Pasireotide in the Treatment of Hypoglycemia Following Gastric Bypass Surgery

Study Overview
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Brief Summary
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Postprandial hyperinsulinemic hypoglycemia is a well-known and potentially severe complication of Roux-en-Y gastric bypass (RYGB), and the treatment options are limited. Pasireotide has shown to be effective in preventing hypoglycemia in RYGB operated subjects, however treatment often leads to increased hyperglycemia. The purpose of this study is to investigate two doses of pasireotide that are lower than doses previously used in RYGB operated subjects with postprandial hyperinsulinemic hypoglycemia.

Detailed Description
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With the growing number of RYGB operated subjects the attention on complications such as postprandial hyperinsulinemic hypoglycemia (PHH) has increased. PHH is characterized by increased glycemic variability and hypoglycemic episodes occurring 2-3 hours after a meal together with a markedly increase in insulin and glucagon-like-peptide 1 (GLP-1) levels. Symptoms vary from dizziness and palpitations to confusion, loss of consciousness and convulsions. At present there are few treatment options available for RYGB patients with PHH and most of them rely on dietary changes that are difficult to adhere to. Pasireotide has been shown to reduce hypoglycemia in RYGB operated subjects with PHH, but often leads to increased hyperglycemia as well. The purpose of the study is to investigate two doses of pasireotide in RYGB operated subjects with PHH. Each subject will undergo two meal tolerance test (MTT) preceded by either 75 µg or 150 µg of pasireotide. Blood samples will be collected throughout the meal test at predefined time points and will be analyzed for glucose, insulin, C-peptide, GLP-1 and glucagon levels.

Official Title
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Pasireotide in the Treatment of Hypoglycemia Following Gastric Bypass Surgery

Conditions
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Hypoglycemia, Reactive

Intervention / Treatment
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* Drug: Pasireotide 0.3 MG/ML
* Diagnostic Test: Meal tolerance test (MTT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RYGB operated patients with documented hypoglycemia (blood glucose <3.9 mmol/L) who have previously completed the study 'Treatment of hypoglycemia following gastric bypass surgery' (HypoGB2015) Hemoglobin > 7,3 mmol/L Negative human chorionic gonadotropin (hCG) urine test Females of reproductive age: use of safe contraception Exclusion Criteria: Treatment for cardiovascular disease Treatment with antipsychotic medication Treatment for thyroid disease Prior medical treatment of postprandial hyperinsulinemic hypoglycemia Prior allergic reactions to the study medicine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pasireotide75<br>75 micrograms Pasireotide 0.3 MG/ML s.c. before a meal tolerance test (MTT) | Drug: Pasireotide 0.3 MG/ML<br>* See arm description<br>* Other names: Signifor;Diagnostic Test: Meal tolerance test (MTT)<br>* Subjects will consume the liquid meal at baseline and blood will be drawn for continuous blood sampling.<br>|
| Experimental: Pasireotide150<br>150 micrograms Pasireotide 0.3 MG/ML s.c. before a meal tolerance test (MTT) | Drug: Pasireotide 0.3 MG/ML<br>* See arm description<br>* Other names: Signifor;Diagnostic Test: Meal tolerance test (MTT)<br>* Subjects will consume the liquid meal at baseline and blood will be drawn for continuous blood sampling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in glucose (mmol/L) in response to a meal tolerance test (MTT) | Changes in incremental area under the curve (iAUC) for glucose, nadir glucose values, peak glucose values, time spent with glucose values in the hyperglycemic (>7.8 mmol/L) and the hypoglycemic (<3.9 mmol/L) range | From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate | Changes heart rate (beats/min) during the course of a meal tolerance test (MTT) | From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion | 
| Serum insulin levels | Changes in insulin (pmol/L) in response to a meal tolerance test (MTT) | From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion | 
| Serum C-peptide levels | Changes in C-peptide (nmol/L) in response to a meal tolerance test (MTT) | From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion | 
| Plasma glucagon levels | Changes in glucagon (pmol/L) in response to a meal tolerance test (MTT) | From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion | 
| Plasma GLP-1 levels | Changes in glucagon-like peptide 1 (pmol/L) in response to a meal tolerance test (MTT) | From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion | 
| Blood pressure | Changes in blood pressure (mmHg) in response to a meal tolerance test (MTT) | From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric bypass, hypoglycemia, hyperinsulinemia