Cystic Fibrosis - Insulin Deficiency, Early Action
Condition: Cystic Fibrosis; Diabetes
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional
Phase: Phase 3

Summary: 
      Cystic Fibrosis (CF) is the most common life-threatening genetic condition affecting
      Australian children. As well as repeated lung infections, children with CF develop insulin
      deficiency and eventually diabetes. The CF-IDEA trial (Cystic Fibrosis - Insulin Deficiency,
      Early Action) will determine whether starting insulin treatment before the onset of diabetes
      (earlier than current practice) will improve the health of children with CF by improving body
      weight and lung function.
    

Detailed description: 
      As well as progressive lung disease, patients with Cystic Fibrosis (CF) suffer pancreatic
      destruction, leading to slow but progressive insulin deficiency. Deficiency of insulin, a
      powerful anabolic hormone, causes accelerated decline of weight and lung function (important
      predictors of early mortality in CF).

      We analysed Oral Glucose Tolerance Tests sampled every 30 mins and defined stages of CF
      Insulin Deficiency (CFID) as early glucose abnormalities, CFID1 (BGmax >=8.2 and <11.1mmol/L)
      and CFID2 (BGmax >=11.1 and BG120min <11.1), progressing to diabetes without fasting
      hyperglycaemia (CFID3), and finally to diabetes with fasting hyperglycaemia (CFID4).
      Currently insulin treatment is standard only for CFID3 and 4, but we have data showing that
      the earlier stages (CFID1 and 2) are also associated with declining weight and lung function.

      In the CF-IDEA Trial, subjects with CF aged >=5 years with early glucose abnormalities (CFID1
      or 2) will be randomised to once-daily insulin detemir (Levemir) for 12 months, or to
      observation only. We aim to determine whether starting insulin earlier than current practice
      will prevent decline in weight and lung function, reduce frequency of hospitalisation,
      improve quality of life, and slow progression through CFID categories.

      Our pilot studies using once-daily Levemir in children with CFID1 and 2 found that this
      simple insulin regimen (rather than multiple daily injections) was well accepted by patients,
      with minimal hypoglycaemia, and resulted in significant weight gain and improved lung
      function (compared with 12 months prior to insulin). Sample size calculations for the CF-IDEA
      Trial are based on our pilot studies. When 70-80% of patients have completed the protocol,
      the study statistician will perform an interim analysis (blinded to the other investigators)
      to check the original power calculations.

      Stages of CF Insulin Deficiency:

      CFID1 Peak BG on OGTT >=8.2mmol/L and <11.1mmol/l.

      CFID2 Peak BG on OGTT >=11.1mmol/L and 120 minute BG <11.1.

      CFID3 120 minute BG on OGTT >=11.1mmol/L.

      CFID4 Fasting hyperglycemia (Fasting BG >=7mmol/L).
    

Intervention name(s): Once-daily insulin detemir
Intervention type(s): Drug
Intervention description(s): Insulin detemir is a long-acting insulin analog. Starting dose 0.1 units/kg/day (titrated according to the results of home blood glucose monitoring).
Other intervention name(s): Levemir
Intervention MeSH terms: Insulin Detemir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pediatrics; Pancreas