Clinical Assessment of a Novel Microprobe Array Continuous Glucose Monitor for Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety and efficacy of the Imperial College Microprobe Array Continuous Glucose Sensor in healthy volunteers and in subjects with type 1 diabetes.

Detailed Description
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Continuous knowledge of ambient glucose levels will be of benefit to patients with T1DM, especially those with troublesome hypoglycaemia. Existing monitors require skin puncture to access interstitial fluid and sense its glucose content. Despite their clinical benefits, their use is associated with discomfort and their accuracy is questionable in hypoglycaemia. The development of a painless continuous glucose monitor is regarded as the top research priority by patients with diabetes. A novel continuous glucose monitoring device has been developed at Imperial College based on microprobe technology. It consists of a small, wearable patch ( 1 cm2), the size of a conventional postage stamp, containing microscopic projections (microprobes) that penetrate only the outermost skin layer. It accesses interstitial fluid to sense its glucose content without stimulating skin nerve fibres or reaching blood vessels within skin layers. The microprobe surface has the consistency of sandpaper. It is pushed into the skin with an applicator allowing it to penetrate through the skin layers and access the interstitial fluid in a minimally invasive manner. The device is disposable and optimum performance will be assessed over five days. The advantages of microprobe technology have been demonstrated in other clinical situations and include painless insertion, absence of bleeding and a low infection risk. The large surface area utilised in our microprobe device has the potential to improve device sensitivity and accuracy. Pre-clinical validation tests have demonstrated the ability of the device to respond accurately to variable glucose concentrations and to penetrate the outermost skin layer without fracture. We aim now to further develop the device through clinical studies in non-diabetic subjects and subjects with type 1 diabetes to allow painless accurate continuous glucose monitoring. The study will recruit 16 non-diabetic subjects and 20 subjects with type 1 diabetes. It will be conducted over four phases; oPhase 1 will assess safety, as a primary outcome, and efficacy, as a secondary outcome, in non-diabetic subjects over six hours in the clinical research facility where the device will be fitted and a cannula inserted for venous sampling every 15 minutes to measure venous blood glucose (YSI). Safety will be assessed with regards to skin inflammation and pain. Efficacy will be assessed in this phase by assessing magnitude of current measured by the microprobe array sensor and comparison of measured ISF glucose concentrations to simultaneous venous blood glucose samples (YSI). oPhase 2 will also assess safety, as a primary outcome, and efficacy, as a secondary outcome, in non-diabetic subjects over a period of 24 hours. The first six hours in the clinical research facility (same as phase 1), then subject will be allowed to go home with the device to assess safety over that period. oPhase 3 aims to assess efficacy of the device as a primary outcome and safety as a secondary outcome. This will be in subjects with type 1 diabetes over 24 hours as inpatients. Efficacy will be assessed mechanically (by the ability to penetrate the stratum corneum) and functionally (by the ability to accurately sense ISF glucose). The derived ISF glucose levels will be compared with simultaneous venous glucose samples (YSI) and with a commercially available CGM device (iPro2, Medtronic). Assessment of microprobe penetration of the stratum corneum will be performed using confocal microscopy, optical coherence tomography and in skin biopsies. oPhase 4 aims to assess efficacy of the device as a primary outcome and safety as a secondary outcome. This will be in subjects with type 1 diabetes over 5 days in ambulatory situation. Efficacy will be assessed by comparing microprobe sensor derived ISF glucose levels against ISF glucose levels measured using a commercially available CGM device (iPro2, Medtronic).

Official Title
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Clinical Assessment of a Novel Microprobe Array Continuous Glucose Monitor for Type 1 Diabetes

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Device: Microprobe glucose sensor


Participation Criteria
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Eligibility Criteria
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For phases 1 and 2: Inclusion Criteria: • Adults over 18 years of age Exclusion Criteria: History of upper limb neuropathy or radiculopathy History of pre-existing skin condition Pregnant or planning pregnancy in next 12 months Breastfeeding Enrolled in other clinical trials uncontrolled concurrent illness Have active malignancy or under investigation for malignancy For phases 3 and 4: Inclusion Criteria: Adults over 18 years of age. Diagnosed with Type 1 diabetes for greater than 1 year. HbA1c less than or equal to 9.0 % (75 mmol/mol). Registered with a General Practitioner. Exclusion criteria: History of diabetic dermopathy or pre-existing skin condition History of upper limb neuropathy or radiculopathy Pregnant or planning pregnancy in next 12 months Breastfeeding Enrolled in other clinical trials uncontrolled concurrent illness physical or visual impairment preventing sensor's use Have active malignancy or under investigation for malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Microprobe Glucose Sensor Phase 1<br>The microprobe array continuous glucose sensor will be applied to healthy volunteers for 6 hours | Device: Microprobe glucose sensor<br>* Assessment of safety and accuracy of a novel continuous glucose monitor based on microprobe technology.<br>* Other names: Microprobe Array Continuous Glucose Monitor;|
| Experimental: Microprobe Glucose Sensor Phase 2<br>The microprobe array continuous glucose sensor will be applied to healthy volunteers for 24 hours | Device: Microprobe glucose sensor<br>* Assessment of safety and accuracy of a novel continuous glucose monitor based on microprobe technology.<br>* Other names: Microprobe Array Continuous Glucose Monitor;|
| Experimental: Microprobe Glucose Sensor Phase 3 and 4<br>The microprobe array continuous glucose sensor will be applied to participants with type 1 diabetes | Device: Microprobe glucose sensor<br>* Assessment of safety and accuracy of a novel continuous glucose monitor based on microprobe technology.<br>* Other names: Microprobe Array Continuous Glucose Monitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participant Developed the Skin Inflammation | The study aims to assess safety of the use of microprobe array continuous glucose sensor with regards to skin inflammation. | 24 hours | 
| Difference to the Venous Blood Glucose MARD | Phase 3 of the study aim to assess efficacy of the device in people with type 1 diabetes. This will be done in comparison to venous blood glucose using YSI machine in a controlled environment over 24 hours (phase 3). it was originally planned to then compare this to ISF glucose in ambulatory situation over five days (phase 4) however phase 4 did not go ahead. Measured using mean absolute relative difference with respect to venous blood glucose | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Score | The study aims to assess safety of the device with regards to pain degree in comparison to venflon insertion and insertion of an existing continuous glucose monitor (Medtronic iPro2 CGM system, Northridge, California). This will be done at each phase of the four study phases. | 24 hours | 
| Number of Participant Developed Skin Penetration | This done using Optical Coherence Tomography and Confocal Microscopy. Measure = variation in penetration depth of microprobe needles over 24 hours | 24 hours | 
| Detectable Signal | This is a secondary outcome for phases 1 & 2. | 24 hours | 
| Correlation With Venous Blood Glucose | This is a secondary outcome for phases 1 and 2. It is a primary outcome for phase 3. Using MARD. | 24 hours | 
| Acceptability Questionnaire | This is a secondary outcome for phases 3 and 4. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Continuous Glucose Monitoring, Microprobes