Sandostatine® LP and Hyperinsulinism
Condition: Congenital Hyperinsulinism
MeSH terms: Congenital Hyperinsulinism; Nesidioblastosis; Hyperinsulinism
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Sandostatine LP
Intervention type(s): Drug
Intervention description(s): Intramuscular injection of Sandostatine LP, once per month Dosage : 10 mg, 20 mg, 30 mg
Intervention MeSH terms: Octreotide
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Congenital Hyperinsulinism; Hypoglycemia,; Sandostatine subcutaneous in 3 daily injections; Intramuscular injection of Sandostatine® LP per month