Cystic Fibrosis - Insulin Deficiency, Early Action (CF-IDEA)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Cystic Fibrosis - Insulin Deficiency, Early Action|
- Change in Weight SDS (Standard Deviation Score) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Change in lung function (FEV1, FVC) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Reduced rate of decline in glycaemic category, comparing OGTT at baseline and 12 months. [ Time Frame: 12 months ] [ Designated as safety issue: No ]OGTT = Oral Glucose Tolerance Test
- Reduced frequency of hospitalisation for acute respiratory illness [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Change in glycaemic status assessed by HbA1c and CGM [ Time Frame: 12 months ] [ Designated as safety issue: No ]CGM = Continuous Glucose Monitoring
- Body composition by DEXA. Patients at CHW will also have pQCT. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
DEXA = Dual Energy X-ray Absorptiometry
pQCT = peripheral Quantitative Computed Tomography
- Change in Grip-strength [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Improved quality of life, measured by a validated CF QOL questionnaire [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Bacterial colonisation of sputum [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Change in effort-dependent lung function: MIP, MEP, SnIP [ Time Frame: 12 months ] [ Designated as safety issue: No ]
MIP = Mouth Inspiratory Pressure
MEP = Mouth Expiratory Pressure
SnIP = Sniff Nasal Inspiratory Pressure
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
No Intervention: Control group
Observation only. Does not receive once-daily insulin detemir.
Experimental: Once-daily insulin detemir
Once-daily insulin detemir
Drug: Once-daily insulin detemir
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 Name: Levemir
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01100892
|Contact: Shihab Hameed, BSc(Med)MBBS||+61 2 9382 1456||s.hameed@UNSW.edu.au|
|Contact: Charles Verge, MBBS PhD||+61 2 9382 1456||c.verge@UNSW.edu.au|
|Australia, New South Wales|
|John Hunter Children's Hospital||Recruiting|
|New Lambton, New South Wales, Australia, 2310|
|Contact: Jodi Hilton|
|Contact: Patricia Crock|
|Sydney Children's Hospital||Recruiting|
|Randwick, New South Wales, Australia, 2031|
|Contact: Charles Verge 93821456 c.verge@UNSW.edu.au|
|Contact: Shihab Hameed 93821456 s.hameed@UNSW.edu.au|
|Children's Hospital at Westmead||Recruiting|
|Westmead, New South Wales, Australia, 2145|
|Contact: Hiran Selvadurai|
|Contact: Peter Cooper|
|Lady Cilento Children's Hospital||Recruiting|
|Brisbane, Queensland, Australia, 4101|
|Contact: Claire Wainwright|
|Contact: Joyce Cheney|
|Australia, South Australia|
|Women's and Children's Hospital||Recruiting|
|Adelaide, South Australia, Australia, 5006|
|Contact: Andrew Tai|
|Contact: Alexia Pena|
|Principal Investigator:||Charles Verge, MBBS PhD||Endocrinology, Sydney Children's Hospital Randwick; School of Women's and Children's Health, University of NSW|