Cystic Fibrosis - Insulin Deficiency, Early Action

Diabetes Clinical Trial

— CF-IDEA  

Official title:

Cystic Fibrosis - Insulin Deficiency, Early Action

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01100892
• Other study ID #: CF-IDEA
• Status: Completed
• Phase: Phase 3
• Start date: December 2010
• Est. completion date: February 2023

Study information

• Verified date: May 2023
• Source: Sydney Children's Hospitals Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Diabetes
• Fibrosis

Intervention

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).

Locations

Country	Name	City	State
Australia	Women's and Children's Hospital	Adelaide	South Australia
Australia	Lady Cilento Children's Hospital	Brisbane	Queensland
Australia	John Hunter Children's Hospital	New Lambton	New South Wales
Australia	Sydney Children's Hospital	Randwick	New South Wales
Australia	Children's Hospital at Westmead	Westmead	New South Wales
United States	Children's Hospital Colorado	Denver	Colorado

Sponsors (5)

Lead Sponsor	Collaborator
Sydney Children's Hospitals Network	Children's Hospital Colorado, John Hunter Children's Hospital, Lady Cilento Children's Hospital, Brisbane, Women's and Children's Hospital, Adelaide

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Weight SDS (Standard Deviation Score)		12 months
Primary	Change in lung function (FEV1, FVC)		12 months
Secondary	Reduced rate of decline in glycaemic category, comparing OGTT at baseline and 12 months.	OGTT = Oral Glucose Tolerance Test	12 months
Secondary	Reduced frequency of hospitalisation for acute respiratory illness		12 months
Secondary	Change in glycaemic status assessed by HbA1c and CGM	CGM = Continuous Glucose Monitoring	12 months
Secondary	Body composition by DEXA. Patients at CHW will also have pQCT.	DEXA = Dual Energy X-ray Absorptiometry; pQCT = peripheral Quantitative Computed Tomography	12 months
Secondary	Change in Grip-strength		12 months
Secondary	Improved quality of life, measured by a validated CF QOL questionnaire		12 months
Secondary	Bacterial colonisation of sputum		12 months
Secondary	Change in effort-dependent lung function: MIP, MEP, SnIP	MIP = Mouth Inspiratory Pressure; MEP = Mouth Expiratory Pressure; SnIP = Sniff Nasal Inspiratory Pressure	12 months