Ta strona została przetłumaczona automatycznie i dokładność tłumaczenia nie jest gwarantowana. Proszę odnieść się do angielska wersja za tekst źródłowy.

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

13 lutego 2020 zaktualizowane przez: 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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

28

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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.).

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Zadanie krzyżowe
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Aktywny komparator: 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)
Inny: 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.
Eksperymentalny: 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
Inny: 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.
Eksperymentalny: 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
Inny: 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.

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Ramy czasowe
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.
Ramy czasowe: 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.
Ramy czasowe: Up to 24 hours
Up to 24 hours

Miary wyników drugorzędnych

Miara wyniku
Ramy czasowe
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.
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: Up to 24 hours
Up to 24 hours
Standard deviation of glucose levels as a measure of glucose variability.
Ramy czasowe: Up to 24 hours
Up to 24 hours
Total insulin delivery.
Ramy czasowe: Up to 24 hours
Up to 24 hours
Total pramlintide delivery.
Ramy czasowe: Up to 24 hours
Up to 24 hours
Mean plasma glucose level during: a. the overall study period; b. overnight period.
Ramy czasowe: Up to 24 hours
Up to 24 hours
Mean plasma insulin concentration.
Ramy czasowe: Up to 24 hours
Up to 24 hours
Mean plasma glucagon concentration.
Ramy czasowe: Up to 24 hours
Up to 24 hours
Mean plasma amylin concentration.
Ramy czasowe: 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.
Ramy czasowe: 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.
Ramy czasowe: Up to 24 hours
Up to 24 hours

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

McGill University

Współpracownicy

Juvenile Diabetes Research Foundation

Śledczy

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

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

13 stycznia 2017

Zakończenie podstawowe (Rzeczywisty)

8 lipca 2018

Ukończenie studiów (Rzeczywisty)

8 lipca 2018

Daty rejestracji na studia

Pierwszy przesłany

22 czerwca 2016

Pierwszy przesłany, który spełnia kryteria kontroli jakości

22 czerwca 2016

Pierwszy wysłany (Oszacować)

27 czerwca 2016

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

17 lutego 2020

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

13 lutego 2020

Ostatnia weryfikacja

1 lutego 2020

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • MAP-1

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

Subskrybuj