Congenital Hyperinsulinism
Conditions
Keywords
hyperinsulinemia, hypoglycemia, somatostatin, pasireotide, congenital
Brief summary
Congenital hyperinsulinism is a rare condition that can cause life-threatening hypoglycemia. Current treatment for congenital hyperinsulinism is often suboptimal, and such individuals may respond to a new somatostatin analog, pasireotide. This is a compassionate use study of the effects of pasireotide on individuals with suboptimally treated congenital hyperinsulinism.
Detailed description
Congenital hyperinsulinism is a rare condition that can cause life-threatening hypoglycemia. Current treatment for congenital hyperinsulinism is often suboptimal, with diazoxide as the mainstay of treatment. Individuals who are not adequately treated with diazoxide may undergo pancreatectomy. Octreotide has been used with some success in congenital hyperinsulinism but there is limited data on pasireotide, the newest somatostatin receptor agonist, which, compared to octreotide, has 30-40 times greater affinity for somatostatin receptors 1 (SSTR1) and 5 (SSTR5), 5 times greater for somatostatin receptor 3 (SSTR3) and a comparable affinity for somatostatin receptor 2 (SSTR2). In human islets, SSTR2 & SSTR5 are present in beta cells. Therefore, there is reason to believe that pasireotide may have greater effectiveness than octreotide in preventing hypoglycemia due to hyperinsulinism. Indeed hyperglycemia is a known effect of pasireotide when used for treatment of Cushing's disease and Acromegaly. The current study is of compassionate use for prevention of hypoglycemia in individuals with congenital hyperinsulinemic hypoglycemia who are not adequately treated with diazoxide.
Interventions
DRUGPasireotide
Sponsors
Montefiore Medical Center
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Inclusion criteria
1. Male or female patients aged 18 years or older 2. Patients with a confirmed diagnosis of hyperinsulinemic hypoglycemia, if possible by genetic testing 3. Patients not controlled by medical therapies (e.g. diazoxide or octreotide) and/or pancreatic surgery or patients not eligible for surgery 4. World Health Organization/ Eastern Cooperative Oncology Group Performance Status of 0-2. 5. Life expectancy ≥12 weeks 6. Adequate end organ function as defined by: No evidence of significant liver disease: * Serum total bilirubin ≤1.5 x upper limit of normal (ULN) * International Normalized Ratio (INR) \< 1.3 * Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2 x ULN, * Alkaline phosphatase ≤ 2.5 x ULN 7. Written informed consent obtained prior to treatment to be consistent with local regulatory requirements 8. Is suffering from a serious or life-threatening disease or condition 9. Does not have access to a comparable or satisfactory alternative treatment (i.e., comparable or satisfactory treatment is not available or does not exist) 10. Is not eligible for participation in any of the investigators ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (for example., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient 11. There are meaningful human clinical data to support an assessment that the potential benefits to patient outweigh risks. 12. Meets any other relevant medical criteria for compassionate use of the investigational product 13. Is not being transferred from an ongoing clinical trial for which they are still eligible
Exclusion criteria
1. Patients with a known hypersensitivity to somatostatin analogs or any component of the pasireotide long acting release (LAR) or subcutaneous. formulations. 2. Patients with abnormal coagulation (prothrombin time or activated partial thromboplastin time elevated by 30% above normal limits). 3. Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion. 4. Patients currently using warfarin / warfarin derivatives 5. Patients with symptomatic cholelithiasis. 6. Patients who are not biochemically euthyroid. Patients with known history of hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy for at least 3 months. 7. QT-related
Countries
United States
Outcome results
None listed