End-stage Renal Disease (ESRD), Gastrectomy, Gastric Bypass Surgery, Glucose Metabolism Disorders, Inflammation, Postprandial Hypoglycemia
Conditions
Keywords
Postprandial Hypoglycemia, End-Stage Renal Disease, Anakinra, Gastric Bypass, IL-1 receptor antagonist, Inflammation
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.
Interventions
DRUGAnakinra (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 the dialysis session.
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.
Sponsors
Marc Donath
Kantonsspital Baden
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
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.
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
This is an N-of-1 Trial, tailored-designed to a single participant. * total gastrectomy * severe episodes of postprandial hypoglycaemia after total gastrectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Amplitude of Sensor Glucose Excursions (MAGE) during Anakinra treatment compared to placebo | Through the 40-day interventional period | 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). |
| Prevalence and severity of postprandial hypoglycaemia symptoms during Anakinra treatment compared to placebo | Through the 40-day interventional period | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Below Range (TBR) | Through the 40-day interventional period | 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). |
| Time in hyperglycaemia | Through the 40-day interventional period | 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). |
| Pattern of Sensor Glucose | Through the 40-day interventional period | 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. |
| Comparison of Glycemic Variability and Extremes Between Interventional and Screening Period | From screening at Day -14 through the 40-day interventional 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. |
| Effect of Anakinra vs. Placebo on Glycemic and Hormonal Responses During Mixed Meal Tolerance Test | Immediately after 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: * Glucose * Insulin * c-peptide * GLP-1 * Glucagon * Cortisol |
| Changes in Fasting Metabolic and Inflammatory Biomarkers After the Interventional Period Compared to Baseline | Through the 40-day interventional period | 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. |
| Comparison of Prevalence and Severity of Postprandial Hypoglycemia Symptoms Between the Interventional and Screening Periods | From screening at Day -14 through the 40-day interventional period | 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). |
| Subjective patient's daily preference for treatment period | Through the 40-day interventional 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. |
| Adverse events of interest | From first dose of anakinra (Visit 4, Day 3) through the 40-day interventional Period and 15-day follow-up period | Adverse events of interest: AEs of interest include adverse events that can be expected during a treatment with Anakinra. * Identification of hypersensitivity reaction during the Interventional period. * Detection of any infection during the interventional period. * Detection of Neutropenia during the interventional period, defined as absolute neutrophil count \<1000/mm³. * Detection of Thrombocytopenia during the Interventional period, defined as platelet count \<100 000/mm³. |
| Serious Adverse Events | From screening on Day -14 through the 40-day interventional period and 15-day follow-up period | 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. |
Countries
Switzerland
Contacts
CONTACTMarc Donath, Prof. Dr. Med
PRINCIPAL_INVESTIGATORMatthias Hepprich, PD Dr. med.
University of Basel, Claraspital Basel
Outcome results
None listed