Controlled Insulin Delivery: Combining Technology With Treatment
18 mars 2021 uppdaterad av: Sansum Diabetes Research Institute
Hypothesis: Closed-loop control systems for an artificial pancreas using multi-parametric model predictive control can be developed and evaluated safely in patients with Type 1 Diabetes Mellitus (T1DM) to control blood glucose concentrations.
This study seeks to combine real-time continuous glucose sensing with automated insulin delivery in a closed-loop system that will achieve euglycemia in patients with T1DM. The end result of this line of research will be an artificial pancreas that will provide around-the-clock glucose regulation through controlled insulin delivery in response to detected patterns of change in glucose levels.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
The goal of the JDRF Artificial Pancreas Project is to produce an autonomous artificial pancreas that can safely and effectively regulate glycemia in people with type 1 diabetes mellitus.
In our work, this fully automated closed-loop system combines a subcutaneous continuous glucose monitor (CGM) and a continuous subcutaneous insulin infusion (CSII) pump with a sophisticated control algorithm.
This is a proof-of-concept study to demonstrate that the controller could bring the patient back to a relatively normal glucose concentration after an unannounced meal and from mild hyperglycemia.
Once the system is initiated, all insulin delivery is calculated automatically.
There was no outside intervention either by the subject or medical personnel.
An artificial pancreas system that aims at replicating normal beta-cell function by using the subcutaneous-subcutaneous (sc-sc) route needs to address inherent delays in both glucose sensing and insulin delivery.
Our strategic approach is that a closed-loop system should operate safely without any knowledge of meals or other disturbances.
We have developed the Artificial Pancreas System (APS©) and used it to clinically evaluate a control strategy that allows efficient glycemic control without any a priori meal information.
The Artificial Pancreas device uses the Artificial Pancreas System (APS©) platform with the OmniPod insulin pump, the DexCom SEVEN PLUS CGM and a multi-parametric model predictive control algorithm (mpMPC) with an insulin-on-board (IOB) safety constraint.
Studietyp
Interventionell
Inskrivning (Faktisk)
19
Fas
- Tidig fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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California
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Santa Barbara, California, Förenta staterna, 93105
- Sansum Diabetes Research Institute
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Petah Tikva, Israel
- Schneider Children's Medical Center of Israel
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Willing to sign the consent form
- Type 1 diabetes for at least 1 year prior to the study
- Using continuous subcutaneous insulin infusion pump
- Above 21 years of age
- Willing to follow the study requirements
Exclusion Criteria:
- Allergy to the sensor or to one of its components
- Psychiatric disorders
- Reported diabetic ketoacidosis within last 3 months
- Abnormal liver function (Transaminase > 2 times the upper limit of normal)
- Heart failure
- Any carcinogenic disease
- Any other chronic abnormality
- Unwilling to perform or to follow the research protocol
- Participation in any other study concurrent with the proposed study
- Creatinine concentration above the upper limit of normal for age and sex
- Active coronary artery disease
- Active gastroparesis
- History of uncontrolled seizures
- Pregnancy
- Untreated adrenal insufficiency
- Hypokalemia
- Uncontrolled thyroid disease.
- Condition, which in the opinion of the investigator, would interfere with patient safety
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Closed-loop control system
The objective of this study is to automate glucose control in subjects with type 1 diabetes using a computer control algorithm in a controlled in-clinic research setting. The controller will be evaluated under two conditions:
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Subjects will arrive fasting at 7am unless needed for hypoglycemia (glucose < 70 mg/dL) and no extra bolus insulin after 3am. An IV catheter will be inserted for blood samples and for IV administration of glucose if necessary. Blood samples will be analyzed for glucose by YSI 2300Stat every 30 minutes. Breakfast consisting of 25g of CHO will be eaten at 7:30 am and the subject will bolus for this amount of CHO. The controller is switched "on" on the down slope of the meal response, and the subject is brought to a basal steady-state by the controller. Target blood glucose is 110 ± 30-mg/dL. After approximately 3 hours a small lunch will be eaten consisting of 25g of CHO (unannounced meal challenge). The subject will be monitored until blood glucose returns to euglycemia.
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Restoration of Euglycemia
Tidsram: 12 hours
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The primary endpoint of this pilot study is successful restoration of euglycemia from the two perturbed conditions using closed loop control with minimal hypo- and hyperglycemia exposure.
The first condition involves restoration of euglycemia when the subject is in a hyperglycemic state.
The second condition involves restoration of euglycemia following consumption of a meal containing 25g CHO with no insulin bolus.
The patients will be followed for the duration of the 12 hour study.
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12 hours
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Average percent-of-time-in-range (80 - 180 mg/dL)
Tidsram: 12 hours
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All reported blood glucose values per both CGM and YSI ware analyzed for average percent-of-time-in-range (80 - 180 mg/dL).
The participants will be followed for the duration of the 12 hour study.
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12 hours
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Utredare
- Huvudutredare: Lois Jovanovic, M.D., Sansum Diabetes Research Institute
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
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- Steil GM, Panteleon AE, Rebrin K. Closed-loop insulin delivery-the path to physiological glucose control. Adv Drug Deliv Rev. 2004 Feb 10;56(2):125-44. doi: 10.1016/j.addr.2003.08.011.
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- Dassau E, Palerm CC, Zisser H, Buckingham BA, Jovanovic L, Doyle FJ. In silico evaluation platform for artificial pancreatic beta-cell development--a dynamic simulator for closed-loop control with hardware-in-the-loop. Diabetes Technol Ther. 2009 Mar;11(3):187-94. doi: 10.1089/dia.2008.0055.
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- Diabetes Research in Children Network (DirecNet) Study Group; Buckingham B, Beck RW, Tamborlane WV, Xing D, Kollman C, Fiallo-Scharer R, Mauras N, Ruedy KJ, Tansey M, Weinzimer SA, Wysocki T. Continuous glucose monitoring in children with type 1 diabetes. J Pediatr. 2007 Oct;151(4):388-93, 393.e1-2. doi: 10.1016/j.jpeds.2007.03.047. Epub 2007 Aug 24.
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- Garg S, Zisser H, Schwartz S, Bailey T, Kaplan R, Ellis S, Jovanovic L. Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor: a randomized controlled trial. Diabetes Care. 2006 Jan;29(1):44-50. doi: 10.2337/diacare.29.01.06.dc05-1686.
- Hovorka R, Chassin LJ, Wilinska ME, Canonico V, Akwi JA, Federici MO, Massi-Benedetti M, Hutzli I, Zaugg C, Kaufmann H, Both M, Vering T, Schaller HC, Schaupp L, Bodenlenz M, Pieber TR. Closing the loop: the adicol experience. Diabetes Technol Ther. 2004 Jun;6(3):307-18. doi: 10.1089/152091504774197990.
- Hovorka R, Shojaee-Moradie F, Carroll PV, Chassin LJ, Gowrie IJ, Jackson NC, Tudor RS, Umpleby AM, Jones RH. Partitioning glucose distribution/transport, disposal, and endogenous production during IVGTT. Am J Physiol Endocrinol Metab. 2002 May;282(5):E992-1007. doi: 10.1152/ajpendo.00304.2001.
- Jeha GS, Karaviti LP, Anderson B, Smith EO, Donaldson S, McGirk TS, Haymond MW. Insulin pump therapy in preschool children with type 1 diabetes mellitus improves glycemic control and decreases glucose excursions and the risk of hypoglycemia. Diabetes Technol Ther. 2005 Dec;7(6):876-84. doi: 10.1089/dia.2005.7.876.
- Jones SM, Quarry JL, Caldwell-McMillan M, Mauger DT, Gabbay RA. Optimal insulin pump dosing and postprandial glycemia following a pizza meal using the continuous glucose monitoring system. Diabetes Technol Ther. 2005 Apr;7(2):233-40. doi: 10.1089/dia.2005.7.233.
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- Klonoff DC. A review of continuous glucose monitoring technology. Diabetes Technol Ther. 2005 Oct;7(5):770-5. doi: 10.1089/dia.2005.7.770. No abstract available.
- Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke W. Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care. 1998 Nov;21(11):1870-5. doi: 10.2337/diacare.21.11.1870.
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- Lehmann ED, Deutsch T. Compartmental models for glycaemic prediction and decision-support in clinical diabetes care: promise and reality. Comput Methods Programs Biomed. 1998 May;56(2):193-204. doi: 10.1016/s0169-2607(98)00025-x.
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- Magni L, Raimondo DM, Man CD, Breton M, Patek S, Nicolao GD, Cobelli C, Kovatchev BP. Evaluating the efficacy of closed-loop glucose regulation via control-variability grid analysis. J Diabetes Sci Technol. 2008 Jul;2(4):630-5. doi: 10.1177/193229680800200414.
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Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 juli 2008
Primärt slutförande (Faktisk)
1 januari 2010
Avslutad studie (Faktisk)
1 januari 2010
Studieregistreringsdatum
Först inskickad
15 november 2011
Först inskickad som uppfyllde QC-kriterierna
30 november 2011
Första postat (Uppskatta)
2 december 2011
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
23 mars 2021
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
18 mars 2021
Senast verifierad
1 mars 2021
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- JDRF 22-2009-796
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