DIAMOND GLP1: Dulaglutide and Insulin MicrosecretiON in Type 1 Diabetes

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT03668470

Collaborator

(none)

Enrollment

Locations

Arms

24.1

Actual Duration (Months)

6.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Some patients with type 1 diabetes (T1D) can still have some remaining insulin-positive cells in the pancreas and secrete little amounts of insulin. Despite the presence of residual beta cells, the HbA1C levels remain at high levels due to functional defects of insulin secretion associated with glucotoxicity. Previous trials have indicated that treatment with a Glucagon-like peptide 1 (GLP-1 )receptor agonist in T1D with some residual beta-cell function might improve glycemic control, reduce dose of insulin and risk of hypoglycemia.

The general hypothesis of DIAMOND-GLP1 is that GLP1-R agonists will improve blood glucose

After initial screening to select insulin microsecretors and a run-in period of one month, patients will be randomized into two arms and followed in parallel for 24 weeks :

Experimental group receiving 1.5 mg Dulaglutide s.c weekly in addition to their usual insulin regimen
Control group receiving placebo s.c weekly in addition to their usual insulin regimen.

The primary endpoint is HbA1c value at 24 weeks

Condition or Disease	Intervention/Treatment	Phase
Adult Subjects With Type1Diabetes and Insulin Microsecretion	Drug: Dulaglutide Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicentric, investigator-initiated, randomized, double-blinded, therapeutic clinical trial, placebo-controlled, two arm parallel group intervention trial during 24 weeks, phase II.Multicentric, investigator-initiated, randomized, double-blinded, therapeutic clinical trial, placebo-controlled, two arm parallel group intervention trial during 24 weeks, phase II.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Dulaglutide and Insulin MicrosecretiON in Type 1 Diabetes : A Randomized Double-blind Placebo-controlled Trial

Actual Study Start Date :

Jan 31, 2019

Actual Primary Completion Date :

Feb 3, 2021

Actual Study Completion Date :

Feb 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dulaglutide Experimental group receiving 1.5 mg Dulaglutide subcutaneously weekly in addition to their usual insulin regimen during 24 weeks	Drug: Dulaglutide Dulaglutide 1.5mg : One injection per week during 24 weeks
Placebo Comparator: placebo Control group receiving placebo subcutaneously weekly in addition to their usual insulin regimen during 24 weeks	Drug: Placebo Placebo: one injection per week during 24 weeks

Arm

Intervention/Treatment

Experimental: Dulaglutide

Experimental group receiving 1.5 mg Dulaglutide subcutaneously weekly in addition to their usual insulin regimen during 24 weeks

Drug: Dulaglutide

Dulaglutide 1.5mg : One injection per week during 24 weeks

Placebo Comparator: placebo

Control group receiving placebo subcutaneously weekly in addition to their usual insulin regimen during 24 weeks

Drug: Placebo

Placebo: one injection per week during 24 weeks

Outcome Measures

Primary Outcome Measures

HbA1c level [after 24 weeks of treatment]
Blood level

Secondary Outcome Measures

AUC us C-peptide following a MMT [before and after 24 weeks of treatment]
Evaluation and comparison before and after 24wks of treatment with Dulaglutide vs placebo the area under curve (AUC) of ultrasensitive (us) C-peptide response from 6 values following a mixed meal test (MMT)
Glucagon levels fasting and following a MMT [before and after 24 weeks of treatment]
Evaluation and comparison before and after 24wks of treatment with Dulaglutide vs placebo AUC glucagon from 6 values on fasting and after MMT
AUC us C-peptide over AUC blood glucose levels following a MMT [before and after 24 weeks of treatment]
Evaluation and comparison the ratio of the area under curve (AUC) of us C-peptide over the glucose response following a mixed meal test (MMT) with before and after 24 weeks of treatment Dulaglutide vs placebo
Daily percent times spent with continuous glucose measurements (CGM) readings between 4 and 10mmol/l, above and below this range [the run-in period (1 month) and after 24 weeks of treatment]
Evaluation and comparison the changes in the daily percent time spent with continuous glucose measurements (CGM) readings between 4 and 10mmol/l during the run-in period (1 month) and after 24 weeks with Dulaglutide vs placebo, coefficients of variation (CV) and standard deviation values (SD) as well as the average daily risk change (ADRR) of glucose values to assess blood glucose variability.
Daily insulin doses and basal/ prandial ratio [: before and after 24weeks of treatment]
Evaluation and comparison before and after 24wks of treatment with Dulaglutide vs placebo the daily insulin doses and basal/ prandial ratio
: Body weight [before and after 24weeks of treatment]
% carbohydrates [the run-in period (1 month) and after 24 weeks of treatment]
Evaluate and compare the changes in mean carbohydrate intake during the run-in period and after 24 weeks with Dulaglutide vs placebo
Number of symptomatic hypoglycemic episodes [20 months]
Evaluation and comparison the number of symptomatic (both minor and severe) hypoglycemic episodes with Dulaglutide vs placebo during the study
Number of adverse events [20 months]
Evaluation and comparison the number of adverse events with Dulaglutide vs placebo during the study
Autoantibodies to GAD65 [: before and after 24wks of treatment]
Evaluation and comparison before and after 24wks of treatment the levels and subtypes of autoantibodies associated with T1D with and without dulaglutide
insulin doses : basal/ prandial ratio [before and after 24weeks of treatment]
the insulin basal/ prandial ratio
Autoantibodies to IA-2 [before and after 24wks of treatment]
Evaluation and comparison before and after 24wks of treatment the levels and subtypes of autoantibodies associated with T1D with and without dulaglutide
Autoantibodies to ZnT8 [before and after 24wks of treatment]
Evaluation and comparison before and after 24wks of treatment the levels and subtypes of autoantibodies associated with T1D with and without dulaglutide
coefficients of variation (CV) [the run-in period (1 month) and after 24 weeks of treatment]
coefficients of variation (CV) of daily percent times spent with continuous glucose measurements (CGM) readings between 4 and 10mmol/l, above and below this range .

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients with T1D> 4years, with age range 20-60years
Diabetes onset after the age of 15years
Duration of diabetes <15 years
Treated with continuous sub-cutaneous insulin infusions (CSI) or multiple daily injections of insulin (MDI)
Measuring their blood sugar at least four times daily
Glycated hemoglobin (HbA1C) at screening >7 and <10%
16.0 kg/m2 <BMI<30.0kg/m2
Patients with childbearing potential should use effective contraception, defined as methods with a failure rate ≤ 2 % per year (OMS 2011) during the study.
Patients who gave its written informed consent to participate to the study
Patients affiliated to a social insurance regime

Randomization criteria:

Patients with fasting ultra-sensitive (us) C-peptide above 15pmol/l

Exclusion Criteria:

Patients are not eligible for this study if any of the following exclusion criteria apply:
Patients with type 2 diabetes (T2D)
Hypersensitivity to dulaglutide and/or any of its excipients
Subjects with history of severe hypoglycemia or recent (< 6 months) history of diabetic ketoacidosis
History of gastrointestinal disease with prolonged (> 3 months) nausea or vomiting, liver or kidney diseases, pancreatitis, thyroid medullary cancer or familial history of multiple endocrine neoplasia type 2
Estimated glomerular filtration rate<60ml/min/ 1.73m2 (CKD-EPI method)
Congestive heart failure
Any uncontrolled disease, cancers essentially
Chronic use of paracetamol containing products, which may falsely raise sensor glucose readings
Use of tricyclic antidepressant, selective serotonin reuptake inhibitor, triptans, neuroleptic drugs and glucocorticoid.
Patient who participated in another clinical trial on experimental drug in the previous 30 days
Patients of childbearing potential who are not using adequate contraception; Female patients who are pregnant or lactating.
Gastric bypass surgery
Patients under guardianship

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Service d'Endocrinologie, Maladies Métaboliques et Nutrition, CHU Grenoble, Hopital de la Tronche	La Tronche	France	38700
2	Département d''Endocrinologie, Diabétologie, Nutrition ; CHU Montpellier ; Hôpital Lapeyronie, Avenue du Doyen Giraud	Montpellier 5	France	34295
3	Service d'Endocrinologie, Maladies Métaboliques et Nutrition,CHU Nantes,Hôpital Nord Laennec,Bd Jacques-Monod,Saint-Herblain	NANTES cedex 1	France	44093
4	Service de Diabétologie et Maladies Métaboliques, Assistance Publique des Hôpitaux de Paris ;Hôpital Cochin, 27 rue du Faubourg Saint-Jacques	Paris	France	75014
5	Service d'Endocrinologie, Diabétologie, Maladies de la Nutrition, Hospices Civils de Lyon, Centre hospitalier Lyon-Sud	Pierre-Bénite	France	69495
6	Service de Diabétologie Maladies Métaboliques et Nutrition ; CHU Toulouse, Pôle cardiovasculaire et métabolique, Hôpital Rangueil ; 1, avenue du Professeur Jean Poulhès - TSA 50032	TOULOUSE cedex 9	France	31059
7	Service de Diabétologie, Maladies Métaboliques, Nutrition ; CHU Nancy ; Technopôle Nancy-Brabois ; Rue du Morvan,	Vandœuvre-lès-Nancy	France	54500