Closed-loop Control of Postprandial Glucose Levels in Children and Adults With Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

An Open-label, Randomized, Five-way, Cross-over Study to Compare the Efficacy of Single- and Dual-hormone Closed-loop Operations Combined With Either Conventional Carbohydrate Counting or a Simplified Qualitative Meal-size Estimation, and Sensor-augmented Pump Therapy in Regulating Glucose Levels in Children and Adults With Type 1 Diabetes

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02490098
• Other study ID #: CLASS-13
• Status: Withdrawn
• Phase: Phase 2
• First received: July 1, 2015
• Last updated: October 25, 2017
• Start date: January 2018
• Est. completion date: July 2018

Study information

• Verified date: October 2017
• Source: Institut de Recherches Cliniques de Montreal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Current intensive insulin therapy in T1D involves prandial insulin boluses depending on the carbohydrate content of each ingested meal. Carbohydrate content of ingested meals is the main determinant of post-meal glucose excursion. Therefore, accurate carbohydrate counting is a critical aspect of managing postprandial blood glucose levels in type 1 diabetes in order to avoid too much or too little insulin resulting in hypoglycemia and hyperglycemia, respectively. Precision of carbohydrate counting is associated with better glycemic control. However, accurate carbohydrate counting is a challenging task for many patients with type 1 diabetes. Recent developments of continuous glucose sensors and insulin infusion pumps have motivated the research toward "closed-loop'' strategies to regulate glucose levels in patients with type 1 diabetes. In a closed-loop strategy, the pump insulin infusion rate is altered based on a computer generated recommendation that rely on continuous glucose sensor readings. A dual-hormone closed-loop strategy has also been recently proposed to regulate glucose levels. In a dual-hormone strategy, subcutaneous insulin delivery is accompanied by subcutaneous glucagon infusion. Postprandial meal glucose control with closed-loop strategy still needs some improvements. The objective of this study is to test in outpatient unrestricted settings whether, in the context of closed-loop strategy, conventional meal carbohydrate counting could be reduced to a simplified qualitative meal size estimation without a significant degradation in overall glycemic control in children and adult patients with type 1 diabetes. The investigators hypothesize that 1) dual-hormone closed-loop strategy with qualitative meal size estimation is equivalent to dual-hormone closed-loop strategy with CHO counting in terms of mean glucose; 2) single-hormone closed-loop strategy with qualitative meal size estimation is equivalent to single-hormone closed-loop strategy with CHO counting in terms of mean glucose;

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

Inclusion Criteria:

1. Males and females = 8 years old.

2. Clinical diagnosis of type 1 diabetes for at least one year.

3. The subject will have been on insulin pump therapy for at least 3 months and currently using a fast actin insulin analog (Lispro, Aspart or Guilisine).

4. Last (less than 3 months) HbA1c = 10%.

5. Currently using carbohydrate counting as the meal insulin dose strategy.

6. Live in the area of Montreal

Exclusion Criteria:

1. Clinically significant microvascular complications: nephropathy (estimated glomerular filtration rate below 40 ml/min), neuropathy (especially diagnosed gastroparesis) or severe proliferative retinopathy as judged by the investigator.

2. Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.

3. Pregnancy.

4. Severe hypoglycemic episode within 1 month of screening.

5. Agents affecting gastric emptying (Motilium®, Prandase®, Victoza®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, SGLT-2 inhibitors and DPP-4 inhibitors) if not at a stable dose for 3 months. Otherwise, these medications are acceptable and will be kept stable during the entire protocol.

6. Oral steroids unless patients present a low stable dose (e.g. 10 mg or less of prednisone per day or physiological doses, less than 35 mg/day, of hydrocortisone Cortef®). Inhale steroids at stable dose in the last month are acceptable.

7. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator (e.g. unstable psychiatric condition).

8. Failure to comply with team's recommendations (e.g. not willing to change pump parameters, follow algorithm's suggestions, etc).

9. Living or planned travel outside Montreal (> 1h of driving) area during closed-loop procedures.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Other:
• 6-day intervention with sensor-augmented pump therapy
One day prior to the intervention, participants will have to install a glucose sensor and the study insulin pump. Participants will adjust their insulin delivery as per their standard practice; including temporary basal and correction boluses. Participants will have access to their finger-stick glucose measurements and will be advised to measure their glucose level as per their standard practice. Participants will be asked to install a new infusion set every 2 days. Participants will be allowed to eat whatever they want and allowed to drink alcohol. Participants will use sensor-augmented pump therapy for 6 days.
• 6-day intervention with single-hormone closed-loop strategy
One day prior to the intervention, participants will have to install a glucose sensor and the study insulin pump. On the first day of the intervention, participants will be admitted to the clinical research facility in the morning. A team member will review with the participant how to use study devices. Competency on the use of study devices will be assessed by a team member. Only participants demonstrating competency on use of study devices will be allowed to continue to the home study phase. Participants will be allowed to go home in the afternoon. They will be advised to continue with study intervention at home for the next 5 days. Participants will be asked to install a new infusion set every 2 days. Participants will be allowed to eat whatever they want and allowed to drink alcohol.
• 6-day intervention with dual-hormone closed-loop strategy
One day prior to the intervention, participants will have to install a glucose sensor and the study insulin pump. On the first day of the intervention, participants will be admitted to the clinical research facility in the morning. Participants will have to install a second pump containing glucagon. A team member will review with the participant how to use study devices. Competency on the use of study devices will be assessed by a team member. Only participants demonstrating competency on use of study devices will be allowed to continue to the home study phase. Participants will be allowed to go home in the afternoon. They will be advised to continue with study intervention at home for the next 5 days. Participants will be asked to install a new infusion set every 2 days. Participants will be allowed to eat whatever they want and allowed to drink alcohol.

Drug:
• Insulin
Participant's usual fast-acting insulin analog will be used: Lispro (Humalog), Aspart (NovoRapid) or Glulisine (Apidra)
• Glucagon
Glucagon (Eli Lilly) will be used during dual-hormone closed-loop strategy.

Device:
• Continuous Glucose Monitoring System Enlite sensor®, Medtronic
Enlite sensor®, Medtronic
• Insulin pump MiniMed® Paradigm® Veo™, Medtronic
MiniMed® Paradigm® Veo™, Medtronic

Locations

Country	Name	City	State
Canada	Institut de recherches cliniques de Montréal	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Cliniques de Montreal	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean day-and-night glucose levels		6 days
Secondary	Percentage of time of glucose levels between 4.0 and 8.0 mmol/L		6 days
Secondary	Percentage of time of glucose levels between 4.0 and 10.0 mmol/L		6 days
Secondary	Percentage of time of glucose levels above 10.0 mmol/L		6 days
Secondary	Percentage of time of glucose levels above 14.0 mmol/L		6 days
Secondary	Percentage of time of glucose levels spent below 4.0 mmol/L		6 days
Secondary	Percentage of time of glucose levels spent below 3.1 mmol/L		6 days
Secondary	Area under the curve of glucose values below 4.0 mmol/L		6 days
Secondary	Area under the curve of glucose values below 3.1 mmol/L		6 days
Secondary	Number of patients with at least one hypoglycemic event below 3.1 mmol/L with or without symptoms		6 days
Secondary	Total number of hypoglycemic event below 3.1 mmol/L		6 days
Secondary	Total insulin delivery		6 days
Secondary	Total glucagon delivery		6 days
Secondary	Standard deviation of glucose levels		6 days
Secondary	Total carbohydrate intake		6 days