Diabetes
Conditions
Keywords
Diabetes, Diabetes Mellitus, Type 1 diabetes, Insulin Pump users, Intradermal insulin
Brief summary
The primary objective of this study is to investigate if intradermal (in the skin) basal and bolus insulin delivery of a fast acting insulin analog (NovoRapid) as needed to adequately control the blood glucose for a subject with Type 1 Diabetes can be maintained for a period of up to three days and if intradermal delivery of insulin has advantages over standard subcutaneous (under the skin) delivery.
Detailed description
The is a single center, open-label, 2 period crossover study randomized by route (intradermal versus subcutaneous) in patients with Type 1 diabetes. Subjects will receive their insulin, basal and bolus dosages, via intradermal (ID) and subcutaneous (SC) infusion sets over a three day period. Each subject will participate in 3 visits: a Screening Visit (V1), followed by 2 experimental intervention days (V2 and V3) to be started 2 - 21 days after screening visit. The minimum/maximum interval between study days shall be 5 to 28 days. Each subject will remain in the clinic for approximately 3 days during the experimental interventions. A final exam will be performed at the end of Visit 3. After successful screening and enrollment subjects are admitted to the clinic. Their insulin pump and infusion set is replaced by the investigational system, a commercially available insulin pump and either the intradermal infusion set (Research Catheter Set, BD) or the subcutaneous infusion set (Quick Set, Medtronic)to include an in-line pressure transducer/recorder and insulin NovoRapid. The initial pump infusion rate is established based on the patient's known basal infusion rate and the meal bolus insulin is estimated based on the patient's known insulin sensitivity. An intravenous (in the vein) catheter line is established, blood glucose is measured at least every 2 hours overnight and insulin corrections can be implemented, if deemed necessary. The overnight and pre-prandial (before meal) target range is 70-160 mg/dl, although the procedure will continue as planned if the patient is outside the range. It should be the goal not to give any IV glucose or insulin at all, and not to change basal insulin settings for at least 2 hours before the meal. The breakfast meal will be a high GI (60g carbohydrates) solid meal, to be consumed within 15 minutes and followed for a period of 6 hours of blood sampling for glucose and insulin levels. Lunch will be served as standardized mixed meal, and followed for a period of 4-6 hours. This procedure is repeated on days 2 and 3 whereas the breakfast and lunch meal as well as the insulin dose to cover the meal are the same. A light evening dinner is served every day, composition and insulin dose to be recorded. On day three after the 4 hour period following lunch the catheter will be removed, catheter and site assessments will be documented and an ultrasound observation of the infusion site (skin thickness and SC) versus an adjacent control site will be performed within 10 min after removal of the infusion set. Glucose rescue, if necessary, will be administered orally (juice, 200 mL). Insulin correction boli should be delivered via the investigational infusion set.
Interventions
DEVICESubcutaneous delivery via Medtronic Quick-Set
Infusion rates and pre-meal bolus doses will be based on subjects known daily infusion rate and subject's reported insulin to carbohydrate ratio.
DEVICEIntradermal delivery via the BD Research Catheter Set
Infusion rates and pre-meal bolus doses will be based on subjects known daily infusion rate and subject's reported insulin to carbohydrate ratio.
Sponsors
Becton, Dickinson and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Male and Female patients will be included in the trial only if they fulfill all the inclusion criteria mentioned below: * Understood and signed informed consent obtained before any trial-related activities (trial-related activities are any procedures that would not have been performed during normal management of the patient) * Type 1 Diabetes mellitus, according to clinical judgment / ADA / WHO-definition (Diabetes Care 2003; 26: 5-20) for at least 1 year. * Usage of insulin pump therapy (CSII) with carb counting for at least six months * Age in the range of ≥ 18 and ≤ 55 years * Body mass index (BMI) ≤ 32 kg/m² * HbA1c ≤ 8.0% at screening * Using ≤ than 60 U of insulin on a typical day (preferably) * Able and willing to adhere to the study procedures for the entire trial period * Negative test results for hepatitis C antibodies, hepatitis B surface antigen and HIV at screening.
Exclusion criteria
Patients will not be permitted to enter the trial, if they fulfill any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin levels | 0,10,15,20,25,30,35,40,45,50,55,60,65,70,80,90,120,150,180,210,240,300,330,345,360 minutes following each breakfast and lunch meal bolus for the 3 study days | Time to peak plasma concentration (Tmax) of insulin delivered intradermally as compared to insulin delivered subcutaneously after a meal bolus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Glucose | 0,10,15,20,25,30,35,40,45,50,55,60,65,70,80,90,120,150,180,210,240,300,330,345,360 minutes following each breakfast and lunch meal bolus for the 3 study days | Peak concentration of blood glucose (BGmax) during post meal excursions periods. Area under the plasma concentration versus time curve (AUC) of blood glucose during post meal excurion periods. |
| Device performance - adhesion | Evaluated at every timepoint a bolus injection is given | Adhesion (device remains attached to the skin) will be evaluated over the 3 day study period (adhered well, partially adhered, completely pulled off). |
| Skin thickness using ultrasound | Upon removal of the device (within 5 minutes) | Skin thickness will be measured at the infusion site and a control site using ultrasound |
| Insulin levels | 0,10,15,20,25,30,35,40,45,50,55,60,65,70,80,90,120,150,180,210,240,300,330,345,360 minutes following each breakfast and lunch meal bolus for the 3 study days | Comparison of peak plasma concentration (Cmax) of insulin, intradermally versus subcutaneously, during a meal bolus period. Comparison of area under the plasma concentration versus time curve (AUC), intradermally versus subcutanously, during a meal bolus period. |
| Device performance-pump alarm | over the 3 study days | The presence of an auditory alarm indicating an occlusion will be noted. |
| Skin effects-Draize Scoring for Skin Irritation | Following removal of the device (within 2 minutes) and 1 and 2 hours (+/- 5 minutes) post removal. | Local reaction at injection site will be scored using the Draize Scale 0-4 for redness and 0-4 for swelling. |
| Number of participants with adverse events | up to 53 days or until the subject is discharged, if sooner. | At each study contact, subjects will be questioned about any new or worsening undesirable events. |
| Device performance - Leakage of fluid (insulin) at injection site | Immediatley before and after each bolus injection and immediatly upon removal of the device at the end of the study period. | Immediatley before and after each bolus injection, the site will be observed for leakage (insulin). In addition, following removal of the device, if leakakge is observed, the fluid will be collected and quantified using a gravimetic method procedure. Leakage will be collected using a pre-weighed sterile absorbent swab, the swab will be re-weighed and the collected fuid volume calculated based on the density of the fluid. |
Countries
Germany
Outcome results
None listed