Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes

Postprandial Hypoglycemia Clinical Trial

— Hypo-PrEA  

Official title:

Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes: a Randomized, Placebo-controlled Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05174507
• Other study ID #: 2020-01287; me20Donath
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 24, 2022
• Est. completion date: May 2024

Study information

• Verified date: February 2024
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to analyze whether the SGLT2-inhibitor empagliflozin or the IL-1 receptor antagonist anakinra may improve postprandial hypoglycemia in subjects with prediabetes.

Description:

Subjects with prediabetes may develop postprandial hypoglycemia. This is probably due to a dysfunction of the insulin producing β-cell characterized by a delayed and exaggerated insulin secretion leading to an initial peak in glycaemia followed by a rapid fall and eventually resulting in hypoglycemia. The latter occurring typically within 1 to 3 hours after food intake.

In patients with gastric bypass surgery and postprandial hypoglycemia the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra reduced postprandial insulin release and prevented hypoglycemia. This study is to analyze whether a similar therapeutic approach using empagliflozin and anakinra may also improve postprandial hypoglycemia in subjects with prediabetes.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 26
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects with prediabetes defined by Glycosylated haemoglobin A1c (HbA1c) 5.7-6.4 % or fasting plasma glucose 6.1-6.9 mmol/l) or plasma glucose 2 h following 75 glucose ingestion of 7.8-11.0 mmol/l.

• Hypoglycemia occuring 1 to 3 h following ingestion of a standardized liquid mixed-meal (75 g carbohydrates) and fulfilling the Whipple's triad (glucose below 3.0 mmol/l).

• Age = 18 years

• For subjects with reproductive potential, willingness to use contraceptive measures adequate to prevent the subject from becoming pregnant during the study

Exclusion Criteria:

• Upper gastrointestinal surgery

• Diagnosis of any type of diabetes mellitus

• Signs of current infection

• Use of investigational drug up to one week prior to start of treatment phase

• Glucocorticoid therapy

• Neutropenia (leukocyte count < 1.5 × 109/L or absolute neutrophil count (ANC) < 0.5 × 109/L)

• Anemia (hemoglobin < 11 g/dL for males, < 10 g/dL for females)

• Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, aspartate aminotransferase (AST)/ALT > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN)

• Uncontrolled disease

• Currently pregnant or breastfeeding

• No subjects meeting the criteria for vulnerability

• Participation in another study with investigational drug within the 30 days preceding and during the present study.

Related Conditions & MeSH terms

• Glucose Intolerance
• Hypoglycemia
• Postprandial Hypoglycemia
• Prediabetic State

Intervention

Drug:
• empagliflozin
Empagliflozin (Jardiance®; Boehringer Ingelheim (Schweiz) GmbH) is a highly selective, reversible inhibitor of the sodium glucose co-transporter 2 (SGLT2). Treatment consists of a single oral tablet of 25 mg of empagliflozin (Jardiance®) two hours before ingestion of the mixed-meal (Ensure plus® 375 ml, 75 g carbohydrates, 562 kcal, drinking time 5 minutes).
• anakinra
Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB) is a recombinant, non-glycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra) in a 100 mg/0.67ml solution for SC injection. Treatment consists of a single subcutaneous injection of 100 mg Anakinra (Kineret®) three hours before ingestion of the mixed-meal (Ensure plus® 375 ml, 75 g carbohydrates, 562 kcal, drinking time 5 minutes).

Other:
• saline subcutaneous (s.c.) (placebo)
Placebo for anakinra is 0.67 ml of sterile 0.9 % saline solution s. c. Treatment consists of a single subcutaneous injection of matched placebo (0.67 ml of 0.9 % saline) three hours before ingestion of the mixed-meal (Ensure plus® 375 ml, 75 g carbohydrates, 562 kcal, drinking time 5 minutes).
• tablet per oral (p.o.) (placebo)
Placebo for empagliflozin is Winthrop P® (Zentiva, Frankfurt/Main) lactose tablet. Treatment consists of a single oral tablet of matched placebo two hours before ingestion of the mixed-meal (Ensure plus® 375 ml, 75 g carbohydrates, 562 kcal, drinking time 5 minutes).

Locations

Country	Name	City	State
Switzerland	Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of symptomatic hypoglycemia	Incidence of symptomatic hypoglycemia following a standardized mixed-meal test defined by appearance of typical symptoms, blood glucose level below 3.0 mmol/l and relief of symptoms when the glucose level is raised (Whipple's triad).	up to 3 hours after ingestion of the liquid mixed-meal
Secondary	Severity of symptoms of hypoglycemia according to the Edinburgh Hypoglycemia Scale	The Edinburgh Hypoglycemia Scale is a classification of the 11 most common symptoms of hypoglycemia. Subjective intensity-grading: no symptoms 0; light symptoms 1; moderate symptoms 2; severe symptoms 3	up to 3 hours after ingestion of the liquid mixed-meal
Secondary	Nadir plasma glucose (mmol/l)	Nadir plasma glucose (mmol/l)	up to 3 hours after ingestion of the liquid mixed-meal
Secondary	Change in proinsulin to insulin ratio in serum	Change in proinsulin to insulin ratio in serum	at baseline and 60 min after ingestion of the mixed meal
Secondary	Change in inflammatory state	Change in inflammatory laboratory parameters (Interleukin (IL)1ß, IL6, Tumor necrosis factor (TNF) a, IL-10, IL-1Ra) in supernatants of Lipopolysaccharide (LPS)-stimulated and unstimulated peripheral blood mononuclear cells (PBMC)	at baseline and 60 min after ingestion of the mixed meal
Secondary	Change in RNA sequencing (RNAseq) in peripheral PBMC	Change in RNAseq in peripheral PBMC	at baseline and 60 min after ingestion of the mixed meal