Condition category
Nutritional, Metabolic, Endocrine
Date applied
03/06/2009
Date assigned
02/07/2009
Last edited
27/04/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.cuh.org.uk/addenbrookes/addenbrookes_index.html

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

  1. 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.

  2. 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.

Additional files

Editorial Notes