Cystic Fibrosis - Insulin Deficiency, Early Action

NCT ID: NCT01100892

Last Updated: 2023-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2023-02-28

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).

Conditions

Cystic Fibrosis; Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control group

Observation only. Does not receive once-daily insulin detemir.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Once-daily insulin detemir

Once-daily insulin detemir

Group Type: EXPERIMENTAL

Once-daily insulin detemir

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

Levemir

Eligibility Criteria

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

John Hunter Children's Hospital

OTHER

Sponsor Role: collaborator

Lady Cilento Children's Hospital, Brisbane

OTHER

Sponsor Role: collaborator

Women's and Children's Hospital, Adelaide

UNKNOWN

Sponsor Role: collaborator

Children's Hospital Colorado

OTHER

Sponsor Role: collaborator

Sydney Children's Hospitals Network

OTHER

Sponsor Role: lead

Responsible Party

Dr Charles Verge

Head of Endocrinology, Sydney Children's Hospital, Randwick

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Charles Verge, MBBS PhD

Role: PRINCIPAL_INVESTIGATOR

Endocrinology, Sydney Children's Hospital Randwick; School of Women's and Children's Health, University of NSW

Locations

Children's Hospital Colorado

Denver, Colorado, United States

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, Australia

Lady Cilento Children's Hospital

Brisbane, Queensland, Australia

Women's and Children's Hospital

Adelaide, South Australia, Australia

Countries

United States; Australia

References

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.

Reference Type: BACKGROUND

PMID: 19910502 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21493664 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21626717 (View on PubMed)

Hameed S, Barnes EH, Briody J, Wainwright CE, Hilton J, Field PI, Tai A, Belessis Y, Chan CL, Selvadurai H, Prentice B, Katz T, McMahon SK, Neylan M, Pena A, Jaffe A, Verge CF. Insulin for early glycaemic abnormality in children with cystic fibrosis without cystic fibrosis-related diabetes (CF-IDEA): a randomised controlled trial. Lancet Child Adolesc Health. 2025 Jun;9(6):371-382. doi: 10.1016/S2352-4642(25)00099-9.

Reference Type: DERIVED

PMID: 40379429 (View on PubMed)

Other Identifiers

CF-IDEA

Identifier Type: -

Identifier Source: org_study_id