- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT02814123
Effect of Basal-Bolus Closed-Loop Co-Administration of Insulin and Pramlintide on Improving the Glycemic Control in Type 1 Diabetes
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:
- rapid insulin-alone closed-loop delivery;
- rapid insulin-plus-pramlintide closed-loop delivery;
- regular insulin-plus-pramlintide closed-loop delivery.
The primary hypotheses are:
- 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.
- During closed-loop control, the simultaneous basal-bolus infusion of pramlintide and regular insulin improves glucose control compared to fast-acting insulin-alone infusion.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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:
- 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.
- 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
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
-
Quebec
-
Montréal, Quebec, Canada
- McGill University Health Centre
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.).
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Aktiv 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)
|
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.
|
Eksperimentell: 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 |
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.
|
Eksperimentell: 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 |
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.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
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.
Tidsramme: 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.
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
---|---|
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.
Tidsramme: 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
Tidsramme: 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
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Standard deviation of glucose levels as a measure of glucose variability.
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Total insulin delivery.
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Total pramlintide delivery.
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Mean plasma glucose level during: a. the overall study period; b. overnight period.
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Mean plasma insulin concentration.
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Mean plasma glucagon concentration.
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Mean plasma amylin concentration.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: Up to 24 hours
|
Up to 24 hours
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Ahmad Haidar, McGill University
- Hovedetterforsker: Laurent Legault, McGill University Health Centre/Research Institute of the McGill University Health Centre
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Haidar A, Tsoukas MA, Bernier-Twardy S, Yale JF, Rutkowski J, Bossy A, Pytka E, El Fathi A, Strauss N, Legault L. A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial. Diabetes Care. 2020 Mar;43(3):597-606. doi: 10.2337/dc19-1922. Epub 2020 Jan 23.
- Tsoukas M, Rutkowski J, El-Fathi A, Yale JF, Bernier-Twardy S, Bossy A, Pytka E, Legault L, Haidar A. Accuracy of FreeStyle Libre in Adults with Type 1 Diabetes: The Effect of Sensor Age. Diabetes Technol Ther. 2020 Mar;22(3):203-207. doi: 10.1089/dia.2019.0262. Epub 2020 Jan 23.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- MAP-1
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
Kliniske studier på Diabetes mellitus, type 1
-
University of Colorado, DenverMassachusetts General Hospital; Beta Bionics, Inc.FullførtDiabetes mellitus, type 1 | Type 1 diabetes | Diabetes type 1 | Type 1 diabetes mellitus | Autoimmun diabetes | Diabetes mellitus, insulinavhengig | Juvenil-Debut Diabetes | Diabetes, autoimmun | Insulinavhengig diabetes mellitus 1 | Diabetes mellitus, insulinavhengig, 1 | Diabetes mellitus, sprø | Diabetes mellitus... og andre forholdForente stater
-
University of California, San FranciscoJuvenile Diabetes Research FoundationFullførtType 1 diabetes mellitus | Diabetes mellitus, type I | Insulinavhengig diabetes mellitus 1 | Diabetes mellitus, insulinavhengig, 1 | IDDMForente stater, Australia
-
Capillary Biomedical, Inc.FullførtDiabetes mellitus, type 1 | Type 1 diabetes | Type 1 diabetes mellitus | Diabetes mellitus, insulinavhengig, 1Australia
-
Spiden AGDCB Research AGFullførtType 1 diabetes mellitus | Type 1 diabetes mellitus med hypoglykemi | Type 1 diabetes mellitus med hyperglykemiSveits
-
SanofiFullførtType 1 Diabetes Mellitus-Type 2 Diabetes MellitusUngarn, Den russiske føderasjonen, Tyskland, Polen, Japan, Forente stater, Finland
-
Capillary Biomedical, Inc.AvsluttetType 1 diabetes | Type 1 diabetes mellitus | Diabetes mellitus, type I | Diabetes mellitus, insulinavhengig, 1 | IDDMØsterrike
-
Instytut Diabetologii Sp. z o.o.National Center for Research and Development, Poland; Nalecz Institute...UkjentType 1 diabetes mellitus med hyperglykemi | Type 1 diabetes mellitus med hypoglykemiPolen
-
National Institute of Allergy and Infectious Diseases...PPD; Rho Federal Systems Division, Inc.; Immune Tolerance Network (ITN)FullførtType 1 diabetes mellitus | T1DM | T1D | Nyoppstått type 1 diabetes mellitusForente stater, Australia
-
AstraZenecaFullførtType 2 diabetes mellitus | Type 1 diabetes mellitusForente stater
-
Shanghai Changzheng HospitalRekrutteringSprø type 1 diabetes mellitusKina
Kliniske studier på 24-hour inpatient intervention
-
Johns Hopkins UniversityRekrutteringRyggsmerte | Smerte i korsryggenForente stater