Congenital Hyperinsulinism Clinical Trial
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
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.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT02021604 -
Fluorodopa F 18 in Congenital Hyperinsulinism and Insulinoma
|
Phase 1 | |
Recruiting |
NCT04732416 -
HM15136 Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI)
|
Phase 2 | |
Completed |
NCT02937558 -
CSI-Glucagon for Prevention of Hypoglycemia in Children With Congenital Hyperinsulinism
|
Phase 2 | |
Completed |
NCT02604485 -
A Single-Dose Open-Label Study of XOMA 358 in Subjects With Congenital Hyperinsulinism
|
Phase 2 | |
Recruiting |
NCT04205604 -
18FluoroLDOPA PET Imaging for the Detection and Localization of Focal Congenital Hyperinsulinism
|
Phase 2 | |
Completed |
NCT00897676 -
Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT03941236 -
Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon in Children With Congenital Hyperinsulinism
|
Phase 3 | |
Completed |
NCT03042416 -
18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety
|
Phase 3 | |
Completed |
NCT04172441 -
Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism
|
Phase 2/Phase 3 | |
Recruiting |
NCT04706910 -
18F-DOPA II - PET Imaging Optimization
|
Phase 3 | |
Recruiting |
NCT06208215 -
RZ358 Treatment for Congenital Hyperinsulinism
|
Phase 3 | |
Completed |
NCT03777176 -
A Two-Period Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism
|
Phase 3 | |
Recruiting |
NCT03768518 -
GLP-1 Receptor Expression in CHI
|
||
Completed |
NCT04538989 -
An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism
|
Phase 2 | |
Completed |
NCT01070758 -
Lanreotide Autogel Treatment of Patients With Congenital Hyperinsulinism of Infancy
|
Phase 4 | |
Completed |
NCT00674440 -
Utility of [F-18] fluoroDOPA for Neonatal Hyperinsulinism
|
Phase 2 | |
Terminated |
NCT00835328 -
Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia
|
Phase 1/Phase 2 | |
Completed |
NCT00571324 -
Effect of Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism
|
Phase 1/Phase 2 | |
Withdrawn |
NCT03053284 -
Pasireotide in Hyperinsulinemic Hypoglycemia
|
Phase 2 | |
No longer available |
NCT02533219 -
Study of the Use of [18F]-DOPA in Hyperinsulinemic Hypoglycemia
|