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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Device: Microprobe glucose sensor

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1PG
    • Imperial College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Desmond Johnston, PhD, FRCP, Professor of Diabetes & Endocrinology - Imperial College London

Publications and helpful links

General Publications

• Pickup JC, Freeman SC, Sutton AJ. Glycaemic control in type 1 diabetes during real time continuous glucose monitoring compared with self monitoring of blood glucose: meta-analysis of randomised controlled trials using individual patient data. BMJ. 2011 Jul 7;343:d3805. doi: 10.1136/bmj.d3805.
• Battelino T, Phillip M, Bratina N, Nimri R, Oskarsson P, Bolinder J. Effect of continuous glucose monitoring on hypoglycemia in type 1 diabetes. Diabetes Care. 2011 Apr;34(4):795-800. doi: 10.2337/dc10-1989. Epub 2011 Feb 19.
• El-Laboudi A, Oliver NS, Cass A, Johnston D. Use of microneedle array devices for continuous glucose monitoring: a review. Diabetes Technol Ther. 2013 Jan;15(1):101-15. doi: 10.1089/dia.2012.0188. Epub 2012 Dec 12.
• Khanna P, Strom JA, Malone JI, Bhansali S. Microneedle-based automated therapy for diabetes mellitus. J Diabetes Sci Technol. 2008 Nov;2(6):1122-9. doi: 10.1177/193229680800200621.
• Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group; Tamborlane WV, Beck RW, Bode BW, Buckingham B, Chase HP, Clemons R, Fiallo-Scharer R, Fox LA, Gilliam LK, Hirsch IB, Huang ES, Kollman C, Kowalski AJ, Laffel L, Lawrence JM, Lee J, Mauras N, O'Grady M, Ruedy KJ, Tansey M, Tsalikian E, Weinzimer S, Wilson DM, Wolpert H, Wysocki T, Xing D. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med. 2008 Oct 2;359(14):1464-76. doi: 10.1056/NEJMoa0805017. Epub 2008 Sep 8.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: July 23, 2013
• First Submitted That Met QC Criteria: July 23, 2013
• First Posted (Estimate): July 25, 2013

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes; Continuous Glucose Monitoring; Microprobes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: 13SM0639

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No