Clinical trial NCT01100892: Cystic Fibrosis - Insulin Deficiency, Early Action
Official title: Cystic Fibrosis - Insulin Deficiency, Early Action
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Diabetes
Keywords: Pediatrics
Pancreas
Lead sponsor: Sydney Children's Hospitals Network
Sponsor class: OTHER
Collaborators: name: John Hunter Children's Hospital
name: Lady Cilento Children's Hospital, Brisbane
name: Women's and Children's Hospital, Adelaide
name: Children's Hospital Colorado
First posted: 2010-04-09
Enrollment: 100
Sex: ALL
Minimum age (years): 5
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Change in Weight SDS (Standard Deviation Score)
timeFrame: 12 months
measure: Change in lung function (FEV1, FVC)
timeFrame: 12 months
Secondary outcomes:
measure: Reduced rate of decline in glycaemic category, comparing OGTT at baseline and 12 months.
timeFrame: 12 months
measure: Reduced frequency of hospitalisation for acute respiratory illness
timeFrame: 12 months
measure: Change in glycaemic status assessed by HbA1c and CGM
timeFrame: 12 months
measure: Body composition by DEXA. Patients at CHW will also have pQCT.
timeFrame: 12 months
measure: Change in Grip-strength
timeFrame: 12 months
measure: Improved quality of life, measured by a validated CF QOL questionnaire
timeFrame: 12 months
measure: Bacterial colonisation of sputum
timeFrame: 12 months
measure: Change in effort-dependent lung function: MIP, MEP, SnIP
timeFrame: 12 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Lambton
country: Australia
facility: John Hunter Children's Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Children's Hospital at Westmead
state: New South Wales
city: Brisbane
country: Australia
facility: Lady Cilento Children's Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Women's and Children's Hospital
state: South Australia
Study officials:
affiliation: Endocrinology, Sydney Children's Hospital Randwick; School of Women's and Children's Health, University of NSW
name: Charles Verge, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.