Cystic Fibrosis - Insulin Deficiency, Early Action

Phase 3

Completed

• Conditions: Cystic Fibrosis; Diabetes
• Interventions: Drug: Once-daily insulin detemir

• Registration Number: NCT01100892
• Lead Sponsor: Sydney Children's Hospitals Network

Brief 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).

Study Timeline

• Study First Submitted: 2010-03-31
• Study First Submitted QC: 2010-04-08
• Study First Posted: 2010-04-09
• Study Start: 2010-12
• Primary Completion: 2023-02
• Study Completion: 2023-02
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-29
• Last Update Posted: 2023-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Patients with CF aged >=5 yrs attending one of the study sites.
• CFID1 or CFID2 (defined as BGmax >=8.2 and BG120 <11.1mmol/l on OGTT performed within the last 6 months, when respiratory function stable as judged by the treating respiratory team, not taking fluoroquinolone antibiotics, and not taking systemic glucocorticoids).

Exclusion Criteria

• Cystic Fibrosis Related Diabetes, defined as CFID3 (BG120 >11.1mmol/L) or CFID4 (fasting BG >7mmol/L). Such patients will be offered insulin treatment as standard clinical care.
• Unstable respiratory disease (hospital admission for treatment of respiratory exacerbation within the last month).
• Treatment with systemic glucocorticoids of more than 1 month duration, within the last 12 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Once-daily insulin detemir	Once-daily insulin detemir	Once-daily insulin detemir

Primary Outcome Measures

Name	Time	Method
Change in lung function (FEV1, FVC)	12 months
Change in Weight SDS (Standard Deviation Score)	12 months

Secondary Outcome Measures

Name	Time	Method
Change in Grip-strength	12 months
Improved quality of life, measured by a validated CF QOL questionnaire	12 months
Body composition by DEXA. Patients at CHW will also have pQCT.	12 months	DEXA = Dual Energy X-ray Absorptiometry; pQCT = peripheral Quantitative Computed Tomography
Reduced frequency of hospitalisation for acute respiratory illness	12 months
Change in glycaemic status assessed by HbA1c and CGM	12 months	CGM = Continuous Glucose Monitoring
Reduced rate of decline in glycaemic category, comparing OGTT at baseline and 12 months.	12 months	OGTT = Oral Glucose Tolerance Test
Bacterial colonisation of sputum	12 months
Change in effort-dependent lung function: MIP, MEP, SnIP	12 months	MIP = Mouth Inspiratory Pressure; MEP = Mouth Expiratory Pressure; SnIP = Sniff Nasal Inspiratory Pressure

Trial Locations

Locations (6)

Sydney Children's Hospital; 🇦🇺 Randwick, New South Wales, Australia

Lady Cilento Children's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Children's Hospital Colorado; 🇺🇸 Denver, Colorado, United States

Women's and Children's Hospital; 🇦🇺 Adelaide, South Australia, Australia

John Hunter Children's Hospital; 🇦🇺 New Lambton, New South Wales, Australia

Children's Hospital at Westmead; 🇦🇺 Westmead, New South Wales, Australia