Condition category
Nutritional, Metabolic, Endocrine
Date applied
09/04/2018
Date assigned
10/04/2018
Last edited
10/04/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Type 1 diabetes occurs when the body is unable to produce insulin, a hormone that controls the amount of sugar (glucose) in the blood. Closed-loop insulin delivery is a treatment approach for people with type 1 diabetes. It is a medical device consisting of a linked continuous glucose monitor (CGM) and an insulin pump. Previous studies have shown that closed loop insulin delivery may improve glucose control in pregnancy compared to treatment with a standard insulin pump and CGM. These results are important because improving glucose control improves pregnancy outcomes for both mother and baby. However, in the previous studies closed loop insulin delivery was only studied for a short duration in a small number of participants. As a result the aim of this study is to find definitive proof of a benefit to women by using automated closed-loop for about 24 weeks throughout pregnancy in a real-life NHS antenatal care setting.

Who can participate?
Pregnant women between 18 and 45 years of age with type 1 diabetes, between the 8th and 13th week of their pregnancy

What does the study involve?
Participants are randomly allocated to receive either the closed loop insulin delivery system or the current standard of care. All participants are asked to wear a continuous glucose monitor which records their glucose levels throughout their pregnancy. Participants attend their routine antenatal visits as usual. Additional blood samples are taken at the 24th and 34th week of pregnancy and questionnaires are also completed by the participant at the 34th week of pregnancy. Following this information on the birth is collected. 25 of the woman allocated to the closed loop insulin delivery system are also interviewed to collect more information on, among other things, their existing diabetes management practices, everyday work and family lives and their experience with the device.

What are the possible benefits and risks of participating?
Participating in this study may help participants to better understand what happens to their glucose levels during pregnancy. It will also help research into the development of closed-loop systems. Participants may also benefit from wearing a CGM and insulin pump. Recent studies suggest that using CGM helps to improve glucose control during pregnancy and reduces newborn complications related to higher glucose levels. Insulin pump use is usually associated with a reduced risk of low blood sugar and improved quality of life. The insulin pump and CGM sensor may produce mild pain when inserted under the skin. There is a low risk for developing a skin infection at the site of the insulin pump or CGM insertion. Itchiness, redness, bleeding, and bruising at the pump and CGM insertion sites may occur as well as tape allergies. Participants are asked to contact the study team if they have any skin problems. Participants are alerted by an alarm if the closed loop stops working or malfunctions in any way, for example loss of connection between the smartphone and insulin pump. If they do not respond to the alarm their usual insulin delivery will be automatically started. During the study participants may experience a ‘hypo’ as may happen in everyday life. This will be treated according to usual practice. It is possible that there will be a small amount of discomfort or bruising when the blood samples are taken.

Where is the study run from?
1. Norfolk and Norwich University Hospital (UK)
2. Cambridge University Hospitals NHS Foundation Trust (UK)
3. Royal Victoria Hospital, Belfast (UK)
4. The Ipswich Hospital NHS Trust (UK)
5. Manchester University Hospitals NHS Foundation Trust (UK)
6. King's College Hospital NHS Foundation Trust (UK)
7. Aberdeen Royal Infirmary (UK)
8. NHS Lothian (UK)
9. Leeds Teaching Hospitals NHS Trust (UK)
10. Harrogate and District NHS Foundation Trust (UK)
11. Derby Teaching Hospitals NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
January 2018 to January 2018

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Mr Matt Hammond

Trial website

Contact information

Type

Public

Primary contact

Mr Matt Hammond

ORCID ID

http://orcid.org/0000-0002-0739-3412

Contact details

NCTU
Norwich Medical School
UEA
Norwich
NR4 7TJ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

37660; IRAS Project ID: 240380

Study information

Scientific title

Evaluation of the biomedical and psychosocial impact of closed-loop (artificial pancreas) insulin delivery in women with type 1 diabetes during pregnancy

Acronym

ADAPT

Study hypothesis

Previous studies have shown that closed loop insulin delivery may improve glucose control in pregnancy compared to treatment with a standard insulin pump and continuous glucose monitor. These results are important because improving glucose control improves the pregnancy outcomes for both mother and baby. However, in the previous studies closed loop insulin delivery was only studied for a short duration in a small number of participants. As a result this trial focuses on determining the definitive proof of a benefit to women by using automated closed-loop for approximately 24 weeks duration throughout pregnancy in a real-life NHS antenatal care setting.

Ethics approval

NRES Committee East of England - Cambridge Central - approval pending

Study design

Randomised; Interventional; Design type: Treatment, Device

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Specialty: Diabetes, Primary sub-specialty: Type 1; UKCRC code/ Disease: Metabolic and Endocrine/ Diabetes mellitus, Reproductive Health and Childbirth/ Fetus and newborn affected by maternal factors and by complications of pregnancy, labour and deliver

Intervention

The trialists are aiming to recruit 124 pregnant women between 18 and 45 years of age with Type 1 Diabetes of at least 12 months’ duration. Participants will be approached between the 8th and 13th week of their pregnancy and if consent is given they will complete initial assessments and safety tests to confirm they are eligible to take part in the study. Following this eligible participants will be randomly allocated to receive either the closed loop insulin delivery system or the current standard of care. Randomisation will be performed by a computer based IWRS system on a 1:1 ratio.

The intervention being evaluated in this trial is automated closed-loop insulin delivery. The closed-loop system comprises of three components: an insulin pump, a continuous glucose monitor (CGM) and a computer-based model predictive control (MPC) algorithm to compute information from the CGM into a recommended insulin dose. Closed-loop systems are designed to deliver insulin in response to CGM glucose levels and may help to improve glucose control above and beyond what is currently achievable using standard insulin pumps and injections

All participants will be asked to wear a continuous glucose monitor which will record their glucose levels throughout their pregnancy. Participants will attend their routine antenatal visits as usual. Additional blood samples for the research will be obtained at the 24th and 34th week of pregnancy and questionnaires will also be completed by the participant at the 34th week of pregnancy. Following this we will collect information on the birth. 25 of the woman randomised to the closed loop insulin delivery system will also be interviewed to gain more information on, among other things, their existing diabetes management practices, everyday work and family lives and their experience with the device.

Intervention type

Device

Phase

Drug names

Primary outcome measures

The percentage of time spent with glucose levels between 3.9-7.8 mmol/L based on CGM levels at 24 and 34 weeks gestation. Data for the intervention group will be collected as part of the data collection from the AiD closed-loop system. The control group and those who have withdrawn from the intervention group will have a subcutaneous glucose sensor inserted by the clinical research team and will be instructed to wear it at home for 7-10 days. They will be asked to calibrate the CGM according to manufacturer instructions and to return for CGM sensor downloading within 14 days; Timepoint(s): End of the study

Secondary outcome measures

The following will be measured at 24 weeks and 34 weeks gestation:
1. Time spent with glucose levels between 3.9-7.8 mmol/L
2. Time spent with glucose levels above and below target range
3. Frequency and severity of hypoglycaemia episodes
4. Low and High Blood Glucose Index
5. Change in HbA1c level

The following will be measured following delivery;
1. Gestational weight gain
2. Gestational hypertension or preeclampsia
3. Mode of delivery
4. Gestational age at delivery and indication for any preterm delivery
5. Adverse events
6. Maternal hospital admissions
7. Hospital length of stay (both maternal and neonatal)
8. Neonatal morbidity
9. Infant birth weight
10. Neonatal intensive care unit (NICU) admission >24 hours
11. Infant feeding at hospital discharge (breast, bottle, both)

The following safety measures will be recorded on occurrence during the trial:
1. Frequency and severity of diabetic ketoacidosis
2. Number and severity of episodes of severe hypoglycaemia
3. Number and severity of episodes of adverse device effect

Overall trial start date

01/01/2018

Overall trial end date

01/01/2022

Reason abandoned

Eligibility

Participant inclusion criteria

1. Between 18 and 45 years of age (inclusive)
2. A diagnosis of type 1 diabetes (T1D), as defined by WHO for at least 12 months
3. A viable pregnancy confirmed by ultrasound, at gestational age ≥ 8 and up to 13 weeks and 6 days
4. Currently on intensive insulin therapy (≥3 injections or CSII)
5. Willingness to use the study devices and complete the CGM assessments
6. HbA1c level ≥48mmol/mol (≥ 6.5%) at booking (first antenatal contact) and <86 mmol/mol (<10%) at point of randomisation
7. Able to provide informed consent
8. Have access to email

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 124; UK Sample Size: 124

Participant exclusion criteria

1. Non-type 1 diabetes
2. Any other physical or psychological disease which, in the opinion of the investigator, is likely to interfere with the normal conduct and interpretation of the study results e.g. untreated coeliac disease or untreated hypothyroidism
3. Current treatment with drugs known to interfere with glucose metabolism as judged by the investigator such as high dose systemic corticosteroids, non-elective beta-blockers and MAO inhibitors
4. Known or suspected allergy against insulin
5. Women with advanced nephropathy (eGFR< 45), severe autonomic neuropathy, uncontrolled gastroparesis or severe proliferative retinopathy, as judged by the investigator, that is likely to interfere with the normal conduct of the study and interpretation of study results
6. Very good or very poor glycaemic control i.e. first antenatal HbA1c < = 48mmol/mol (< = 6.5%) and current HbA1c > 86mmol/mol (10%) . Women who enter pregnancy with HbA1c > 86mmol/mol (10%) may participate if they achieve HbA1c < 86mmol/mol (10%) before randomisation
7. Total daily insulin dose more than or equal to 1.5 IU/kg at booking
8. Severe visual or hearing impairment
9. Unable to speak and understand English

Recruitment start date

01/08/2018

Recruitment end date

31/12/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Norfolk and Norwich University Hospital
Colney Lane
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Royal Victoria Hospital, Belfast
Belfast
BT12 6BA
United Kingdom

Trial participating centre

The Ipswich Hospital NHS Trust
Ipswich
IP4 5PD
United Kingdom

Trial participating centre

Manchester University Hospitals NHS Foundation Trust
Manchester
M13 9WL
United Kingdom

Trial participating centre

King's College Hospital NHS Foundation Trust
London
SE5 9RJ
United Kingdom

Trial participating centre

Aberdeen Royal Infirmary
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

NHS Lothian
Edinburgh
EH10 5HF
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
LS1 3EX
United Kingdom

Trial participating centre

Harrogate and District NHS Foundation Trust
HG2 7SX
United Kingdom

Trial participating centre

Derby Teaching Hospitals NHS Foundation Trust
DE22 3NE
United Kingdom

Sponsor information

Organisation

Norfolk and Norwich University Hospitals NHS Foundation Trust

Sponsor details

Colney Lane
Norwich
NR4 7UY
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 16/35/01

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

A protocol paper will be submitted for publication during the trial and prior to the end of recruitment. The trialists plan to publish the results of the trial in a high-impact peer reviewed journal in early 2022 following analysis of the trial dataset.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/02/2022

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes