Hyperinsulinemic Hypoglycemia, Post Gastrointestinal Tract Surgery Hypoglycaemia
Conditions
Brief summary
Somatostatin analogues are a last resort for medical intervention in hyperinsulinemic hypoglycemia (HH). The hypoglycemia is very debilitating and can be even life threatening. There is limited experience with pasireotide in hyperinsulinemic hypoglycemia (only one publication); there is more experience with octreotide, both in adults and children successful interventions with octreotide in hyperinsulinemic hypoglycemia have been published. Pasireotide via its different somatostatin receptor binding profile has clear effects on insulin, glucagon and incretin secretion and can ultimately lead to hyperglycemia. This mode of action (especially the effects on insulin and incretin secretion) could be very useful in the setting of hyperinsulinemic hypoglycemia.
Detailed description
Hyperinsulinemic hypoglycemia as a complication of gastric bypass surgery has been reported to occur between 6 months to 8-10 years after gastric bypass surgery. Although reported as a rare complication from surgery, the incidence is likely higher due to the condition being missed in many patients or being misdiagnosed as dumping syndrome. Unlike dumping syndrome which often presents early in the post-operative course and improves with dietary modification, patients with hyperinsulinemic hypoglycemia have severe postprandial hypoglycemia and sometimes fasting hypoglycemia with symptoms worsening over time despite dietary modification. Calcium stimulation testing often localizes the area of the pancreas where hyperinsulinemia is occurring due to islet cell dysfunction. The pathophysiology of islet cell hypertrophy with Nesidioblastosis is poorly understood. One theory is an increase in glucagon-like peptide-1 (GLP-1) concentration may be responsible for islet cell expansion and subsequent hyperinsulinemic hypoglycemia. Unfortunately, hyperinsulinemia hypoglycemia is incapacitating where patients are restricted from driving, are unable to work, and must always have someone present with glucagon due to the acute severe onset of neuroglycopenia. Surgery to resect the area of the pancreas with Nesidioblastosis has a low success rate of about 60% with many patients developing type 1 diabetes as a result of pancreatic resection. Medical treatment options include calcium channel blockers, Diazoxide, and Octreotide yet patients often fail these treatments as well. Pasireotide would likely be a better option than the current medical therapy available. With Pasireotide, the inhibition of insulin release through inhibiting the somatostatin receptors as well as possible GLP-1 inhibition causing hyperglycemia should reduce hypoglycemic episodes in these patients.
Interventions
DRUGPasireotide
Somatostatin analogues are a last resort for medical intervention in hyperinsulinemic hypoglycemia (HH). The hypoglycemia is very debilitating and can be even life threatening. There is limited experience with pasireotide in hyperinsulinemic hypoglycemia (only one publication); there is more experience with octreotide, both in adults and children and successful interventions with octreotide in hyperinsulinemic hypoglycemia have been published. Pasireotide via its different somatostatin receptor binding profile has clear effects on insulin, glucagon and incretin secretion and can ultimately lead to hyperglycemia. This mode of action (especially the effects on insulin and incretin secretion) could be very useful in the setting of hyperinsulinemic hypoglycemia.
Sponsors
Novartis
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Treatment Plan for an individual patient with pasireotide for Hyperinsulinemic Hypoglycemia (Compassionate Use Protocol for Pasireotide)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients eligible for inclusion in this Treatment Plan have to meet all of the following 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. WHO/ ECOG 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 ULN * INR \< 1.3 * ALT and 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 IMP's ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (e.g., 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
Patients eligible for this Treatment Plan must not meet any of the following criteria: 1. Patients with a known hypersensitivity to somatostatin analogs or any component of the pasireotide LAR or s.c. formulations. 2. Patients with abnormal coagulation (PT or aPTT 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recording of Hypoglycemic events | Up to 2 years | The primary outcome is the number of hypoglycemic events occurring. |
Countries
United States
Outcome results
None listed