CLOuD

Closed Loop from Onset in type 1 Diabetes

 

Research summary

Management of newly diagnosed T1D in children and adolescents is challenging for patients, families, carers, and health care professionals. Glucose is the dominant metabolic substrate for brain function and the glycaemic instability inherent in TID is known to affect brain structure and function in those with poorly controlled disease. Severe hypoglycaemia, particularly nocturnal episodes, is more common in children and has a negative impact on the developing brain. Fear of hypoglycaemia is common, impacts quality of life and psychological well-being of the young and their families, and leads to suboptimal glucose control. Glycaemic control usually deteriorates during adolescence. The Diabetes Control and Complications Trial (DCCT) revealed both higher HbA1c levels and a 50% increase in the rate of severe hypoglycaemia in intensively treated adolescents compared to adults. Teenagers with T1D face the burden of diabetes management in addition to major physiological and psychological changes accompanying puberty.

A potential key benefit of closed-loop insulin delivery is the retention of residual C-peptide secretion which has been shown to decrease the risk of microvascular complications and a lower risk of severe hypoglycaemia by 65% when compared to intensively treated participants without residual beta-cell function in the DCCT trial. Thus the most important long term impact of improved glucose control and residual islet function may be reduced rates of diabetes complications and improved quality of life.

The study builds on recent technological advances of closed-loop insulin delivery (artificial pancreas). The purpose of this study is to test the impact of continued intensive metabolic control using closed-loop insulin delivery after diagnosis on preservation of C-peptide residual secretion. The study enrols children aged 10 and older, as they are characterised by higher residual C-peptide secretion at diagnosis compared to younger children. The present study will also test the feasibility and acceptance of this therapy so that it could be considered as a standard treatment modality in the future.

The primary objective is to evaluate the effect of continued intensive metabolic control using closed-loop insulin delivery after diagnosis on preservation of C-peptide residual secretion by comparing the area under the stimulated C-peptide curve (AUC) of a mixed meal glucose tolerance test conducted at the 12-month visit in participants receiving closed-loop insulin delivery with those receiving standard therapy, i.e. multiple daily injections applying basal-bolus regimen.

clinicaltrials.gov

Main inclusion criteria

  1. Diagnosis of type 1 diabetes within previous ten working days. Day 1 will be defined as the day insulin was first administered. Type 1 diabetes will be defined according to WHO criteria using standard diagnostic practice.

    1. [WHO definition: ‘The aetiological type named type 1 encompasses the majority of cases with are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).’]

  2. The subject is at least 10 years and not older than 17.9 years

  3. The subject/carer is willing to perform regular capillary blood glucose monitoring, with at least 4 blood glucose measurements taken every day

  4. The subject is literate in English

  5. The subject is willing to wear glucose sensor

  6. The subject is willing to wear closed loop system at home

  7. The subject is willing to follow study specific instructions

  8. The subject is willing to upload pump and CGM data at regular intervals

Main exclusion criteria

  1. Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator

  2. Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, nonselective beta-blockers and MAO inhibitors etc.

  3. Known or suspected allergy to insulin

  4. Regular use of acetaminophen

  5. Lack of reliable telephone facility for contact

  6. Pregnancy, planned pregnancy, or breast feeding

  7. Living alone

  8. Severe visual impairment

  9. Severe hearing impairment

  10. Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement

  11. Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located at places of the body, which potentially are possible to be used for localisation of the glucose sensor

  12. Illicit drugs abuse

  13. Prescription drugs abuse

  14. Alcohol abuse

  15. Sickle cell disease, haemoglobinopathy; receiving red blood cell transfusion or erythropoietin within 3 months prior to time of screening

  16. Eating disorder such as anorexia or bulimia

  17. Milk protein allergy

Chief investigator

Dr Roman Hovorka

Contact details

Clinical Trials Manager: Dr Paula Kareclas

Telephone: 01223 254917 | Email: [email protected]