Sandostatine® LP and Hyperinsulinism

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00987168
First received: September 29, 2009
Last updated: December 18, 2013
Last verified: October 2010

September 29, 2009
December 18, 2013
May 2009
April 2011   (final data collection date for primary outcome measure)
Glycemia > or equal to 3 mmol/L, before and after 4 meals +Midnight + 4 am [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00987168 on ClinicalTrials.gov Archive Site
  • Abdominal ultra echography, before and after 6 month treatment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Life quality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Sandostatine® LP and Hyperinsulinism
Replace Sandostatine® in Three Daily Subcutaneous Injections by a Single Intramuscular Injection of Sandostatine® LP Per Month in Patients With a Diffuse Form of Hyperinsulinism

To replace Sandostatine® in three daily subcutaneous injections by a single intramuscular injection of Sandostatine® LP per month in patients with a diffuse form of hyperinsulinism.

Persistent hyperinsulinemic hypoglycemias of infancy (HI) are characterized by an inappropriate secretion of insulin responsible for profound hypoglycemias which require aggressive treatment to prevent severe and irreversible brain damage.

Thanks to the complementarity and to the synergy between paediatricians, paediatric surgeons, radiologists, pathologists and geneticists, an important stage was reached: the recognition of two clinically similar forms of HI but requiring a radically different treatment: a diffuse form and a focal form in the pancreas.

The medical treatment is based on proglycem, or diazoxide, then octreotide (Sandostatine ®, Novartis) with a dose of 10 to 50 µg/Kg/jour divided to three subcutaneous injections. Most neonates are resistant to diazoxide and side effects are observed (important edema and hypertrichosis). The Sandostatine® is a much more effective treatment, unfortunately with a short half-life and painful injections. In the cases of resistance to the medical treatment, the distinction of the two forms is essential to guide the surgical treatment : partial pancreatectomy in the focal forms, curing definitively hypoglycemia; subtotal pancreatectomy in the diffuse forms resisting to the medical treatment, leading to a diabetes and a pancreatic exocrine insufficiency. Also, the medical treatment is essential in the case of the diffuse forms to avoid a subtotal pancreatectomy. Mutations in two genes encoding the potassium channels, SUR1 and KIR6.2, are responsible for hyperinsulinism resistant to diazoxide.

The Sandostatine® marketed by Novartis exists in two forms, a "rapid" form and a "retarded liberation form". These two molecules have been approved in the treatment of adults in the following indications:

  • Treatment of the clinical symptoms of digestive endocrine tumours
  • Treatment of acromegaly
  • Treatment of primitive thyrotrope adenomata
  • Treatment of unfunctional adenoma
  • Treatment of corticotrope adenoma during (Nelson syndrome) and of functional gonadotrope adenomata
  • After pancreatic surgery
  • Emergency treatment of bleeding secondary to cirrhosis.

Sandostatine® has neither approval for hyperinsulinism, nor in children even though many international publications reported efficacy of treatment by Sandostatine® in hyperinsulinemic children since 1983. Also, by consensus most international teams taking care of hyperinsulinism in infancy propose this treatment to their patients.

Ten children who have a diffuse form of hyperinsulinism have been treated in our department by Sandostatine® given in three subcutaneous injections for several years, in order to avoid a sub-total pancreatectomy. The only possible adverse effect is the appearance of vesicular lithiasis which can be treated by ursodesoxycholic acid . We changed the Sandostatine® treatment of one of our patients by the Sandostatine® LP (retarded liberation form) after written consent of his two parents. Thus we could stop the three injections per day of Sandostatine®. Sandostatine® LP proved to be as efficient on hypoglycemias as the subcutaneous multi-daily injections (SC). The glycemia values were strictly normal, and no hypoglycaemia was observed. Following this observation, we propose to try to substitute the treatment of Sandostatine® given in several subcutaneous injections by one injection of Sandostatine® LP in 10 children followed in the department of Metabolism for hyperinsulinism.

The awaited result of this study is to demonstrate efficacy of Sandostatine® LP and thus replace Sandostatine® in three daily subcutaneous injections by a single intramuscular injection of Sandostatine® LP per month. This study will contribute to an undeniable improvement of the quality of life for the patients and their families.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Congenital Hyperinsulinism
Drug: Sandostatine LP
Intramuscular injection of Sandostatine LP, once per month Dosage : 10 mg, 20 mg, 30 mg
Other Name: Sandostatine LP
Experimental: Sandostatine LP
Intervention: Drug: Sandostatine LP
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
June 2011
April 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • congenital hyperinsulinism patients
  • age of patients : 6 months to 16 years
  • normoglycemia under sandostatine subcutaneous
  • contraception efficiency
  • signed informed consent

Exclusion Criteria:

  • refusal from parents
  • vesicular lithiasis
  • absence of social security
  • hypersensitivity to octreotide or excipients
  • pregnancy or nursing mother
Both
6 Months to 16 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00987168
CRC 07024
Yes
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Novartis
Principal Investigator: Pascale De Lonlay, PUPH Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
October 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP