Study on the Efficacy of Slow Release Insulin in Cystic Fibrosis Patients With Glucide Intolerance and Clinical Decay

Cystic Fibrosis Clinical Trial

Official title:

Phase 3 Study on the Efficacy of Slow Release Insulin in Cystic Fibrosis Patients With Glucide Intolerance and Clinical Decay

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00687466
• Other study ID #: FFC #21/2006
• Secondary ID: eudraCT number 2
• Status: Active, not recruiting
• Phase: Phase 3
• First received: May 27, 2008
• Last updated: August 3, 2009
• Start date: August 2005
• Est. completion date: October 2009

Study information

• Verified date: August 2009
• Source: Fondazione per la ricerca sulla Fibrosi Cistica
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate whether the anticipated use of glargine in CF patients with glucose intolerance may prevent the worsening of nutritional status and pulmonary function.

Description:

Diabetes mellitus may often complicate the cystic fibrosis course, and it is usually preceded by a condition defined as glucose intolerance, during which a significant decay of patient's general conditions is observed. A slow release insulin (glargine) has become available in the market for diabetic patients: its characteristics allow for a single daily dose, and no need of repeated daily monitoring of glycemia.

In this randomized controlled clinical trial we evaluate whether the anticipated use of glargine in CF patients with glucose intolerance may prevent the worsening of nutritional status and pulmonary function.

Eligible patients who will accept to participate to this study will be randomly allocated in the group who will or will not receive glargine as additional supportive therapy. Patients will in any case continue the CF therapy prescribed by their treating physicians and their usual diet. All the patients will be evaluated every three months to assess their nutritional, pulmonary and glycometabolic status. The follow-up will continue until the 18th month after the study entry.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 70 Years

Eligibility

Inclusion Criteria:

• Ascertained diagnosis of CF

• Age = 10 years

• Glucide intolerance: 2 pathologic OGTT ( at 120' glucose value: >140 mg% and <200 mg%) at 2-6 months' interval between each other

• At least one of the following conditions:

• BMI (body mass index) < 10th centile for age and sex (according to Rolland Cachera 1991)

• Loss of one BMI centile class for age and sex in the last year (according to Rolland Cachera 1991)

• FEV1 = 80% of predicted

• FEV1 decrease = 10% in the last year

Exclusion Criteria:

• Specific contraindications for the use of glargine

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Glucose Intolerance

Intervention

Drug:
• Insulin
Insulin Glargine will be administered subcutaneously at the dosage of 0.1 U/Kg/die for three months. In case no hypoglycemic episodes occur during this period, the dosage will be increased to 0.15 U/Kg/die in occasion of the first control (T1) and will be scheduled for other three months. If even during this latter period no cases no hypoglycemic episodes occur, at the second control (T2) the dosage will be increased to the maximum of 0.2/U/Kg/die. It is generally accepted that the final dosage of glargine can be tailored to each patient, but it should be maintained between 0.1 and 0.2 U/Kg/die. Glargine should be administered once daily in the morning and always at the same hour.

Locations

Country	Name	City	State
Italy	Pediatric Department, General Hospital,CF Center	Cerignola (Foggia)
Italy	Ospedale Maggiore Policlinico, Adult CF Center	Milano
Italy	Pediatric Department, Federico II University, Pediatric CF Center	Napoli
Italy	Pediatric Department G.De Cristina Hospital CF Center	Palermo
Italy	Bambino Gesù Hospital CF Center	Roma
Italy	Policlinico Umberto I. CF Center	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione per la ricerca sulla Fibrosi Cistica

Country where clinical trial is conducted

Italy, 

References & Publications (13)

Bismuth E, Laborde K, Taupin P, Velho G, Ribault V, Jennane F, Grasset E, Sermet I, de Blic J, Lenoir G, Robert JJ. Glucose tolerance and insulin secretion, morbidity, and death in patients with cystic fibrosis. J Pediatr. 2008 Apr;152(4):540-5, 545.e1. doi: 10.1016/j.jpeds.2007.09.025. Epub 2007 Nov 26. — View Citation

Bizzarri C, Lucidi V, Ciampalini P, Bella S, Russo B, Cappa M. Clinical effects of early treatment with insulin glargine in patients with cystic fibrosis and impaired glucose tolerance. J Endocrinol Invest. 2006 Mar;29(3):RC1-4. — View Citation

Dobson L, Hattersley AT, Tiley S, Elworthy S, Oades PJ, Sheldon CD. Clinical improvement in cystic fibrosis with early insulin treatment. Arch Dis Child. 2002 Nov;87(5):430-1. — View Citation

Dobson L, Sheldon CD, Hattersley AT. Conventional measures underestimate glycaemia in cystic fibrosis patients. Diabet Med. 2004 Jul;21(7):691-6. — View Citation

Lanng S, Thorsteinsson B, Nerup J, Koch C. Influence of the development of diabetes mellitus on clinical status in patients with cystic fibrosis. Eur J Pediatr. 1992 Sep;151(9):684-7. — View Citation

Lombardo F, De Luca F, Rosano M, Sferlazzas C, Lucanto C, Arrigo T, Messina MF, Crisafulli G, Wasniewska M, Valenzise M, Cucinotta D. Natural history of glucose tolerance, beta-cell function and peripheral insulin sensitivity in cystic fibrosis patients with fasting euglycemia. Eur J Endocrinol. 2003 Jul;149(1):53-9. — View Citation

Mackie AD, Thornton SJ, Edenborough FP. Cystic fibrosis-related diabetes. Diabet Med. 2003 Jun;20(6):425-36. Review. — View Citation

Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):891-5. — View Citation

Moran A, Hardin D, Rodman D, Allen HF, Beall RJ, Borowitz D, Brunzell C, Campbell PW 3rd, Chesrown SE, Duchow C, Fink RJ, Fitzsimmons SC, Hamilton N, Hirsch I, Howenstine MS, Klein DJ, Madhun Z, Pencharz PB, Quittner AL, Robbins MK, Schindler T, Schissel K, Schwarzenberg SJ, Stallings VA, Zipf WB, et al. Diagnosis, screening and management of cystic fibrosis related diabetes mellitus: a consensus conference report. Diabetes Res Clin Pract. 1999 Aug;45(1):61-73. Review. — View Citation

Nousia-Arvanitakis S, Galli-Tsinopoulou A, Karamouzis M. Insulin improves clinical status of patients with cystic-fibrosis-related diabetes mellitus. Acta Paediatr. 2001 May;90(5):515-9. — View Citation

Rafii M, Chapman K, Stewart C, Kelly E, Hanna A, Wilson DC, Tullis E, Pencharz PB. Changes in response to insulin and the effects of varying glucose tolerance on whole-body protein metabolism in patients with cystic fibrosis. Am J Clin Nutr. 2005 Feb;81(2):421-6. — View Citation

Rolon MA, Benali K, Munck A, Navarro J, Clement A, Tubiana-Rufi N, Czernichow P, Polak M. Cystic fibrosis-related diabetes mellitus: clinical impact of prediabetes and effects of insulin therapy. Acta Paediatr. 2001 Aug;90(8):860-7. — View Citation

Solomon MP, Wilson DC, Corey M, Kalnins D, Zielenski J, Tsui LC, Pencharz P, Durie P, Sweezey NB. Glucose intolerance in children with cystic fibrosis. J Pediatr. 2003 Feb;142(2):128-32. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nutritional status evaluated as variations of Z score of BMI		At recruitment time and at +3, +6, +9, +12, +15, +18 months	Yes
Secondary	Glucose tolerance improvement evaluated as improvement of glycometabolic parameter (glycosylated Hb)		At time recruitment and +3,+6,+9+12+15+18 months	Yes