Prevention of nocturnal hypoglycaemia with closed-loop insulin delivery in children and adolescents with type 1 diabetes (T1D)

ISRCTN	ISRCTN18155883
DOI	https://doi.org/10.1186/ISRCTN18155883
Protocol serial number	REC Ref. 06/Q0108/350
Sponsor	Cambridge University Hospitals NHS Foundation Trust and University of Cambridge (UK)
Funders	Juvenile Diabetes Research Foundation (UK) (ref: 22-2006-1113; 22-2007-1801), European Foundation for Study of Diabetes (Germany), Medical Research Council (MRC) (UK) - Centre for Obesity and Related metabolic Diseases (CORD), National Institute for Health Research (NIHR) (UK) - Cambridge Biomedical Research Centre

Submission date: 03/06/2009
Registration date: 02/07/2009
Last edited: 27/04/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof David Dunger
Scientific

Department of Paediatrics
Box 116, Level 8 Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Email	dbd25@cam.ac.uk

Study information

Primary study design	Interventional
Study design	Phase II randomised controlled interventional crossover group trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Three randomised studies to assess closed-loop overnight glucose control as compared to standard pump therapy, copying with variable evening intake and afternoon exercise in youngsters with type 1 diabetes (T1D)
Study acronym	APCam (Artificial Pancreas project at Cambridge)
Study objectives	Closed loop systems can reduce risk of nocturnal hypoglycaemia in children and adolescents with type 1 diabetes (T1D) even after variable evening meal intake and differing exercise patterns.
Ethics approval(s)	Cambridge Local Ethics Committee approved on the 8th December 2006 (ref: 06/Q0108/350). The last substantive approval was granted on the 20th December 2007.
Health condition(s) or problem(s) studied	Type 1 diabetes
Intervention	The three studies will take place as follows: 1. Comparison of closed loop system with standard CSII (APCam01): In random fashion, twelve subjects aged 5 to 18 years were treated by overnight closed-loop or CSII on two separate occasions at the Clinical Research Facility 1 to 3 weeks apart. On both study occasions, the subjects consumed a self-selected meal (87 +/- 23g carbohydrates) at 18:00 accompanied by prandial insulin (9 +/- 5U) calculated according to subject's insulin-to-carbohydrate ratio. The meals were identical on both study nights. Closed-loop control was applied between 20:00 and 08:00 the next day. On the CSII night, the subject's standard insulin pump settings were applied. 2. Evaluation of the effects of a variable-content large evening meal (APCam02): Six subjects participating in APCam01, aged 12 to 18 years, were recruited for APCam02. They were studied on two further occasions 1 to 4 weeks apart. On each occasion at 18:00, the subjects consumed either a rapidly or slowly absorbed large meal selected from a list of standardised meals differing in glycaemic load (113 +/- 29 versus 40 +/- 8; rapid versus slow, P = 0.001, paired t-test) but matched for carbohydrates (129 +/- 34 versus 129 +/- 34 g; P = NS). The carbohydrate amount corresponded to the largest meal eaten over the three preceding months. Prandial insulin doses were comparable (17 +/- 6 versus 17 +/- 7 U) and were calculated according to subject's insulin-to-carbohydrate ratio. Closed-loop was performed from 18:30 to 08:00 the next day. 3. Effects of moderate-intensity evening exercise (APCam03): Nine post-pubertal subjects aged 12 to 18 years were studied on two occasions 1 to 5 weeks apart; four subjects participated previously in APCam01. One week before the first study occasion, a ramped treadmill protocol was used to estimate the peak VO2 as an indicator of the maximum oxygen uptake 15. Subsequently, subjects were studied after identical exercise protocols using closed-loop or CSII. On each occasion at 16:00, subjects consumed a light meal chosen from a list of standardised snacks (45 +/- 13 g carbohydrates) accompanied by prandial bolus calculated from subject's insulin-to-carbohydrate ratio. The subjects exercised at 55% VO2max on treadmill from 18:00 until 18:45 with a 5-minute rest at 18:20. Closed-loop was then performed overnight between 20:00 and 08:00. On the CSII night, subject's standard insulin pump settings were applied.
Intervention type	Other
Primary outcome measure(s)	Overnight glucose control including the assessment of variability and frequency of hypoglycaemic events. Measured from the start of the closed-loop (20:00 or 18:30) until 08:00 the next day, and from 00:00 until 08:00 the day after.
Key secondary outcome measure(s)	1. The time spent in A+B and E+F Grades of the glycaemic control grading scheme 2. The total overnight insulin dose 3. Endocrine effects of exercise on growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 1 (IGFBP-1) and counter-regulatory hormones Measured from the start of the closed-loop (20:00 or 18:30) until 08:00 the next day, and from 00:00 until 08:00 the day after.
Completion date	23/09/2008

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	5 Years
Upper age limit	18 Years
Sex	All
Target sample size at registration	17
Key inclusion criteria	1. Young subjects stratified into age for each of the three trials: 1.1. Trial 1: Aged 5 to 18 years, either sex 1.2. Trial 2: Aged 12 to 18 years, either sex 1.3. Trial 3: Aged Post-pubertal to 18 years, either sex 2. Type 1 diabetes for at least 6 months or confirmed C-peptide negative
Key exclusion criteria	1. Any other physical or psychological disease or medication likely to interfere with the normal conduct of the study and interpretation of the study results 2. Experienced recurrent severe hypoglycaemic unawareness 3. Clinical significant nephropathy, neuropathy or proliferative retinopathy
Date of first enrolment	12/04/2007
Date of final enrolment	23/09/2008

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Department of Paediatrics

Cambridge
CB2 0QQ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	27/02/2010		Yes	No
Results article	results	01/02/2011		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes