The PLGS clinical trial is investigating a Predictive Low Glucose Suspend feature on insulin pumps. This feature uses a mathematical algorithm to analyse data from a continuous glucose monitor (CGM) inserted under the skin. When the algorithm predicts that blood glucose levels may drop too low in the near future, insulin delivery via the pump is automatically shut off, preventing the hypoglycemic episode from ever occurring.

The PLGS feature is another step closer to the development of an artificial pancreas. It aims to enable people with type 1 diabetes to maintain their blood glucose at a level as close to normal as possible, by reducing the risk and the fear of hypoglycaemia.

PLGS study is a multi-centre clinical trial being conducted in five major tertiary hospitals around Australia. The aim of the study is to test how well the algorithm is able to safely predict and prevent hypoglycaemia when challenged by exercise and other lifestyle factors, and to establish how long insulin should be suspended following a predicted episode of hypoglycaemia.

To find out about how you can participate in this project, contact: Charles Czank, Charles.Czank@telethonkids.org.au

Full Detail About This Clinical Trial

Technical Summary

The Predictive Low Glucose Suspend study is a Phase II clinical trial investigating the safety and effectiveness of a system that suspends insulin delivery when hypoglycaemia is predicted and resumes insulin delivery after suspension. The intervention involves continuous subcutaneous insulin infusion with real-time continuous glucose monitoring system and predictive low glucose suspend feature (Medtronic Minimed 640G) for six months duration.

The current study has 2 stages; an initial in-clinic stage to test the safety and efficacy of the algorithm, and to assist in the planning of pump resumption in the next phase of proposed studies (completed in 2014), followed by  a randomised controlled trial at home which will be a world-first in the usage of a portable Predictive Low Glucose Suspend System. The participants will wear the pump with the system on or off for a period of 5 months. If effective and safe it is likely to reduce the burden of diabetes care as well as allow more intensive attempts to improve glycemic control. It will also represent a next step to closed-loop control.

In addition there is also a clamp sub-study to investigate counter-regulatory hormone response of participants. This addresses an important scientific question as impaired hypoglycaemia awareness is a major problem in diabetes therapy, leading to greater risk of severe hypoglycaemia which limits the ability to achieve good glycaemic control and significantly impairs quality of life for those affected. Any restoration or improvement in hypoglycemia awareness and hormonal responses will have significant impacts on quality of life and diabetes management. 

Trial Design
  1. In the first stage in-clinic studies will be conducted to determine whether the algorithm prevents hypoglycaemia using experimental protocols to induce hypoglycaemia. Two modes of inducing hypoglycaemia will be employed and compared: exercise and increased insulin delivery. By monitoring the glucose and ketone levels post suspension and insulin resumption we will determine the optimal time and conditions to reinstate insulin delivery and the safety margins of this resumption of insulin delivery.
  2. With the parameters gained from stage 1, a randomized controlled trial with 150 trial participants will be performed comparing RT-CGMS with insulin pump to RT-CGMS with insulin pump plus predictive low glucose suspend (PLGS) algorithm. The main outcome measure will be time spent in hypoglycemia.
  3. Questionnaires to investigate the psychosocial impact of this predictive suspend technology on the participants and their families as well.
  4. Counter-regulatory hormone response assessment to investigate the impact of this predictive suspend technology on counter-regulatory hormones and hypoglycaemia awareness. 
Principal Investigators
  • Professor Timothy Jones, Princess Margaret Hospital, Perth
Funder

The Australian Type 1 Diabetes Clinical Research Network, JDRF

Locations
  • Princess Margaret Hospital For Children, Perth WA
  • Children’s Hospital at Westmead, Sydney NSW
  • Royal Children’s Hospital, Murdoch Children’s Research Institute, Parkville VIC
  • John Hunter Children’s Hospital, New Lambton Heights NSW
  • Women’s and Children’s Hospital, Adelaide SA
Primary Endpoint

To compare the average percent  time spent in the hypoglycaemic range  during 6 months of therapy with the insulin pump and predictive low glucose insulin suspend algortithm compared to standard sensor augmented insulin pump therapy.

Secondary Endpoints

To compare the events of hypoglycaemia, defined as 20 minutes or more with sensor glucose < 3.5mmol/l, during 6 months of therapy with insulin pump and predictive low glucose insulin suspend compared to standart sendor augmented insulin pump therapy. 

To determine the counterregulatory hormone response and adrenergic responses to hypoglycaemia, as measured during hyperinsulinaemic hypoglycaemic clamp study in participants with hypoglycaemia unawareness.

To determine patient satisfaction and acceptability assessed by a Pump Satisfaction Questionnaire and to measure the impact of the intervention on patient’s quality of life and fear of hypoglycaemia as assessed by Quality of Life Questionnaire (EQ-5Dy), the Fear of Hypoglycaemia and Hypoglycaemia Awareness questionaire.

Inclusion/Exclusion

Inclusion Criteria

  • Patients diagnosed with type 1 diabetes for at least 12 months
  • Participants aged 8 to 20 years
  • Participants on an insulin pump and have a HbA1c below 10%

Exclusion Criteria

  • Adrenal insufficiency/Growth hormone insufficiency
  • Pregnant or lactating women
  • Any additional condition(s) that in the investigator’s opinion would warrant exclusion from the study or prevent the subject from completing the study
Anticipated Outcomes

The capacity to suspend insulin delivery when impending hypoglycaemia is predicted offers the advantage of reducing the actual time spent hypoglycemic. If effective and safe it is likely to reduce the burden of diabetes care as well as allow more intensive attempts to improve glycemic control. It will also represent a next step to closed-loop control.

Start/End Date

June 2014 - December 2015 (Clinical Trial)

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 Photo: Australian researchers working on the PLGS trial.