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Treatment of Hypoglycemia Following Gastric Bypass Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02527993
Recruitment Status : Completed
First Posted : August 19, 2015
Last Update Posted : March 7, 2018
Sponsor:
Information provided by (Responsible Party):
Caroline Christfort Øhrstrøm, Zealand University Hospital

Brief Summary:

Obesity is increasing worldwide and consequently the need for efficient treatment opportunities. Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed bariatric procedures used in the treatment of severe obesity. The surgery results in significant and sustained weight loss and has a beneficial effect on blood glucose regulation.

However, some patients experience the syndrome postprandial hyperinsulinemic hypoglycemia years after the operation, with symptoms varying from mild dizziness to confusion, loss of consciousness and seizures. Larger insulin and glucagon-like peptide 1 (GLP-1) responses to an oral glucose load are believed to play a role in the syndrome, which is not yet fully understood. There are no current treatment guidelines beside dietary recommendations.

The purpose of this study is to compare different pharmacological treatments on daily blood glucose variations as well as postprandial hormonal and autonomous changes in subjects with symptoms of postprandial hyperinsulinemic hypoglycemia after RYGB.


Condition or disease Intervention/treatment Phase
Hypoglycemia Obesity Surgery Drug: Glucobay (acarbose) Drug: Januvia (sitagliptin) Drug: Verapamil HEXAL (verapamil) Drug: Victoza (liraglutide) Drug: Signifor (pasireotide) Device: Continuous glucose monitoring (CGM) Dietary Supplement: Meal tolerance test (MTT) Phase 4

Detailed Description:

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed bariatric procedures used in the treatment of severe obesity. RYGB has in several studies been shown to result in significant and sustained weight loss. Moreover, RYGB has a beneficial effect on obese subjects with type 2 diabetes by improving blood glucose regulation, resulting in remission or partial remission of type 2 diabetes already days after surgery.

The changes of the anatomy of the stomach and small intestine cause a faster and more abrupt increase in blood glucose after a meal. As a consequence of the changed glucose absorption after RYGB and the increased insulin secretion, some subjects experience the condition named postprandial hyperinsulinemic hypoglycemia. Postprandial hyperinsulinemic hypoglycemia is typically seen years after RYGB and the symptoms vary from mild dizziness to confusion, loss of consciousness and seizures. The condition is characterized by large postprandial blood glucose variations accompanied by exaggerated insulin and glucagon-like peptide 1 (GLP-1) responses. Continuous glucose monitoring (CGM) have shown that subjects suffering from postprandial hyperinsulinemic hypoglycemia presents large variations in blood glucose from values below 3.5 mmol/L to diabetic values above 11.1 mmol/L within the first hour after a meal.

At present, there are no treatment guidelines beside dietary recommendations. Experimental treatment includes diet modifications, pharmaceutical treatments and surgical procedures. Several pharmaceutical agents have been attempted in the management of postprandial hyperinsulinemic hypoglycemia, but overall the existing studies consist of few case reports and case series evaluated primarily by relief of symptoms and not by CGM and hormonal analyses.

The study is designed as a randomized, non-blinded cross-over study including five treatment arms. The pharmaceutical agents are: a) Glucobay, b) Januvia, c) Verapamil, d) Victoza and e) Signifor. The treatment duration is 1 - 3 weeks, except for Signifor, which is administered for one day only. Each treatment period is separated by a wash out period of 7-10 days.

Sixteen none diabetic women are included in the study. They have undergone RYGB and have symptoms of postprandial hyperinsulinemic hypoglycemia. Moreover, former CGM has shown fluctuations in blood glucose of more than 5 mmol/L during daily living and with at least one blood glucose reading below 3.5 mmol/L.

Six days continuous glucose monitoring will be performed at run-in and during each treatment arm, except for e) Signifor due to the short treatment period. At the end of the CGM measurement a meal tolerance test (MTT) will be performed. During the MTT blood samples for glucose measurements and hormone assessments (insulin, C-peptide, GLP-1, gastric inhibitory peptide (GIP), glucagon, insulin like growth factor (IGF-1), epinephrine, norepinephrine) will be drawn continuously as well as continuous pulse recording and blood pressure measurements.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Hypoglycemia Following Gastric Bypass Surgery
Study Start Date : October 2015
Actual Primary Completion Date : April 8, 2017
Actual Study Completion Date : April 8, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia

Arm Intervention/treatment
Experimental: Glucobay
Tablet Glucobay (acarbose) 50 mg x 6 daily for 7 days.
Drug: Glucobay (acarbose)
Se arm description
Other Name: glucobay

Device: Continuous glucose monitoring (CGM)
Continuous glucose monitoring will be performed during 6 days of the treatment period.

Dietary Supplement: Meal tolerance test (MTT)
A meal tolerance test will be performed at the end of the treatment period. The subjects will consume the liquid meal at baseline and blood will be drawn for continuous blood sampling.

Experimental: Januvia
Tablet Januvia (sitagliptin) 100 mg orally O.D for 7 days.
Drug: Januvia (sitagliptin)
Se arm description
Other Name: Januvia

Device: Continuous glucose monitoring (CGM)
Continuous glucose monitoring will be performed during 6 days of the treatment period.

Dietary Supplement: Meal tolerance test (MTT)
A meal tolerance test will be performed at the end of the treatment period. The subjects will consume the liquid meal at baseline and blood will be drawn for continuous blood sampling.

Experimental: Verapamil
Tablet Verapamil 120 mg orally O.D for 7 days.
Drug: Verapamil HEXAL (verapamil)
Se arm description
Other Name: Verapamil HEXAL

Device: Continuous glucose monitoring (CGM)
Continuous glucose monitoring will be performed during 6 days of the treatment period.

Dietary Supplement: Meal tolerance test (MTT)
A meal tolerance test will be performed at the end of the treatment period. The subjects will consume the liquid meal at baseline and blood will be drawn for continuous blood sampling.

Experimental: Victoza
Subcutaneous injection of Victoza (liraglutide) 0,6-1,2 mg O.D for three weeks.
Drug: Victoza (liraglutide)
Se arm description
Other Name: Victoza

Device: Continuous glucose monitoring (CGM)
Continuous glucose monitoring will be performed during 6 days of the treatment period.

Dietary Supplement: Meal tolerance test (MTT)
A meal tolerance test will be performed at the end of the treatment period. The subjects will consume the liquid meal at baseline and blood will be drawn for continuous blood sampling.

Experimental: Signifor
Subcutaneous injection of Signifor (pasireotide) 300 µg as a single dose prior to a meal tolerance test.
Drug: Signifor (pasireotide)
Se arm description
Other Name: Signifor

Dietary Supplement: Meal tolerance test (MTT)
A meal tolerance test will be performed at the end of the treatment period. The subjects will consume the liquid meal at baseline and blood will be drawn for continuous blood sampling.




Primary Outcome Measures :
  1. Changes in blood glucose (mmol/L) assessed by continuous glucose monitoring (CGM). [ Time Frame: 6 days CGM will be performed at week 1, 3, 5, 7 and 11. ]

Secondary Outcome Measures :
  1. Changes in glucose (mmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  2. Changes heart rate (beats/min) during the course of a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  3. Changes in insulin (pmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  4. Changes in C-peptide (nmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  5. Changes in Insulin-like growth factor 1 (nmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  6. Changes in glucagon (pmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  7. Changes in glucagon-like peptide 1 (pmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  8. Changes in gastric inhibitory peptide (pmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  9. Changes in epinephrine (pmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]
  10. Changes in norepinephrine (pmol/L) in response to a meal tolerance test (MTT) [ Time Frame: From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion. ]


Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   25 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • symptoms of postprandial hyperinsulinemic hypoglycemia.
  • fluctuations in blood glucose of more than 5 mmol/L during daily living
  • at least one blood glucose reading below 3.5 mmol/L.
  • More than 18 months since RYGB
  • HbA1c < 40 mmol/L
  • Hemoglobin > 7,3 mmol/L
  • Ferritin > 30 µg/L
  • Cobalamin > 150 picomol/L
  • Creatinine < 105 mmol/L
  • C peptide > 1,0 nmol/L
  • Insulin > 35 pmol/L
  • Normal EKG
  • Negative human chorionic gonadotropin (hCG) urine test
  • Females of reproductive age: use of safe contraception

Exclusion Criteria:

  • Treatment for cardiovascular disease
  • Treatment with antipsychotics, antidepressants or anxiolytics
  • Smoking
  • Treatment for thyroid disease
  • Prior medical treatment of postprandial hyperinsulinemic hypoglycemia
  • Allergy for the study medicine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527993


Sponsors and Collaborators
Zealand University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Caroline C Gormsen, M.D. Department of Internal Medicine, Koege University Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Caroline Christfort Øhrstrøm, MD, clinical assistant, Zealand University Hospital
ClinicalTrials.gov Identifier: NCT02527993    
Other Study ID Numbers: HypoGB2015
First Posted: August 19, 2015    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: March 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Sitagliptin Phosphate
Liraglutide
Acarbose
Verapamil
Pasireotide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycoside Hydrolase Inhibitors
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents