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| Name | Class |
|---|---|
| Kantonsspital Baden | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Time Below Range (TBR) | Time Below Range (TBR): The percentage and total duration of sensor glucose readings below thresholds of 3.3 mmol/L, 3.0 mmol/L, and 2.7 mmol/L during Anakinra treatment compared to placebo, assessed using cumulative data from all 48-hour treatment periods (48 hours following study-drug administration, Anakinra or Placebo). | Through the 40-day interventional period |
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This is an N-of-1 Trial, tailored-designed to a single participant.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marc Donath, Prof. Dr. Med | Contact | +41 56 486 25 52 | marc.donath@umontreal.ca |
| Name | Affiliation | Role |
|---|---|---|
| Matthias Hepprich, PD Dr. med. | University of Basel, Claraspital Basel | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kantonsspital Olten | Olten | Canton of Solothurn | 4600 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26892512 | Background | 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. | |
| 27336358 | Background |
| Label | URL |
|---|---|
| Related Info | View source |
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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.
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| 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. |
|
| Time in hyperglycaemia | Time in hyperglycaemia: The percentage and total duration of sensor glucose readings above 10 mmol/L during Anakinra treatment compared to Placebo, assessed using cumulative data from all 48-hour treatment periods (48 hours following study-drug administration, Anakinra or Placebo). | Through the 40-day interventional period |
| Pattern of Sensor Glucose | Pattern of Sensor Glucose: The slope of postprandial glucose measurements calculated as the maximal rate of increase and decrease of glucose levels observed over 20 minutes in the postprandial period, compared between Anakinra treatment and placebo, based on data from all 48-hour treatment periods (48 hours following study-drug administration, Anakinra or Placebo). The postprandial period is defined as the 3 hours following meal intake. | Through the 40-day interventional period |
| Comparison of Glycemic Variability and Extremes Between Interventional and Screening Period | Comparison of the entire interventional period with the screening period regarding to the following parameters as defined above: Time Below Range, Time in hyperglycaemia, Pattern of Sensor Glucose, and Mean Amplitude of Glucose Excursions. | 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 | Changes following treatment with Anakinra compared to placebo during a Mixed Meal Tolerance Test in the AUC, peak and nadir values, and slopes of:
| Immediately after Mixed-meal tolerance test |
| Changes in Fasting Metabolic and Inflammatory Biomarkers After the Interventional Period Compared to Baseline | Changes following the entire interventional period in levels of fasting insulin, c-peptide, glucagon, HbA1c, IL-1Ra, IL-6, TNF-a, IL-18 and hsCRP as compared to Baseline. | Through the 40-day interventional period |
| Comparison of Prevalence and Severity of Postprandial Hypoglycemia Symptoms Between the Interventional and Screening Periods | Prevalence and severity of postprandial hypoglycaemia symptoms during the whole interventional period compared to the Screening period. 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). | From screening at Day -14 through the 40-day interventional period |
| Subjective patient's daily preference for treatment period | The patient will be asked to provide feedback on the treatment periods, indicating which study days he found the treatment more tolerable or beneficial. This subjective assessment will take into account factors such as comfort, side effects, and overall experience during the interventional period. | Through the 40-day interventional period |
| Adverse events of interest | Adverse events of interest: AEs of interest include adverse events that can be expected during a treatment with Anakinra.
| From first dose of anakinra (Visit 4, Day 3) through the 40-day interventional Period and 15-day follow-up period |
| Serious Adverse Events | A Serious Adverse Event (SAE) is classified as any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. | From screening on Day -14 through the 40-day interventional period and 15-day follow-up period |
| 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. |
| 24468184 | 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. |
| 27865808 | 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. |
| 24315990 | 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. |
| 24902654 | 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. |
| 22398113 | 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. |
| 25737101 | 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. |
| 12844139 | 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. |
| 35863559 | 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. |
| 9987089 | 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. |
| 14871424 | 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. |
| 32197070 | 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. |
| 28092375 | 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. |
| 17895322 | 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. |
| 30101281 | 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. |
| 20495972 | 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. |
| 25866150 | 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. |
| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| D007676 | Kidney Failure, Chronic |
| D044882 | Glucose Metabolism Disorders |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D053590 | Interleukin 1 Receptor Antagonist Protein |
| D019947 | Receptors, Interleukin-6 |
| ID | Term |
|---|---|
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D018123 | Receptors, Interleukin |
| D018121 | Receptors, Cytokine |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
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