Time-In-Range Based Risk Stratification of Type 2 Diabetes Microvascular Complications

Type 2 Diabetes Clinical Trial

— TRACK2  

Official title:

Time-in-Range (TIR), a Novel Continuous Glucose Monitoring (CGM) Based Measure, to Improve Risk Stratification of Microvascular Complications in Type 2 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05787990
• Other study ID #: CNIG20nov-0005
• Status: Recruiting
• Start date: October 14, 2021
• Est. completion date: December 2024

Study information

• Verified date: April 2023
• Source: Singapore General Hospital
• Contact: Suresh Rama Chandran, MD, MRCP(UK)
• Phone: +6563264654
• Email: suresh.rama.chandran[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to learn about the role of Time-in-Range to stratify the risk of micro vascular complications in adults with type 2 diabetes. The main questions it aims to answer are:

1. Is a lower Time-in-Range associated with a higher risk of diabetes microvascular complications, independent of HbA1c?

2. Is Time-in-Range lower among sulfonylurea and premixed insulin therapy users compared to non-sulfonylurea and non-premixed insulin therapy users, respectively.

Description:

Methods/Approach

Participants: Investigators aim to recruit a maximum of 500 adults with type 2 diabetes on medical therapy with an HbA1c between 6-12%. Pregnant women, people undergoing active cancer therapies, people taking oral or injectable steroids and those with chronic kidney disease on dialysis will be excluded as the glycemic profile and the pathology in these patients are significantly different from a typical adult with type 2 diabetes. Stratified recruitment will aim to achieve a minimum number in the four major therapy classes to ensure a heterogeneous and representative sample.

1. Oral drugs ± basal insulin not using sulfonylureas (50-200)

2. Oral drugs ± basal insulin using sulfonylureas (50-200)

3. Insulin replacement using premixed insulin therapy (50-200)

4. Insulin replacement using basal-bolus insulin therapy (50-200)

Baseline assessment

At baseline, detailed medical history and anthropometry will be collected from the participants, and participants will have their HbA1c measured, and glycaemia characterized using a blinded CGM. Blood and urine (if required) will be collected for HbA1c and Albumin-creatinine ratio, respectively. HbA1c test results, if available within 6 weeks and Urine Microalbumin-Creatinine Ratio, if available within 6 months from the date of recruitment will be deemed sufficient and no further tests will be done as part of the research. Neuropathy will be assessed by a non-invasive foot exam with a 10g monofilament and neurothesiometer.

Ophthalmological Assessment

Intra-ocular pressure assessment to check for Glaucoma, Administration of Mydriatic eye drop to dilate the eyes, Retinal fundus photograph, In-vivo corneal confocal microscopy, optical coherence tomography and tear sample collection will be performed at Singapore Eye Research Institute (SERI). Optical coherence tomography and in-vivo corneal confocal microscopy are novel non-invasive techniques that can quantify the ocular degenerative changes in people with diabetes. Importantly these techniques are sensitive enough to detect changes in retinal layers and corneal nerve fibre densities even before signs of overt diabetes retinopathy. Diabetic corneal neuropathy has been considered as the surrogate marker for diabetic peripheral neuropathy.

Images generated form the ophthalmological examinations will be analysed using proprietary software and the data used to study the relation between glycaemia and diabetes complications.

For tear sample collection a standardized strip of filter paper will be placed in the lower lateral fornix for 5 mins.

Medical history

Demographics, diabetes related history, current and past medical therapy, past history of microvascular and macrovascular complications, associated metabolic diseases, admissions, and historical HbA1c readings up to 10 years before will be collected. The above data, where required will be retrieved either from the participants or from the electronic medical records of Singapore General Hospital.

Quantifying Time-in-Range (TIR) using Continuous glucose monitoring.

TIR will be measured in the eligible subjects by continuous glucose monitoring method using a blinded continuous glucose sensor. Subjects will be blinded to the glucose readings and will wear the sensor for two weeks, after which data from the sensor will be downloaded for analysis. If the glucose sensor falls off before 7 days or is retrieved with less than 7 full days of data, the participant will wear a second and final continuous glucose monitoring sensor to record glycemic data. Participants will also answer a short survey on their experience of wearing the sensor.

CGM Data: The blinded CGM will generate 1344 glucose readings over two weeks per participant (one reading every 15 minutes). This data will be downloaded and analyzed to calculate various glucose parameters, including percentage Time-in-Range. Time-in-Range is calculated as the percentage of readings within the target range of 3.9-10 mmol/L.

Patient reported outcomes: Data regarding the user experience of the continuous glucose monitoring will be collected using a short survey (included in Data collection form). Other diabetes related patient reported outcomes will be collected from the SGH EMR retrospectively and prospectively to study the impact of glycaemia and diabetes complications on diabetes related patient reported outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes,

• Age >= 21 years,

• Ability to provide informed consent,

• HbA1c done within 6 months of recruitment between 6-12%

Exclusion Criteria:

• Undergoing active chemotherapy or immunotherapy for cancer

• Currently taking oral or injectable steroids

• Chronic kidney disease on dialysis

• Women who are pregnant or breastfeeding

Related Conditions & MeSH terms

• Diabetes Complications
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes Related Complications
• Diabetes; Nephropathy (Manifestation)
• Diabetes; Neuropathy, Polyneuropathy (Manifestation)
• Diabetic Nephropathies
• Polyneuropathies
• Type 2 Diabetes

Intervention

Diagnostic Test:
• Diabetes Microvascular Complication Tests
Continuous glucose monitoring using Freestyle Libre Pro, Foot examination with monofilament and neurothesiometer, HbA1c and Urine Microalbumin Creatinine Ratio, Corneal confocal microscopy, Fundal photography, Optical coherence tomography, Optical cohere

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
Singapore General Hospital	Singapore Eye Research Institute

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of Diabetes Retinopathy	Based on Fundal Photography grading	10 years
Primary	Presence of Diabetes Neuropathy	Based on 10g monofilament foot examination	10 years
Primary	Presence of Diabetes Nephropathy	Urine microalbumin-creatinine ratio in mg/g	10 years
Secondary	Continuous glucose monitoring derived glycemic variables	Time-in-Range (70-180 mg/dl)	14 days
Secondary	Severity of Retinal degenerative changes	Based on Optical coherence tomography	10 years
Secondary	Severity of corneal neuropathy	Based on confocal corneal microscopy	10 years
Secondary	Severity of diabetes peripheral neuropathy	Vibration threshold on neurothesiometer	10 years