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Effect of Basal-Bolus Closed-Loop Co-Administration of Insulin and Pramlintide on Improving the Glycemic Control in Type 1 Diabetes

13 februari 2020 bijgewerkt door: Ahmad Haidar, McGill University

A Randomized, Three-way, Crossover Study to Assess the Efficacy of Fast-acting Insulin-plus-pramlintide Closed-loop Co-administration, Regular Insulin-plus-pramlintide Closed-loop Co-administration, and Fast-acting Insulin-alone Closed-loop Infusion in Regulating Glucose Levels Over a 24-hour Period in Adults With Type 1 Diabetes in Inpatient Settings.

The closed-loop delivery system is composed of an insulin pump, a continuous glucose sensor and a dosing algorithm that calculates the insulin dose to infuse based on sensor readings. Pramlintide is a drug and an analog of amylin, a hormone that is co-secreted with insulin in healthy individuals, and is deficient in people with type 1 diabetes. Co-injection of pramlintide with insulin at meal times improves glucose control in type 1 diabetes. Literature data suggests that regular insulin may better match the effect of pramlintide compared to rapid insulin in regulating post-prandial glucose levels.

The purpose of this study is to compare the effectiveness of 3 strategies to control your day-and-night glucose levels:

  1. rapid insulin-alone closed-loop delivery;
  2. rapid insulin-plus-pramlintide closed-loop delivery;
  3. regular insulin-plus-pramlintide closed-loop delivery.

The primary hypotheses are:

  1. During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and fast-acting insulin improves glucose control compared to fast-acting insulin-alone infusion.
  2. During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and regular insulin improves glucose control compared to fast-acting insulin-alone infusion.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

The closed-loop delivery system is composed of an insulin pump, a continuous glucose sensor and a dosing algorithm that calculates the insulin dose to infuse based on sensor readings. Pramlintide is a drug and an analog of amylin, a hormone that is co-secreted with insulin in healthy individuals, and is deficient in people with type 1 diabetes. Co-injection of pramlintide with insulin at meal times improves glucose control in type 1 diabetes.

Literature data suggests that the pharmacodynamics of regular insulin may better match the effect of pramlintide compared to the pharmacodynamics of fast-acting insulin. Moreover, the cost of regular insulin is significantly lower than fast-acting insulin. Therefore, if a similar (or better) glucose profile can be achieved with regular insulin-plus-pramlintide compared to fast-acting insulin-plus-pramlintide, then a co-formulation employing regular insulin should be prioritized.

Therefore, in this protocol, we aim to assess the effect of the simultaneous, closed-loop, basal-bolus infusion of pramlintide with insulin at a fixed ratio in controlling glucose levels. In the first experimental arm, we propose to infuse pramlintide with fast-acting insulin. In the second experimental arm, pramlintide will be infused with regular insulin. The control arm will be fast-acting insulin-alone closed-loop system.

The aim of the study is to assess the efficacy of the simultaneous, closed-loop, basal-bolus infusion of pramlintide with fast-acting insulin at a fixed ratio and pramlintide with regular insulin at a fixed ratio in controlling glucose levels compared to fast-acting insulin-alone closed-loop infusion.

The investigators aim to conduct a randomized, three-way, crossover trial to compare the efficacy of 1) fast-acting insulin-plus-pramlintide closed-loop delivery, 2) regular insulin-plus-pramlintide closed-loop delivery, and 3) fast-acting insulin-alone closed-loop delivery in regulating glucose levels over a period of 24 hours in a study on adults in inpatient settings. Insulin (fast-acting and regular) and pramlintide are given with fixed ratio (6 µg of pramlintide for each unit of insulin).

Before each 24-hour intervention visit, the participant's insulin therapy (basal rates and insulin-to-carbohydrate ratios) will be optimized for a minimum of 10 days, with a target of 14 days.

There will be a wash-out period of 0 to 42 days between the three intervention arms (termination of 24-hr intervention and start of next optimization period).

The primary hypotheses are:

  1. During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and fast-acting insulin improves glucose control compared to fast-acting insulin-alone infusion.
  2. During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and regular insulin improves glucose control compared to fast-acting insulin-alone infusion.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

28

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Canada
    • Quebec
      • Montréal, Quebec, Canada
        • McGill University Health Centre

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Males and females ≥ 18 years of age.
  • Clinical diagnosis of type 1 diabetes for at least 12 months. (The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.)
  • The subject will have been on insulin pump therapy for at least 6 months.
  • HbA1c ≤ 10%.

Exclusion Criteria:

  • Current or ≤ 1 month use of other antihyperglycemic agents (SGLT2, GLP-1, Metformin, Acarbose, etc.…).
  • Severe hypoglycemic episode within one month of screening.
  • Severe diabetes keto-acidosis episode within one month of screening.
  • Planned or ongoing pregnancy.
  • Known or suspected allergy to the study drugs.
  • Gastroparesis.
  • Use of prokinetic drugs that stimulate gastric emptying (domperidone, cisapride, metoclopramide).
  • Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator.
  • Recent (< 6 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
  • Current use of glucocorticoid medication.
  • Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
  • Failure to comply with team's recommendations (e.g. not willing to eat meals/snacks, not willing to change pump parameters, etc.).

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Crossover-opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: Rapid Insulin-alone closed-loop delivery
Rapid Insulin will be delivered by subcutaneous infusion. Interventions: 24-hour inpatient intervention Drug: Rapid acting Insulin (aspart, lispro, glulisine)
Ander: 24-hour inpatient intervention
Subjects will be admitted at the research facility at 7:30. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. Each 24-hour intervention visit includes 3 standardized meals (8:00, 12:00, and 17:00), an evening snack (21:00) and an overnight stay. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The insulin and pramlintide pumps' infusion rates will then be changed manually based on the computer generated recommendation, while still maintaining the ratio. The computer generated recommendations are based on a predictive algorithm.
Experimenteel: Rapid Insulin-plus-pramlintide closed-loop delivery

Rapid insulin and pramlintide will be delivered by subcutaneous infusion using a fixed ratio (6 µg pramlintide/unit insulin).

Interventions: 24-hour inpatient intervention Drug: Rapid acting Insulin (aspart, lispro, glulisine) Drug: Pramlintide
Ander: 24-hour inpatient intervention
Subjects will be admitted at the research facility at 7:30. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. Each 24-hour intervention visit includes 3 standardized meals (8:00, 12:00, and 17:00), an evening snack (21:00) and an overnight stay. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The insulin and pramlintide pumps' infusion rates will then be changed manually based on the computer generated recommendation, while still maintaining the ratio. The computer generated recommendations are based on a predictive algorithm.
Experimenteel: Regular Insulin-plus-pramlintide closed-loop delivery

Regular insulin and pramlintide will be delivered by subcutaneous infusion using a fixed ratio (6 µg pramlintide/unit insulin).

Interventions: 24-hour inpatient intervention Drug: Regular Insulin (humulin R) Drug: Pramlintide
Ander: 24-hour inpatient intervention
Subjects will be admitted at the research facility at 7:30. A cannula will be inserted into an arm or a hand vein for blood sampling purposes. Each 24-hour intervention visit includes 3 standardized meals (8:00, 12:00, and 17:00), an evening snack (21:00) and an overnight stay. The glucose level as measured by the real time sensor will be entered manually into the computer every 10 minutes. The insulin and pramlintide pumps' infusion rates will then be changed manually based on the computer generated recommendation, while still maintaining the ratio. The computer generated recommendations are based on a predictive algorithm.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Percentage of time of plasma glucose levels spent in target range. Target range is defined to be between 3.9 and 10.0 mmol/L of fast-acting insulin-plus-pramlintide closed-loop delivery vs. fast-acting insulin-alone closed-loop delivery.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Percentage of time of plasma glucose levels spent in target range. Target range is defined to be between 3.9 and 10.0 mmol/L of regular insulin-plus-pramlintide closed-loop delivery vs. fast-acting insulin-alone closed-loop delivery.
Tijdsspanne: Up to 24 hours
Up to 24 hours

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Percentage of time of plasma glucose levels spent in target range, comparing fast-acting insulin-plus-pramlintide closed-loop delivery vs. regular insulin-plus-pramlintide closed-loop delivery.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Percentage of time (8:00-8:00) of plasma glucose levels spent: a. 3.9-7.8 mmol/L; b. 3.9-10 mmol/L; c. <3.9 mmol/L; d. <3.3 mmol/L; e. <2.8 mmol/L; f. >7.8 mmol/L; g. >10 mmol/L; h. >13.9 mmol/L; i. >16.7 mmol/L
Tijdsspanne: Up to 24 hours
Up to 24 hours
Percentage of overnight time (23:00-8:00) of plasma glucose levels: a. 3.9-7.8 mmol/L; b. 3.9-10 mmol/L; c. <3.9 mmol/L; d. <3.3 mmol/L; e. <2.8 mmol/L; f. >7.8 mmol/L; g. >10 mmol/L; h. >13.9 mmol/L; i. >16.7 mmol/L
Tijdsspanne: Up to 24 hours
Up to 24 hours
Standard deviation of glucose levels as a measure of glucose variability.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Total insulin delivery.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Total pramlintide delivery.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Mean plasma glucose level during: a. the overall study period; b. overnight period.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Mean plasma insulin concentration.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Mean plasma glucagon concentration.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Mean plasma amylin concentration.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Number of subjects experiencing hypoglycemia requiring oral treatment during: a. the overall study period; b. the night.
Tijdsspanne: Up to 24 hours
Up to 24 hours
Gastrointestinal symptoms during the treatment optimization (i.e., the minimum 10 days prior to the 24-hour closed-loop visits) and during the 24-hour closed-loop visits.
Tijdsspanne: Up to 24 hours
Up to 24 hours

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

McGill University

Medewerkers

Juvenile Diabetes Research Foundation

Onderzoekers

  • Hoofdonderzoeker: Ahmad Haidar, McGill University
  • Hoofdonderzoeker: Laurent Legault, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

13 januari 2017

Primaire voltooiing (Werkelijk)

8 juli 2018

Studie voltooiing (Werkelijk)

8 juli 2018

Studieregistratiedata

Eerst ingediend

22 juni 2016

Eerst ingediend dat voldeed aan de QC-criteria

22 juni 2016

Eerst geplaatst (Schatting)

27 juni 2016

Updates van studierecords

Laatste update geplaatst (Werkelijk)

17 februari 2020

Laatste update ingediend die voldeed aan QC-criteria

13 februari 2020

Laatst geverifieerd

1 februari 2020

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • MAP-1

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

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