A Multi-centre Trial to Assess the Efficacy and Safety of the Omnipod 5 System in People With Type 2 Diabetes Undergoing Haemodialysis

Official title

An Open-label, Multi-centre, Randomised Controlled Trial to Assess the Efficacy, Safety and Utility of Automated Insulin Delivery in People With Type 2 Diabetes and Sub-optimal Glycaemia Undergoing Haemodialysis

Overview

Diabetes is the leading cause of kidney failure in the UK. Many people with diabetes and advanced kidney failure inject themselves with insulin and do finger-prick blood glucose tests. Managing diabetes in people with advanced kidney disease is challenging, with fluctuating glucose levels and an increased risk of unsafe low glucose levels. We now have continuous glucose monitors (CGM), which allow people to monitor glucose without painful fingerprick tests. CGM can be combined with insulin pumps to create automated insulin delivery systems (AID) that automatically deliver insulin to control glucose levels. AID systems are currently used in people with type 1 diabetes, but they are not used in people with type 2 diabetes. There is little information on how these systems might help people with diabetes and advanced kidney failure, and on dialysis. This study will investigate whether automated insulin delivery can improve glucose levels and quality of life in people with type 2 diabetes treated with more than one insulin injection with advanced kidney failure and undergoing regular haemodialysis treatment. This study will be conducted in four UK centres and will be of a parallel design. We estimate that the trial will require 84 participants to be recruited, and 76 participants to be randomised. We aim for 64 participants across both groups to complete the trial. Participants will wear a glucose sensor at the start. In random order, half will be randomised to AID treatment while the other half will continue usual care augmented with continuous glucose monitoring. The duration of each treatment stage is 12 weeks. The study will last about 18 weeks for each participant. We will compare the glucose levels in the AID group with the usual care group to see if there is a difference. Questionnaires and interviews will help us understand participants' experiences. We will carefully monitor the safety of the participants.

Interventions

• Device Omnipod 5
  Omnipod 5 automated insulin delivery system
• Device Insulin injections
  Usual insulin injections

Primary outcome measures

• Time in range 3.9 to 10 mmol/l [Time frame: 12 weeks]

Secondary outcome measures (10)

• Time spent below target glucose (<3.9mmol/l) [Time frame: 12 weeks]
• Time spent below target glucose (<3.0mmol/l) [Time frame: 12 weeks]
• Severe hypoglycaemic episodes [Time frame: 12 weeks]
• Frequency of significant ketosis events (ketones >1.5) [Time frame: 12 weeks]
• Diabetes Treatment Satisfaction Questionnaire Score [Time frame: 12 weeks]
• Quality of life (EQ-5D-5L) Score [Time frame: 12 weeks]
• Xerostomia Inventory (XI) Score [Time frame: 12 weeks]
• Type 2 Diabetes Distress Assessment System (T2-DDAS) Score [Time frame: 12 weeks]
• Frequency of significant ketosis events (ketones >3) [Time frame: 12 weeks]
• Dialysis Thirst Inventory (DTI) Score [Time frame: 12 weeks]

Eligibility criteria

Inclusion criteria

• Aged 18 years and older
• Participant has insulin-treated type 2 diabetes on more than 1 insulin injection per day or insulin pump therapy
• Participant has ESKD and is established on out-patient hospital-based haemodialysis treatment at least 3 times a week, via an arterio-venous fistula, graft or central venous catheter
• If the participant uses a CGM, the baseline time spent between 3.9 to 10 mmol/L in the last 4 weeks is <70%
• For those not using CGM screening HbA1c >7.0% (53 mmol/mol) and ≤ 12% (108 mmol/mol)
• Total daily dose of insulin is > 10 units and <200 units per day
• Literate in English for safe study conduct.
• Willing to wear study glucose sensors and the AID system
• Willing to follow study-specific instructions
• Female participants of childbearing age should be on effective contraception, not sexually active / or have no plans for pregnancy
• All patients whether transplant-wait listed or not, are eligible for inclusion.

Exclusion criteria

Exclusion criteria

• Any other physical disease or people with known severe mental illness (psychotic disorder, bipolar disorder, dementia, substance and alcohol dependence, learning disabilities, active suicidal ideation) that are likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
• Either current use of peritoneal dialysis or planned modality transfer (transplantation from a live donor with a confirmed date, peritoneal dialysis or conservative care) in the next 18 weeks
• Only treated with background (basal) insulin
• The participant is currently on AID or more than 2 weeks use of AID in the last 4 weeks
• Known or suspected allergy against insulin
• Treated with sulphonylureas (use of SGLT2 inhibitors are allowed)
• Treated with hydroxyurea (sensor interference)
• Presence of unstable retinopathy per Investigator's judgement
• Severe bilateral visual impairment
• Pregnancy, planned pregnancy in the next 3 months or breastfeeding current or planned glucocorticoid use other than inhaled/ topical use. Stable long-term steroid use is not an exclusion

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 4 centers

• Royal Derby Hospital — Derby
• Guys and St Thomas' Hospitals — London
• Hammersmith Hospital — London
• Manchester Royal Infirmary — Manchester

Publications

• Lu JC, Lee P, Ierino F, MacIsaac RJ, Ekinci E, O'Neal D. Challenges of Glycemic Control in People With Diabetes and Advanced Kidney Disease and the Potential of Automated Insulin Delivery. J Diabetes Sci Technol. 2024 Nov;18(6):1500-1508. doi: 10.1177/19322968231174040. Epub 2023 May 10. PMID 37162092

Identifiers

NCT: NCT07422532 · 173303 · NIHR207915

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗