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

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.

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).

Eligibility Criteria:
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