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
  Purpose

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.


Condition Intervention Phase
Congenital Hyperinsulinism
Drug: Sandostatine LP
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Glycemia > or equal to 3 mmol/L, before and after 4 meals +Midnight + 4 am [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 10
Study Start Date: May 2009
Study Completion Date: June 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sandostatine LP Drug: Sandostatine LP
Intramuscular injection of Sandostatine LP, once per month Dosage : 10 mg, 20 mg, 30 mg
Other Name: Sandostatine LP

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   6 Months to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00987168

Locations
France
Necker Hospital
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Novartis
Investigators
Principal Investigator: Pascale De Lonlay, PUPH Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00987168     History of Changes
Other Study ID Numbers: CRC 07024
Study First Received: September 29, 2009
Last Updated: December 18, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Congenital Hyperinsulinism
Hypoglycemia,
Sandostatine subcutaneous in 3 daily injections
Intramuscular injection of Sandostatine® LP per month

Additional relevant MeSH terms:
Hyperinsulinism
Congenital Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Infant, Newborn, Diseases
Hypoglycemia
Octreotide
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 22, 2014