QT Interval Abnormalities in Sulfonylurea Treated Type 2 Diabetes: Relationship to Treatment Induced Hypoglycaemia

NCT02298803 | Completed Results

• 1 other identifier: X14 0314
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Hypoglycaemia is the most common acute complication of diabetes and can limit therapeutic efforts to improve glycaemic control. It is a potential side effect of drugs used to treat diabetes, particularly with the use of sulfonylurea (SU) treatment. It has been demonstrated that hypoglycaemia causes the prolongation of corrected QT (QTc) interval, which is associated with ventricular arrhythmias and sudden death. Hypoglycaemia in T2DM has recently come into focus with the results of the ACCORD, ADVANCE and VADT trials. In this study, the investigators aim to examine the association of hypoglycaemia and glucose fluctuations on QT-interval and QT variability in patients with type 2 diabetes treated with SU. Patients will be studied using simultaneous Continuous Glucose Monitoring (CGM) and ambulatory ECG monitoring (Holter). Study participants will be recruited from the Diabetes Centre, RPAH or from specialist consulting rooms. They will be required to attend the Diabetes Centre on two occasions. At the first visit, blood will be collected and CGM and Holter monitoring commenced. At Visit 2, i.e. two days later, the patient will return to the Diabetes Centre to have the equipment removed. The data obtained from the CGM and Holter monitor will then be downloaded for review and analysis.

Conditions

Diabetes Related Complications

Outcome Measures

Primary Outcomes (2)

• Change in the Corrected QT-interval During Nocturnal Hypoglycemia

  The nocturnal time period for the study spanned from 11 pm in the evening until 7 am the following morning on two consecutive days. The change in the corrected QT interval during nocturnal hypoglycemia was determined by calculating the difference between the average QTc interval length during periods of hypoglycemia (blood glucose level \<3.5 mmol/L) and the average QTc interval length during periods of normoglycemia (blood glucose level \>3.5 mmol/L) for the nocturnal time period. The average QTc interval was calculated using an individually optimised correction formula. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was positive, the participant experienced QTc prolongation during hypoglycemia. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was negative, the participant experienced QTc shortening during hypoglycemia.

  Nocturnal time period (2300-0700) during the 48 hours of Holter monitoring

• Change in Corrected QT Interval During Day Time Hypoglycaemia

  The day time period for the study spanned from 7 am in the morning until 11 pm in the evening on two consecutive days. The change in the corrected QT interval during day time hypoglycemia was determined by calculating the difference between the average QTc interval length during periods of hypoglycemia (blood glucose level \<3.5 mmol/L) and the average QTc interval length during periods of normoglycemia (blood glucose level \>3.5 mmol/L) for the day time period. The average QTc interval was calculated using an individually optimised correction formula. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was positive, the participant experienced QTc prolongation during hypoglycemia. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was negative, the participant experienced QTc shortening during hypoglycemia.

  Day time period (0700-2300) during the 48 hours of Holter monitoring

Secondary Outcomes (3)

• Pearson's Correlation Coefficient of Delta QTc and a Measure of Glucose Variability, MAGE (Mean Amplitude of Glycemic Excursion).

  Nocturnal time period (2300-0700) during the 48 hours of Holter monitoring

• Mean Amplitude of Glycemic Excursion (MAGE)

  48 hours of continuous glucose monitoring

• deltaQTc

  Nocturnal time period (2300-0700) during the 48 hours of Holter monitoring

Study Arms (1)

Holter and Glucose monitoring

OTHER

In this study the interventions will be the simultaneous monitoring of glucose and QT interval via a subcutaneous continuous glucose monitor and a Hoter monitor, respectively.

Device: Holter and Glucose monitoring

Interventions

Holter and Glucose monitoring DEVICE

(i) Continuous Glucose Monitoring A sterile disposable glucose-sensing sensor will be inserted into the subcutaneous tissues in either the abdomen or the upper outer quadrant of the patient's buttock. This sensor automatically measures the change in glucose in interstitial fluid every 5 minutes. The monitor will be worn for two days. (ii)Holter Monitoring The Holter monitor to capture cardiac conduction, specifically QT interval, will be worn for the same period as the continuous glucoe monitor with study participants encouraged to perform regular daily activities.

Holter and Glucose monitoring

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes
• A history of symptomatic or documented hypoglycaemia
• Currently treated with a sulphonylurea ± any anti-diabetic agent/s other than insulin
• Currently performing home blood glucose monitoring and willing to do seven tests a day during the study period

You may not qualify if:

• Type 1 diabetes
• Current treatment with insulin
• LBBB and conduction anomalies that preclude QT analysis
• Drugs that prolong QT interval
• Family history of Long QT syndrome

Sponsors & Collaborators

• Royal Prince Alfred Hospital, Sydney, Australia: lead
• Merck Sharp & Dohme LLC: collaborator

Related Publications (5)

• Chugh SS, Reinier K, Singh T, Uy-Evanado A, Socoteanu C, Peters D, Mariani R, Gunson K, Jui J. Determinants of prolonged QT interval and their contribution to sudden death risk in coronary artery disease: the Oregon Sudden Unexpected Death Study. Circulation. 2009 Feb 10;119(5):663-70. doi: 10.1161/CIRCULATIONAHA.108.797035. Epub 2009 Jan 26.

  PMID: 19171855 BACKGROUND

• UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007 Jun;50(6):1140-7. doi: 10.1007/s00125-007-0599-y. Epub 2007 Apr 6.

  PMID: 17415551 BACKGROUND

• Cleveland JC Jr, Meldrum DR, Cain BS, Banerjee A, Harken AH. Oral sulfonylurea hypoglycemic agents prevent ischemic preconditioning in human myocardium. Two paradoxes revisited. Circulation. 1997 Jul 1;96(1):29-32. doi: 10.1161/01.cir.96.1.29.

  PMID: 9236412 BACKGROUND

• Maia FF, Araujo LR. Efficacy of continuous glucose monitoring system (CGMS) to detect postprandial hyperglycemia and unrecognized hypoglycemia in type 1 diabetic patients. Diabetes Res Clin Pract. 2007 Jan;75(1):30-4. doi: 10.1016/j.diabres.2006.05.009. Epub 2006 Jun 27.

  PMID: 16806560 BACKGROUND

• Piccirillo G, Rossi P, Magri D. The QT variability index: a multidimensional approach to understanding cardiovascular disease. Cardiology. 2011;118(1):42-4. doi: 10.1159/000324476. Epub 2011 Mar 11. No abstract available.

  PMID: 21411996 BACKGROUND

MeSH Terms

Conditions

Diabetes Complications

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Endocrine System Diseases

Results Point of Contact

• Title: Dr Ted Wu
• Organization: Diabetes Centre, Royal Prince Alfred Hospital

ted.wu@sswahs.nsw.gov.au

61295155888

Study Officials

• Ted Wu, MBBS, PhD

  Royal Prince Alfred Hospital, Sydney, NSW, Australia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 24, 2014
• Study Start: January 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: February 28, 2018
• Results First Posted: February 28, 2018

Record last verified: 2018-01