 422 pregnant women aged 16 years and above with T2D.
What does the study involve?
Eligible participants will be approached early in pregnancy and if consent is given they will be enrolled. All participants will wear a masked sensor for 7-14 days to collect baseline CGM data. Participants will then be randomly allocated to receive either study CGM or the current standard of care (fingerprick blood glucose monitoring, or continuous glucose monitoring) for the rest of pregnancy.
Study visits are aligned with routine antenatal visits every 4 weeks. A blood sample for metabolic phenotyping will be obtained at the recruitment visit. The participant will be asked to complete questionnaires at the recruitment visit and then again at around 32 weeks' gestation. Blood samples for HbA1c will be taken at baseline, 28-week, 32-week, and 36-week visits. Participants in the control arm will wear a masked sensor for 14 days at 20, 28, 32 and 36 weeks' gestation. Following delivery we will collect information on birth and infant. 20-25 participants will also be interviewed at baseline and around 32-36 weeks' gestation to examine, among other things, barriers and facilitators for CGM use in this population.
What are the possible benefits and risks of participating?
None
Where is the study run from?
University of East Anglia (UK)
When is the study starting and how long is it expected to run for?
May 2023 to April 2027
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK).
Who is the main contact?
Corinne Collett, C.Collett@uea.ac.uk
protect.trial@uea.ac.uk
Contact information
Scientific, Principal Investigator
Norwich Medical School, Floor 2, Bob Champion Research and Education Building, University of East Anglia, Norwich Research Park
Norwich
NR4 7UQ
United Kingdom
 ORCID ID |
0000-0002-5489-0614 |
|---|---|
| Phone | +44 (0)1603 591657 |
| Helen.Murphy@uea.ac.uk |
Scientific, Principal Investigator
LICAMM, LIGHT Laboratories, Clarendon Way, University of Leeds
Leeds
LS2 9JT
United Kingdom
| ORCID ID |
0000-0001-5395-8261 |
|---|---|
| Phone | +44 (0)113 343 7762 |
| E.M.Scott@leeds.ac.uk |
Public
Norwich Clinical Trials Unit
Norwich Medical School
University of East Anglia
Norwich
NR4 7TJ
United Kingdom
| ORCID ID |
0000-0002-5510-1488 |
|---|---|
| C.Collett@uea.ac.uk |
Public
Norwich Clinical Trials Unit
Norwich Medical School
University of East Anglia
Norwich
NR4 7TJ
United Kingdom
| protect.trial@uea.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Home, Hospital |
| Study type | Other |
| Scientific title | PRegnancy Outcomes using continuous glucose monitoring TEChnology in pregnant women with early-onset Type 2 diabetes: A multicentre randomised controlled trial of the clinical and cost-effectiveness of using continuous glucose monitoring (CGM) in pregnant women with early-onset type 2 diabetes |
| Study acronym | PROTECT |
| Study hypothesis | In pregnant women with early-onset type 2 diabetes, the use of real-time CGM is more effective than standard clinical care (finger-prick self-monitoring blood glucose testing, continuous glucose monitoring) for improving the percentage of time spent in the pregnancy target glucose range of 3.5-7.8 mmol/L and reducing clinically relevant neonatal morbidity (neonatal care admission) or perinatal death. |
| Ethics approval(s) |
Approved 19/09/2023, South Central - Berkshire B Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 2071048276; berkshireb.rec@hra.nhs.uk), ref: 23/SC/0315 |
| Condition | Early-onset type 2 diabetes in pregnancy |
| Intervention | Recruitment visit: When women have expressed their wish to participate, they will be invited for the recruitment visit, when the following activities will be performed by the research team: • Checking inclusion and exclusion criteria • Written informed consent • Baseline socio-demographic data collection • Relevant medical / obstetric history and present medical (diabetes, comorbidity, medication, and obstetric) information • Body weight and height, calculation of BMI • Early pregnancy HbA1c recorded (or performed if not previously done in this pregnancy) • Blood sample taken for metabolic phenotyping (C-peptide, autoantibodies, genetic risk score) • Baseline questionnaire pack provided for participants to complete at home (either paper or electronically via link) • Masked Freestyle Libre 3 sensor insertion (ideally 2 weeks prior to randomisation) Women will have a small glucose sensor inserted under the skin by the clinical research team and will be instructed to wear it at home for up to 14 days. They will not be able to see the glucose information from this sensor. Randomisation visit: Ideally the sensor will be in place for 14 days, however if necessary to meet timelines, at least 3-4 days of CGM data should be available prior to randomisation (prior to 16 weeks' gestation). At the randomisation visit, the following will be performed: • Masked CGM sensor upload & review (to confirm adequate baseline data available). Those randomised to the intervention arm will have access to the data from the masked sensor period following randomisation. • Collection / confirmation of completed baseline questionnaires • Record average total daily dose (TDD) of insulin during the previous 3 days • Randomisation via study website • Participant training Participants in the CGM group will be shown how to apply the sensor, how to understand and use the CGM apps, how to interpret the data to guide decisions on eating and activity, recommended targets, and metformin / insulin dose adjustment. Participants in the control arm will receive fingerstick self-monitoring blood glucose or continuous glucose monitoring training per local standard of care, along with advice on recommended targets, managing their diabetes in pregnancy, and metformin/insulin dose adjustment if relevant. Participants will use their allocated glucose monitoring method throughout pregnancy, until after delivery. Subsequent Study Visits Follow up visits will be every 4 weeks at ~16/40, 20/40, 24/40, 28/40, 32/40, 36/40. It is expected that study visits will align with routine NHS antenatal clinic visits however virtual study visits will be offered if appropriate. At these visits the following data will be recorded on the study database: • Weight • Blood pressure • Glucose monitoring method(s), frequency of glucose testing • Insulin delivery method(s), dose and type • Adverse events of special interest In addition, the following will be performed at key visits: • Masked CGM for control group participants (14 days data collection) at 20, 28, 32, and 36 weeks’ gestation • Blood collection for HbA1c at 28, 32, and 36 weeks’ gestation • Follow-up questionnaires at 32 weeks’ gestation Delivery visit The following obstetric and neonatal outcomes will be collected: • Mode of delivery (vaginal, instrumental, elective/emergency caesarean section) • Gestational age at delivery and indication for any preterm delivery <37 weeks • Infant(s) birth weight • Adverse events (pregnancy loss <24 weeks, stillbirth, neonatal death) Neonatal follow up Neonatal assessment is at hospital discharge (or 28 days if admission prolonged). The following data will be collected: • Neonatal morbidity (treatment for neonatal hypoglycaemia, neonatal jaundice, respiratory distress) • Neonatal care admission (duration of stay at each level of care) • Infant feeding at hospital discharge • Neonatal readmission in first 7 days after birth Questionnaires Participants will be asked to complete questionnaires at home, electronically or on paper, at baseline and again at 32 weeks: • T2D Distress Scale (DDS) • Glucose Monitoring Satisfaction Survey (GMSS) • Patient Health Questionnaire 9-item depression scale (PHQ-9) • Generalized Anxiety Disorder 7-item scale (GAD-7) • EQ-5D Optional qualitative interviews 20-25 participants will be purposively selected by socio-demographic factors to take part in the semi-structured interviews, in early pregnancy (after randomisation) and again at around 32-36 weeks' gestation. Interviews will take place remotely or in person. |
| Intervention type | Device |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Continuous glucose monitoring |
| Primary outcome measure | 1. Percentage time spent with maternal glucose levels within target range as recorded by CGM Time-In-Range (TIR 3.5-7.8mmol/l) from 20 until 38 weeks’ gestation or until delivery, if delivery is earlier than 38 weeks’ gestation 2. Neonatal unit admission or death (stillbirth/neonatal death) From randomisation to discharge after delivery (or 28 days post delivery if admission prolonged) |
| Secondary outcome measures | 1. HbA1c & CGM mean glucose, GMI, frequency & duration of glycaemic excursions [%Time-Above-Range (≥6.7 & ≥7.8mmol/L), %Time-Below-Range (≤3.5 & ≤3.0mmol/l)], glycaemic variability (glucose SD, CV)] From 20 until 38 weeks’ gestation or until delivery, if delivery is earlier than 38 weeks’ gestation 2. Hypertensive disorders from randomisation to discharge after delivery (or 28 days post delivery if admission prolonged) 3. Gestational weight gain from baseline (early pregnancy) to last visit prior to delivery 4. Diabetes treatment (metformin & insulin use) From 20 until 38 weeks’ gestation or until delivery, if delivery is earlier than 38 weeks’ gestation 5. Hospital admissions & duration of stay from randomisation to discharge after delivery (or 28 days post delivery if admission prolonged) 6. Severe hypoglycaemia, hyperosmolar hyperglycaemic state, and diabetic ketoacidosis episodes from randomisation to discharge after delivery (or 28 days post delivery if admission prolonged) 7. Gestational age at birth 8. Birth weight for gestational age (SDS) (GROW customised birth weight, LGA birth weight >90th centile or SGA <10th centile) at Birth 9. Mode of delivery at delivery 10. Neonatal unit admission >24hrs (duration of stay, highest level care) at Discharge after delivery 11. Adverse events (pregnancy loss <24 weeks, congenital anomaly (any), stillbirth, neonatal death) at Delivery 12. Birth injury (spinal cord injury, clavicular, skull or bone fracture, shoulder dystocia, nerve palsy, subdural or intracerebral haemorrhage, hypoxic ischaemic encephalopathy) at Birth 13. Neonatal morbidity (treatment for neonatal hypoglycaemia, respiratory distress requiring treatment, neonatal jaundice requiring treatment) at Discharge after delivery 14. Feeding at hospital discharge (exclusive breast-feeding / partial breast-feeding / exclusive formula feeding) at Discharge after delivery 15. Diabetes distress, anxiety & depression and treatment satisfaction using short questionnaires at Baseline & 32 weeks’ gestation 16. Qualitative study to explore the acceptability, barriers, and facilitators for CGM use in T2D pregnancy at Baseline & 32-36 weeks’ gestation 17. Incremental cost per quality-adjusted life year (QALY) at Randomisation to discharge after delivery |
| Overall study start date | 01/05/2023 |
| Overall study end date | 30/04/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 422; UK Sample Size: 422 |
| Participant inclusion criteria | 1. Type 2 diabetes (T2D) 2. 16 years of age or over 3. Confirmed pregnancy < = 14 weeks’ gestation 4. HbA1c of > = 43 mmol/mol (6.1%) in pregnancy (< = 14 weeks’ gestation) 5. Willingness to use the study devices throughout the trial 6. Able to provide informed consent |
| Participant exclusion criteria | 1. Non-type 2 diabetes 2. Chronic kidney disease (CKD) grade 4 or 5 (GFR < 30ml/min) 3. Severe visual impairment |
| Recruitment start date | 01/01/2024 |
| Recruitment end date | 28/02/2026 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Colney
Norwich
NR4 7UY
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
London
NW1 2PG
United Kingdom
Acre Street
Lindley
Huddersfield
HD3 3EA
United Kingdom
Birmingham
B4 6NH
United Kingdom
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Watford General Hospital
Vicarage Road
Watford
WD18 0HB
United Kingdom
St Marys Hospital
South Wharf Road
London
W2 1BL
United Kingdom
Eaglestone
Milton Keynes
MK6 5LD
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Herries Road
Sheffield
S5 7AU
United Kingdom
80 Newark Street
London
E1 2ES
United Kingdom
Crown Street
Liverpool
L8 7SS
United Kingdom
369 Fulham Road
London
SW10 9NH
United Kingdom
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
530 London Road
Thornton Heath
CR7 7YE
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Glen Road
London
E13 8SL
United Kingdom
Isleworth
TW7 6AF
United Kingdom
Sponsor information
University/education
Norwich Research Park
Earlham Road
Norwich
NR4 7TJ
England
United Kingdom
| Phone | +44 1603 289863 |
|---|---|
| researchsponsor@uea.ac.uk | |
| Website | https://www.uea.ac.uk/ |
"ROR" |
https://ror.org/026k5mg93 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/01/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Editorial Notes
01/11/2023: 2 public contacts were added.
19/10/2023: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
