Cystic Fibrosis - Insulin Deficiency, Early Action (CF-IDEA)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes; Cystic Fibrosis
• Intervention / Treatment: Drug: Once-daily insulin detemir

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia, 2310
      • John Hunter Children's Hospital
    • Randwick, New South Wales, Australia, 2031
      • Sydney Children's Hospital
    • Westmead, New South Wales, Australia, 2145
      • Children's Hospital at Westmead
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Lady Cilento Children's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital
• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Observation only. Does not receive once-daily insulin detemir.
Experimental: 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 Names: Levemir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Weight SDS (Standard Deviation Score)	12 months
Change in lung function (FEV1, FVC)	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sydney Children's Hospitals Network
• Collaborators: Children's Hospital Colorado; Women's and Children's Hospital, Adelaide; John Hunter Children's Hospital; Lady Cilento Children's Hospital, Brisbane
• Investigators: Principal Investigator: Charles Verge, MBBS PhD, Endocrinology, Sydney Children's Hospital Randwick; School of Women's and Children's Health, University of NSW

Publications and helpful links

General Publications

• Hameed S, Morton JR, Jaffe A, Field PI, Belessis Y, Yoong T, Katz T, Verge CF. Early glucose abnormalities in cystic fibrosis are preceded by poor weight gain. Diabetes Care. 2010 Feb;33(2):221-6. doi: 10.2337/dc09-1492. Epub 2009 Nov 12.
• Hameed S, Morton JR, Field PI, Belessis Y, Yoong T, Katz T, Woodhead HJ, Walker JL, Neville KA, Campbell TA, Jaffe A, Verge CF. Once daily insulin detemir in cystic fibrosis with insulin deficiency. Arch Dis Child. 2012 May;97(5):464-7. doi: 10.1136/adc.2010.204636. Epub 2011 Apr 14.
• Hameed S, Jaffe A, Verge CF. Cystic fibrosis related diabetes (CFRD)--the end stage of progressive insulin deficiency. Pediatr Pulmonol. 2011 Aug;46(8):747-60. doi: 10.1002/ppul.21495. Epub 2011 May 27.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2010
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: April 8, 2010
• First Posted (Estimated): April 9, 2010

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 29, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Pediatrics; Pancreas
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Detemir
• Other Study ID Numbers: CF-IDEA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO