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

NCT07580079 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-00684
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postprandial Hypoglycemia; End-stage Renal Disease (ESRD); Gastrectomy; Glucose Metabolism Disorders; Inflammation; Gastric Bypass Surgery

Keywords

Postprandial Hypoglycemia; End-Stage Renal Disease; Anakinra; Gastric Bypass; IL-1 receptor antagonist; Inflammation

Outcome Measures

Primary Outcomes (2)

• Mean Amplitude of Sensor Glucose Excursions (MAGE) during Anakinra treatment compared to placebo

  Mean Amplitude of Sensor Glucose Excursions (MAGE) during Anakinra treatment compared to placebo, assessed using cumulative data from Continuous Glucose Monitoring System from all 48-hour treatment periods (48 hours following study-drug administration, Anakinra or Placebo).

  Through the 40-day interventional period

• Prevalence and severity of postprandial hypoglycaemia symptoms during Anakinra treatment compared to placebo

  Prevalence and severity of postprandial hypoglycaemia symptoms during Anakinra treatment compared to placebo, assessed using cumulative data from Continuous Glucose Monitoring from all 48-hour treatment periods. Post-prandial hypoglycaemia symptoms and their severity will be evaluated by the patient using the Edinburgh Hypoglycemia Symptom Scale (EHSS) and are accompanied by a decrease in blood glucose levels within the postprandial period as evaluated through the CGMS. The postprandial period is defined as the 3 hours following meal intake. A minimum blood glucose cut-off value is not required for symptom reporting. Each treatment period spans the 48 hours following study-drug administration (Anakinra or Placebo).

  Through the 40-day interventional period

Secondary Outcomes (10)

• Time Below Range (TBR)

  Through the 40-day interventional period

• Time in hyperglycaemia

  Through the 40-day interventional period

• Pattern of Sensor Glucose

  Through the 40-day interventional period

• Comparison of Glycemic Variability and Extremes Between Interventional and Screening Period

  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

  Immediately after Mixed-meal tolerance test

Study Arms (2)

Placebo Treatment Periods

PLACEBO COMPARATOR

The interventional period consists of four treatment blocks, each containing four visits. During each visit, the patient receives either Anakinra (A) or placebo (P) in a double-blinded manner, according to a randomized schedule. The sequence within each block (e.g., A-A-P-P or P-A-A-P) is randomly assigned in advance by an independent scientist, ensuring a balanced and unbiased comparison of treatments throughout the trial. Study visits take place during the patient's regular dialysis sessions. On each visit, the assigned treatment is administered via the hemodialysis blood circuit over 1 minute during the last 30 minutes of each dialysis session by the dialysis personnel.

Drug: Placebo Comparator (0.9% NaCl)

Anakinra Treatment Periods

EXPERIMENTAL

The interventional period consists of four treatment blocks, each containing four visits. During each visit, the patient receives either Anakinra (A) or placebo (P) in a double-blinded manner, according to a randomized schedule. The sequence within each block (e.g., A-A-P-P or P-A-A-P) is randomly assigned in advance by an independent scientist, ensuring a balanced and unbiased comparison of treatments throughout the trial. Study visits take place during the patient's regular dialysis sessions. On each visit, the assigned treatment is administered via the hemodialysis blood circuit over 1 minute during the last 30 minutes of each dialysis session by the dialysis personnel.

Drug: Anakinra (interleukin-1 receptor antagonist)

Interventions

Anakinra (interleukin-1 receptor antagonist) DRUG

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 the dialysis session.

Anakinra Treatment Periods

Placebo Comparator (0.9% NaCl) DRUG

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.

Placebo Treatment Periods

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

This is an N-of-1 Trial, tailored-designed to a single participant. * total gastrectomy * severe episodes of postprandial hypoglycaemia after total gastrectomy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Marc Donath: lead
• Kantonsspital Baden: collaborator

Study Sites (1)

Kantonsspital Olten

Olten, Canton of Solothurn, 4600, Switzerland

Location

Related Publications (18)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Yang BB, Baughman S, Sullivan JT. Pharmacokinetics of anakinra in subjects with different levels of renal function. Clin Pharmacol Ther. 2003 Jul;74(1):85-94. doi: 10.1016/S0009-9236(03)00094-8.

  PMID: 12844139 BACKGROUND

• Dember LM, Hung A, Mehrotra R, Hsu JY, Raj DS, Charytan DM, Mc Causland FR, Regunathan-Shenk R, Landis JR, Kimmel PL, Kliger AS, Himmelfarb J, Ikizler TA; Hemodialysis Novel Therapies Consortium. A randomized controlled pilot trial of anakinra for hemodialysis inflammation. Kidney Int. 2022 Nov;102(5):1178-1187. doi: 10.1016/j.kint.2022.06.022. Epub 2022 Jul 19.

  PMID: 35863559 BACKGROUND

• Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 1999 Feb;55(2):648-58. doi: 10.1046/j.1523-1755.1999.00273.x.

  PMID: 9987089 BACKGROUND

• Eustace JA, Astor B, Muntner PM, Ikizler TA, Coresh J. Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease. Kidney Int. 2004 Mar;65(3):1031-40. doi: 10.1111/j.1523-1755.2004.00481.x.

  PMID: 14871424 BACKGROUND

• Hepprich M, Wiedemann SJ, Schelker BL, Trinh B, Starkle A, Geigges M, Loliger J, Boni-Schnetzler M, Rudofsky G, Donath MY. Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1beta. Cell Metab. 2020 Apr 7;31(4):699-709.e5. doi: 10.1016/j.cmet.2020.02.013. Epub 2020 Mar 19.

  PMID: 32197070 BACKGROUND

• Dror E, Dalmas E, Meier DT, Wueest S, Thevenet J, Thienel C, Timper K, Nordmann TM, Traub S, Schulze F, Item F, Vallois D, Pattou F, Kerr-Conte J, Lavallard V, Berney T, Thorens B, Konrad D, Boni-Schnetzler M, Donath MY. Postprandial macrophage-derived IL-1beta stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat Immunol. 2017 Mar;18(3):283-292. doi: 10.1038/ni.3659. Epub 2017 Jan 16.

  PMID: 28092375 BACKGROUND

• Goldfine AB, Mun EC, Devine E, Bernier R, Baz-Hecht M, Jones DB, Schneider BE, Holst JJ, Patti ME. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J Clin Endocrinol Metab. 2007 Dec;92(12):4678-85. doi: 10.1210/jc.2007-0918. Epub 2007 Sep 25.

  PMID: 17895322 BACKGROUND

• Salehi M, Vella A, McLaughlin T, Patti ME. Hypoglycemia After Gastric Bypass Surgery: Current Concepts and Controversies. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2815-2826. doi: 10.1210/jc.2018-00528.

  PMID: 30101281 BACKGROUND

• Marsk R, Jonas E, Rasmussen F, Naslund E. Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986-2006 in Sweden. Diabetologia. 2010 Nov;53(11):2307-11. doi: 10.1007/s00125-010-1798-5. Epub 2010 May 22.

  PMID: 20495972 BACKGROUND

• Lee CJ, Clark JM, Schweitzer M, Magnuson T, Steele K, Koerner O, Brown TT. Prevalence of and risk factors for hypoglycemic symptoms after gastric bypass and sleeve gastrectomy. Obesity (Silver Spring). 2015 May;23(5):1079-84. doi: 10.1002/oby.21042. Epub 2015 Apr 10.

  PMID: 25866150 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Hypoglycemia; Kidney Failure, Chronic; Glucose Metabolism Disorders; Inflammation

Interventions

Interleukin 1 Receptor Antagonist Protein; Receptors, Interleukin-6

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Receptors, Interleukin; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Matthias Hepprich, PD Dr. med.

  University of Basel, Claraspital Basel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc Donath, Prof. Dr. Med

CONTACT

+41 56 486 25 52; marc.donath@umontreal.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med Marc Y. Donath, Sponsor-Investigator

Model Details: The interventional period will consist of four treatment blocks, each containing four visits. During each visit, the patient will receive either Anakinra (A) or placebo (P) in a double-blinded manner, according to a randomized schedule. The sequence within each block (e.g., A-A-P-P or P-A-A-P) will be randomly assigned in advance by an independent scientist, ensuring a balanced and unbiased comparison of treatments throughout the trial. The visits are taking place parallel to the patient's scheduled dialysis treatment. On each visit, the assigned treatment will be administered via the hemodialysis blood circuit over 1 minute during the last 30 minutes of each dialysis session by the dialysis personnel.

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: May 12, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 12, 2026

Record last verified: 2026-04

Locations

CH (1)