Contact information
Type
Scientific
Primary contact
Prof David Dunger
ORCID ID
Contact details
Department of Paediatrics
Box 116
Level 8 Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
dbd25@cam.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
REC Ref. 06/Q0108/350
Study information
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)
Acronym
APCam (Artificial Pancreas project at Cambridge)
Study hypothesis
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
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.
Study design
Phase II randomised controlled interventional crossover group trial
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 below to request a patient information sheet
Condition
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
Phase
Phase II
Drug names
Primary outcome measures
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.
Secondary outcome measures
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.
Overall trial start date
12/04/2007
Overall trial end date
23/09/2008
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
17
Participant 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
Recruitment start date
12/04/2007
Recruitment end date
23/09/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Department of Paediatrics
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Organisation
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge (UK)
Sponsor details
Box 277
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 OQQ
United Kingdom
stephen.kelleher@addenbrookes.nhs.uk
Sponsor type
Government
Website
Funders
Funder type
Charity
Funder name
Juvenile Diabetes Research Foundation (UK) (ref: 22-2006-1113; 22-2007-1801)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
European Foundation for Study of Diabetes (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Medical Research Council (MRC) (UK) - Centre for Obesity and Related metabolic Diseases (CORD)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
National Institute for Health Research (NIHR) (UK) - Cambridge Biomedical Research Centre
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20138357
2. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21216859
Publication citations
-
Results
Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodale M, De Palma A, Wilinska ME, Acerini CL, Dunger DB, Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial., Lancet, 2010, 375, 9716, 743-751, doi: 10.1016/S0140-6736(09)61998-X.
-
Results
Murphy HR, Elleri D, Allen JM, Harris J, Simmons D, Rayman G, Temple R, Dunger DB, Haidar A, Nodale M, Wilinska ME, Hovorka R, Closed-loop insulin delivery during pregnancy complicated by type 1 diabetes., Diabetes Care, 2011, 34, 2, 406-411, doi: 10.2337/dc10-1796.