Quantifying Artificial Pancreas-related Changes in Diabetic Neuropathy

Study Overview
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Brief Summary
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A complication of diabetes mellitus is damage to nerves called neuropathy. There are several mechanisms involved that will lead to the development of neuropathy. Neuropathy can lead to foot ulcers, infections and amputations. Patients with neuropathy may also experience pain, which can be difficult to control and the medications are limited by side effects. Despite this there are no approved treatments to reverse the progression of neuropathy and the management of patients is focused on controlling blood glucose and other metabolic factors to prevent neuropathy and its symptoms from getting worse. Patients with type 1 diabetes are prescribed multiple daily injections (MDI) of insulin to manage their glucose control. However, insulin pump therapy and, more recently, automated insulin delivery (AID) or the Artificial Pancreas can be used as the insulin delivery method for patients with type 1 diabetes mellitus. Manchester Diabetes Centre is the first adult diabetes centre in Europe to pioneer and use a commercially-approved AID in clinical practice. Insulin pump therapy and AID have the advantage of being able to provide insulin at variable doses, which is closer to the natural process occurring within an individual without diabetes. Both are currently considered to be the most physiological method of insulin delivery and have been shown to improve glycaemic control, quality of life (QOL) and reduce the risk of hypoglycaemia (low blood glucose level). The investigators have previously shown in a small group of people that use of an insulin pump therapy may improve symptoms of painful neuropathy via a more stable glucose profile. The peaks and drops in insulin may make neuropathy worse. In this study the investigators aim to investigate the use of insulin pump therapy and AID in their effect on neuropathy. This will be in comparison to a control group of patients on MDI. The investigatorsbwill use a variety of neuropathy measures and symptom questionnaires to assess structural and functional neuropathy status. The investigators hypothesise that those patients receiving the newer technologies will demonstrate an improvement in symptoms and nerve regeneration. This finding would have a significant impact for patients as it would provide evidence to suggest that those patients with neuropathy should be put onto an insulin pump or AID to improve neuropathy and its symptoms. As these are treatments that are already available on the NHS to patients satisfying specific criteria this study aims to show benefit in this cohort of patients which can be implemented immediately in clinical practice.

Official Title
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A Longitudinal, Single Centre Study to Assess the Effects of Artificial Pancreas-related Changes in Diabetic Neuropathy

Conditions
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Diabetes Complications, Diabetes Mellitus, Type 1, Diabetic Neuropathies

Intervention / Treatment
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* Device: Hybrid Closed Loop Insulin Pump


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes aged 18-70 who falls into either of these three categories and has the ability to read and comprehend English: Starting Artificial Pancreas therapy as determined for clinical need Starting insulin pump therapy as determined for clinical need On multiple daily injection therapy for insulin delivery Exclusion Criteria: History of ocular disease that may affect the cornea. History of corneal trauma or surgery (NB cataract surgery does not preclude enrolment unless surgery occurred in the 3 months prior to enrolment date) Concurrent ocular disease, infection or inflammation. History of neuropathy due to alcoholism, renal impairment requiring renal replacement therapy, infectious disease (e.g., Lyme disease, HIV/AIDS, hepatitis B), liver failure, B12 deficiency Unable to read and comprehend English

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: MDI<br>All participants will have: Continuous Glucose Monitoring Neuropathy Assessments and Pain Questionnaires ACR, Blood Tests | |
| Active Comparator: Artificial Pancreas - Closed Loop<br>All participants will have: Continuous Glucose Monitoring Neuropathy Assessments and Pain Questionnaires ACR, Blood Tests | Device: Hybrid Closed Loop Insulin Pump<br>* As above<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Change in Corneal nerve fibre density (CNFD) | Corneal nerve fibre density (CNFD) | 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathy symptom profile | Symptoms of painful neuropathy measured using the neuropathic pain symptom inventory scale | 6 and 12 months. Min value 0, max value 38. Higher score suggests a worse outcome | 
| Neuropathy disability score | Neuropathy disability score | 6 and 12 months Min value 0, max value 10. Higher score suggests a worse outcome | 
| Quality of life questionnaire | Quality of life Short Form -36 scale measurement | 6 and 12 months Min value 0, max value 36. Higher score suggests a worse outcome | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes