Forecasting and Preventing Post-Bariatric Hypoglycaemia WP 2 (PBH Forecast)

Forecasting and Preventing Post-Bariatric Hypoglycaemia (Work Package 2)

The overall aim of this study is to develop a sustainable hypoglycemia correction strategy.

Study Overview

• Status: Completed
• Conditions: Post-bariatric Hypoglycaemia; Roux-en-Y Gastric Bypass
• Intervention / Treatment: Other: 15 g dextrose; Other: 5 g dextrose; Other: Protein bar

Detailed Description

Obesity is a major global public health concern, for which the most effective therapy is bariatric surgery. Beyond weight loss, bariatric surgery exerts powerful effects on glucose metabolism, achieving complete type 2 diabetes remission in up to 70% of cases. An exaggeration of these effects, however, can result in an increasingly recognized metabolic complication known as postprandial hyperinsulinaemic hypoglycaemia or post-bariatric hypoglycaemia (PBH). The condition manifests 1-3 years after surgery with meal-induced hypoglycaemic episodes. Emerging data suggests that PBH is more frequent than previously thought and affects approximately 30% of postoperative patients, more commonly after gastric bypass than sleeve gastrectomy. Of note, asymptomatic PBH is common, as shown in studies using continuous glucose monitoring (CGM). It is known from extensive research in people with diabetes that recurrent episodes of hypoglycaemia impair counter regulatory defences against subsequent events, predisposing patients to severe hypoglycaemia.

Despite the increasing prevalence of PBH, clinical implications in this population are still unclear. Anecdotal evidence from patients with PBH suggests a high burden for these patients due to the recurrent hypoglycaemias with possibly debilitating consequences. It is well established that even mild hypoglycaemia (plasma glucose of 3.4 mmol/L) in diabetic and non-diabetic patients impairs various cognitive domains. Of note, some of the cognitive functions remain impaired for up to 75 min, even when the hypoglycaemia is corrected. Further concerns exist from observational studies showing associations between PBH during pregnancy and poor foetal growth.

Thus, it is important to timely detect and treat hypoglycaemia with an intervention that allows quick recovery of glycaemia to a safe level, thereby alleviating symptoms and eliminating the risk of potentially hazardous sequelae. Current diabetes-inspired guidelines recommend to correct hypoglycaemia with 15-20 g fast-acting carbohydrates, preferably glucose. However, clinical experience with PBH patients shows that the rapid spikes in glycaemia following correction of hypoglycaemia with such proposed strategies may trigger rebound hypoglycaemia in PBH patients. However, hypoglycaemia correction strategies that are tailored to the specific needs of PBH do not exist currently. Previous research suggests that glucose co-ingested with amino acids induces a metabolic environment that could be favourable for PBH patients due to elevated glucagon levels. However, it currently remains speculative whether combinations of amino acids with glucose could offer more suitable and sustainable PBH correction strategies.

Given the potentially hazardous consequences of hypoglycaemia, development of hypoglycaemia management strategies to adequately predict and treat critical blood glucose levels in the PBH population are urgently needed. Such strategies have to significantly lower the burden of PBH and increase patient safety.

The overall aim or the PBH forecast project (containing 3 WPs) is to prevent hypoglycaemic events in patients with PBH and to develop a sustainable hypoglycaemia correction strategy. The primary objective of WP 2 is to test different nutritional strategies for sustainable hypoglycaemia correction (e.g. minimising time spent hypoglycaemic without causing rebound hyper- and hypoglycaemia).

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • BE
    • Bern, BE, Switzerland, 3010
      • Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism (UDEM), Inselspital, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Post-bariatric surgery patients (Roux-en-Y gastric bypass) with PBH, defined as postprandial plasma or sensor glucose <3.0 mmol/L according to the International Hypoglycaemia Study Group and exclusion of other causes of hypoglycaemia
• Age ≥18 years

Exclusion Criteria:

• Inability to give informed consent as documented by signature
• Pregnant or lactating women
• Inability or contraindications to undergo the investigated intervention
• Drugs interfering with blood glucose (e.g. SGLT-2 inhibitors, acarbose) during the time of investigation
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment sequence 1; Sequence of the treatments: Glucose (15g) - Glucose (5g) -Protein bar	Other: 15 g dextrose; 15 g dextrose tablets; Other: 5 g dextrose; 5 g dextrose tablets; Other: Protein bar; 5 g carbohydrates + 10 g protein
Other: Treatment sequence 2; Sequence of the treatments: Glucose (15g) - Protein bar - Glucose (5g)	Other: 15 g dextrose; 15 g dextrose tablets; Other: 5 g dextrose; 5 g dextrose tablets; Other: Protein bar; 5 g carbohydrates + 10 g protein
Other: Treatment sequence 3; Sequence of the treatments: Glucose (5g) - Glucose (15g) - Protein bar	Other: 15 g dextrose; 15 g dextrose tablets; Other: 5 g dextrose; 5 g dextrose tablets; Other: Protein bar; 5 g carbohydrates + 10 g protein
Other: Treatment sequence 4; Sequence of the treatments: Glucose (5g) - Protein bar - Glucose (15g)	Other: 15 g dextrose; 15 g dextrose tablets; Other: 5 g dextrose; 5 g dextrose tablets; Other: Protein bar; 5 g carbohydrates + 10 g protein
Other: Treatment sequence 5; Sequence of the treatments: Protein bar - Glucose (15g) - Glucose (5g)	Other: 15 g dextrose; 15 g dextrose tablets; Other: 5 g dextrose; 5 g dextrose tablets; Other: Protein bar; 5 g carbohydrates + 10 g protein
Other: Treatment sequence 6; Sequence of the treatments: Protein bar - Glucose (5g) - Glucose (15g)	Other: 15 g dextrose; 15 g dextrose tablets; Other: 5 g dextrose; 5 g dextrose tablets; Other: Protein bar; 5 g carbohydrates + 10 g protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in glucose target range	The primary endpoint is time in glucose target range (plasma glucose 3.9-5.5 mmol/L).	During 40 minutes after hypoglycaemia correction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time with plasma glucose <3.0 mmol/L	Units: %	During 40 minutes after hypoglycaemia correction
Percentage of time with plasma glucose <3.9 mmol/L	Units: %	During 40 minutes after hypoglycaemia correction
Percentage of time with sensor glucose <3.0 mmol/L	The sensor glucose values will be adjusted to plasma glucose to increase accuracy	During 150 minutes after hypoglycaemia correction
Percentage of time with sensor glucose <3.9 mmol/L	The sensor glucose values will be adjusted to plasma glucose to increase accuracy	During 150 minutes after hypoglycaemia correction
Peak plasma glucose	Peak plasma glucose (mmol/L)	Until 40 minutes after inital hypoglycaemia correction or 180 minutes after meal intake (the later timepoint of the two)
Time to euglycaemia	Time to euglycaemia after hypoglycaemia correction (plasma glucose ≥3.9 mmol/L)	Until 40 minutes after inital hypoglycaemia correction or 180 minutes after meal intake (the later timepoint of the two)
Rebound hypoglycaemia	Proportion of participants with rebound hypoglycaemia (plasma glucose <3.0 mmol/L following successful primary hypoglycaemia correction defined as plasma glucose ≥3.9 mmol/L)	During 150 minutes after hypoglycaemia correction
Insulin	Serum insulin concentration	15 minutes after hypoglycaemia correction
Glucagon	Serum glucagon concentration	15 minutes after hypoglycaemia correction
Percentage of time with plasma glucose >5.5 mmol/L	Units: %	During 40 minutes after hypoglycaemia correction
Percentage of time with plasma glucose >10.0 mmol/L	Units: %	During 40 minutes after hypoglycaemia correction
Percentage of time with sensor glucose >5.5 mmol/L	The sensor glucose values will be adjusted to plasma glucose to increase accuracy	During 150 minutes after hypoglycaemia correction
Percentage of time with sensor glucose >10.0 mmol/L	The sensor glucose values will be adjusted to plasma glucose to increase accuracy	During 150 minutes after hypoglycaemia correction

Collaborators and Investigators

• Sponsor: Lia Bally
• Collaborators: University of Padova

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Actual): July 26, 2022
• Study Completion (Actual): July 26, 2022

Study Registration Dates

• First Submitted: January 14, 2022
• First Submitted That Met QC Criteria: February 10, 2022
• First Posted (Actual): February 22, 2022

Study Record Updates

• Last Update Posted (Estimate): December 7, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Continuous Glucose Monitoring
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia
• Other Study ID Numbers: PBH Forecast (WP 2)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All IPD that underlie results in a publication will be available to other researchers.
• IPD Sharing Time Frame: After study completion, 10 years
• IPD Sharing Access Criteria: Data will be shared after written inquiry and approval by the principal investigator.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

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