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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Sydney Children's Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
The Children's Hospital at Westmead
John Hunter Children's Hospital
Information provided by:
Sydney Children's Hospital
ClinicalTrials.gov Identifier:
NCT01100892
First received: March 31, 2010
Last updated: July 20, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Diabetes
Drug: Once-daily insulin detemir
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Sydney Children's Hospital:

Primary Outcome Measures:
  • Change in Weight SDS (Standard Deviation Score) [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]
  • Change in lung function (FEV1, FVC) [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]
  • Change in Weight SDS (Standard Deviation Score) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in lung function (FEV1, FVC) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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 ]

Secondary Outcome Measures:
  • Reduced rate of decline in glycaemic category, comparing OGTT at baseline and 12 months. [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]
    OGTT = Oral Glucose Tolerance Test

  • Reduced frequency of hospitalisation for acute respiratory illness [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]
  • Change in glycaemic status assessed by HbA1c and CGM [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]
    CGM = Continuous Glucose Monitoring

  • Body composition by DEXA. Patients at CHW will also have pQCT. [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]

    DEXA = Dual Energy X-ray Absorptiometry

    pQCT = peripheral Quantitative Computed Tomography


  • Change in Grip-strength [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]
  • Improved quality of life, measured by a validated CF QOL questionnaire [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]
  • Bacterial colonisation of sputum [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]
  • Change in effort-dependent lung function: MIP, MEP, SnIP [ Time Frame: 0 months (baseline) ] [ Designated as safety issue: No ]

    MIP = Mouth Inspiratory Pressure

    MEP = Mouth Expiratory Pressure

    SnIP = Sniff Nasal Inspiratory Pressure


  • Change in glycaemic status assessed by HbA1C and CGM [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    CGM continuous glucose monitoring

  • Change in Grip-Strength [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in effort-dependent lung function: MIP, MEP, SnIP [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    MIP = Mouth Inspiratory Pressure

    MEP = Mouth Expiratory Pressure

    SnIP = Sniff Nasal Inspiratory Pressure


  • Change in glycaemic status assessed by HbA1c [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Body composition by DEXA. Patients at CHW will also have pQCT. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 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 ]
  • 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 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


Estimated Enrollment: 100
Study Start Date: December 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Levemir

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 >=8 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).

  Eligibility

Ages Eligible for Study:   8 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with CF aged >=8 yrs attending Sydney Children's Hospital (SCH), Children's Hospital Westmead (CHW), or John Hunter Children's Hospital (JHCH).
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01100892

Contacts
Contact: Shihab Hameed, BSc(Med)MBBS(Hons) +61 2 9382 1456 shihab.hameed@sesiahs.health.nsw.gov.au
Contact: Charles Verge, MBBS, FRACP, PhD +61 2 9382 1456 charles.verge@sesiahs.health.nsw.gov.au

Locations
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    Charles.Verge@SESIAHS.health.NSW.gov.au   
Contact: Shihab Hameed    93821456    Shihab.Hameed@SESIAHS.health.NSW.gov.au   
Children's Hospital at Westmead Not yet recruiting
Westmead, New South Wales, Australia, 2145
Contact: Hiran Selvadurai         
Contact: Peter Cooper         
Sponsors and Collaborators
Sydney Children's Hospital
The Children's Hospital at Westmead
John Hunter Children's Hospital
Investigators
Principal Investigator: Charles F Verge, MBBS; PhD Endocrinology, Sydney Children's Hospital; School of Women's and Children's Health, University of NSW
  More Information

Publications:
Responsible Party: Dr Charles Verge, Endocrinology, Sydney Children's Hospital
ClinicalTrials.gov Identifier: NCT01100892     History of Changes
Other Study ID Numbers: CF-IDEA
Study First Received: March 31, 2010
Last Updated: July 20, 2011
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by Sydney Children's Hospital:
Pediatrics
Pancreas

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Insulin
Insulin, Globin Zinc
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014