Pasireotide in the Treatment of Hypoglycemia Following Gastric Bypass Surgery

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.

Study Overview

• Status: Unknown
• Conditions: Hypoglycemia, Reactive
• Intervention / Treatment: Drug: Pasireotide 0.3 MG/ML; Diagnostic test: Meal tolerance test (MTT)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Køge, Denmark, 4600
    • Zealand University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zealand University Hospital
• Investigators: Principal Investigator: Caroline C Øhrstrøm, MD, Department of Medicine, Zealand University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): November 1, 2018

Study Registration Dates

• First Submitted: April 19, 2018
• First Submitted That Met QC Criteria: April 19, 2018
• First Posted (Actual): May 2, 2018

Study Record Updates

• Last Update Posted (Actual): July 5, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: hypoglycemia; gastric bypass; hyperinsulinemia
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: PasHypo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No