Clinical trial NCT05174507: Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes
Official title: Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes: a Randomized, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Postprandial Hypoglycemia
Keywords: SGLT2-inhibitor empagliflozin
IL-1 receptor antagonist anakinra
prediabetes
insulin clearance
proinsulin
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2021-12-30
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Placebo controlled, double-blind, randomized, cross-over proof-of-concept study. Subjects will be randomized to either group 1-6 (ratio 1:1, in blocks of 4 participants).
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of symptomatic hypoglycemia
timeFrame: up to 3 hours after ingestion of the liquid mixed-meal
Secondary outcomes:
measure: Severity of symptoms of hypoglycemia according to the Edinburgh Hypoglycemia Scale
timeFrame: up to 3 hours after ingestion of the liquid mixed-meal
measure: Nadir plasma glucose (mmol/l)
timeFrame: up to 3 hours after ingestion of the liquid mixed-meal
measure: Change in proinsulin to insulin ratio in serum
timeFrame: at baseline and 60 min after ingestion of the mixed meal
measure: Change in inflammatory state
timeFrame: at baseline and 60 min after ingestion of the mixed meal
measure: Change in RNA sequencing (RNAseq) in peripheral PBMC
timeFrame: at baseline and 60 min after ingestion of the mixed meal
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel
Study officials:
affiliation: Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel
name: Marc Y. Donath, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: