Anakinra for the Treatment of Postprandial Hypoglycemia in a Patient With Total Gastrectomy and End-Stage Renal Disease

Official title

Anakinra for the Treatment of Recurrent Postprandial Hypoglycemia After Total Gastrectomy in a Patient With End-Stage Renal Disease

Overview

Post-meal low blood sugar (postprandial hypoglycemia) is a common problem after certain stomach surgeries like gastric bypass or stomach removal. It usually happens 1 to 3 hours after eating and can cause symptoms such as tiredness, hunger, sweating, dizziness, trouble speaking, or even fainting. Right now, there is no approved medication for this condition-only a careful diet reduced in sugars and refined carbohydrates can sometimes help reduce symptoms. The AnPHy-ReD study is a personalized research study, designed for just one patient. This patient is a 52-year-old man who has been struggling with severe post-meal low blood sugar ever since his stomach was removed due to tumor in 2017. He also has end-stage kidney disease and needs dialysis three times a week. The study is being conducted at the Cantonal Hospital of Olten in Switzerland and lasts 10 weeks, including 24 study visits. Most of these visits will happen during the patient's regular dialysis sessions. For 6 weeks, the patient will take either the drug Anakinra or a placebo (a substance with no active ingredient), in a randomly chosen order. Neither the patient nor the doctors will know which one he is taking at any given time. During the study, the medical team will perform various tests, including physical check-ups and blood samples to look at sugar levels, various hormone levels and inflammation in the body. The patient will also wear a continuous glucose monitor (CGM) to track his blood sugar levels 24/7. In addition, he will do several mixed meal tests-this means drinking a shake containing fats, proteins, and sugars during a study appointment to see in real time how his body processes food, with doctors measuring changes in blood sugar, hormone and inflammation markers over time. During the study duration any side effects or symptoms will be closely monitored. At the end of the study, the team will compare the results between the times the patient took Anakinra and the times he took the placebo. This will help find out if Anakinra can reduce sharp drops in blood sugar after meals and improve his overall condition.

Interventions

• Drug Anakinra (interleukin-1 receptor antagonist)
  Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB) is a recombinant, non-glycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra). It is a clear, colourless-to-white solution, provided as a 150mg/mL solution in pre-filled syringes, each containing of 100 mg of Anakinra in 0.67ml. On the assigned study days, the patient will receive in a double-blind manner 100 mg of Anakinra intravenously through the hemodialysis circuit, administered 30 minutes before the end of t
• Drug Placebo Comparator (0.9% NaCl)
  Placebo comparator will be 0.9% saline solution. A similar size and type of syringe will be used as for the Anakinra syringe making it difficult to distinguish which treatment of the two the patient is receiving. The patient will receive 0.9% saline solution intravenously through the haemodialysis circuit 30 minutes before the end of the dialysis session, following the same administration procedure as Anakinra to maintain blinding.

Primary outcome measures

• Mean Amplitude of Sensor Glucose Excursions (MAGE) during Anakinra treatment compared to placebo [Time frame: Through the 40-day interventional period]
• Prevalence and severity of postprandial hypoglycaemia symptoms during Anakinra treatment compared to placebo [Time frame: Through the 40-day interventional period]

Secondary outcome measures (10)

• Time Below Range (TBR) [Time frame: Through the 40-day interventional period]
• Time in hyperglycaemia [Time frame: Through the 40-day interventional period]
• Pattern of Sensor Glucose [Time frame: Through the 40-day interventional period]
• Comparison of Glycemic Variability and Extremes Between Interventional and Screening Period [Time frame: From screening at Day -14 through the 40-day interventional period]
• Effect of Anakinra vs. Placebo on Glycemic and Hormonal Responses During Mixed Meal Tolerance Test [Time frame: Immediately after Mixed-meal tolerance test]
• Changes in Fasting Metabolic and Inflammatory Biomarkers After the Interventional Period Compared to Baseline [Time frame: Through the 40-day interventional period]
• Comparison of Prevalence and Severity of Postprandial Hypoglycemia Symptoms Between the Interventional and Screening Periods [Time frame: From screening at Day -14 through the 40-day interventional period]
• Subjective patient's daily preference for treatment period [Time frame: Through the 40-day interventional period]
• Adverse events of interest [Time frame: From first dose of anakinra (Visit 4, Day 3) through the 40-day interventional Period and 15-day follow-up period]
• Serious Adverse Events [Time frame: From screening on Day -14 through the 40-day interventional period and 15-day follow-up period]

Eligibility criteria

This is an N-of-1 Trial, tailored-designed to a single participant.

• total gastrectomy
• severe episodes of postprandial hypoglycaemia after total gastrectomy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Treatment

Study locations

Switzerland · 1 center

• Kantonsspital Olten — Olten

Publications

• Vaurs C, Brun JF, Bertrand M, Burcelin R, du Rieu MC, Anduze Y, Hanaire H, Ritz P. Post-prandial hypoglycemia results from a non-glucose-dependent inappropriate insulin secretion in Roux-en-Y gastric bypassed patients. Metabolism. 2016 Mar;65(3):18-26. doi: 10.1016/j.metabol.2015.10.020. Epub 2015 Oct 23. PMID 26892512
• Nannipieri M, Belligoli A, Guarino D, Busetto L, Moriconi D, Fabris R, Mari A, Baldi S, Anselmino M, Foletto M, Vettor R, Ferrannini E. Risk Factors for Spontaneously Self-Reported Postprandial Hypoglycemia After Bariatric Surgery. J Clin Endocrinol Metab. 2016 Oct;101(10):3600-3607. doi: 10.1210/jc.2016-1143. Epub 2016 Jun 23. PMID 27336358
• Patti ME, Goldfine AB. Hypoglycemia after gastric bypass: the dark side of GLP-1. Gastroenterology. 2014 Mar;146(3):605-8. doi: 10.1053/j.gastro.2014.01.038. Epub 2014 Jan 24. No abstract available. PMID 24468184
• Ohrstrom CC, Worm D, Hansen DL. Postprandial hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass: an update. Surg Obes Relat Dis. 2017 Feb;13(2):345-351. doi: 10.1016/j.soard.2016.09.025. Epub 2016 Sep 28. PMID 27865808
• Salehi M, Gastaldelli A, D'Alessio DA. Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass. Gastroenterology. 2014 Mar;146(3):669-680.e2. doi: 10.1053/j.gastro.2013.11.044. Epub 2013 Dec 4. PMID 24315990
• Botros N, Rijnaarts I, Brandts H, Bleumink G, Janssen I, de Boer H. Effect of carbohydrate restriction in patients with hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass. Obes Surg. 2014 Nov;24(11):1850-5. doi: 10.1007/s11695-014-1319-6. PMID 24902654
• Roslin MS, Oren JH, Polan BN, Damani T, Brauner R, Shah PC. Abnormal glucose tolerance testing after gastric bypass. Surg Obes Relat Dis. 2013 Jan-Feb;9(1):26-31. doi: 10.1016/j.soard.2011.11.023. Epub 2012 Jan 27. PMID 22398113
• Kefurt R, Langer FB, Schindler K, Shakeri-Leidenmuhler S, Ludvik B, Prager G. Hypoglycemia after Roux-En-Y gastric bypass: detection rates of continuous glucose monitoring (CGM) versus mixed meal test. Surg Obes Relat Dis. 2015 May-Jun;11(3):564-9. doi: 10.1016/j.soard.2014.11.003. Epub 2014 Nov 13. PMID 25737101

Identifiers

NCT: NCT07580079 · 2025-00684

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗