Clinical trial NCT03668470: Dulaglutide and Insulin MicrosecretiON in Type 1 Diabetes
Official title: Dulaglutide and Insulin MicrosecretiON in Type 1 Diabetes : A Randomized Double-blind Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Subjects With Type1Diabetes and Insulin Microsecretion
Keywords: type 1 diabetes
insulin microsecretion
dulaglutide
randomized
double-blind placebo-controlled trial
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2018-09-12
Enrollment: 45
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: HbA1c level
timeFrame: after 24 weeks of treatment
Secondary outcomes:
measure: AUC us C-peptide following a MMT
timeFrame: before and after 24 weeks of treatment
measure: Glucagon levels fasting and following a MMT
timeFrame: before and after 24 weeks of treatment
measure: AUC us C-peptide over AUC blood glucose levels following a MMT
timeFrame: before and after 24 weeks of treatment
measure: Daily percent times spent with continuous glucose measurements (CGM) readings between 4 and 10mmol/l, above and below this range
timeFrame: the run-in period (1 month) and after 24 weeks of treatment
measure: Daily insulin doses and basal/ prandial ratio
timeFrame: : before and after 24weeks of treatment
measure: : Body weight
timeFrame: before and after 24weeks of treatment
measure: % carbohydrates
timeFrame: the run-in period (1 month) and after 24 weeks of treatment
measure: Number of symptomatic hypoglycemic episodes
timeFrame: 20 months
measure: Number of adverse events
timeFrame: 20 months
measure: Autoantibodies to GAD65
timeFrame: : before and after 24wks of treatment
measure: insulin doses : basal/ prandial ratio
timeFrame: before and after 24weeks of treatment
measure: Autoantibodies to IA-2
timeFrame: before and after 24wks of treatment
measure: Autoantibodies to ZnT8
timeFrame: before and after 24wks of treatment
measure: coefficients of variation (CV)
timeFrame: the run-in period (1 month) and after 24 weeks of treatment
Other outcomes:
Locations:
city: La Tronche
country: France
facility: Service d'Endocrinologie, Maladies Métaboliques et Nutrition, CHU Grenoble, Hopital de la Tronche
city: Montpellier 5
country: France
facility: Département d''Endocrinologie, Diabétologie, Nutrition ; CHU Montpellier ; Hôpital Lapeyronie, Avenue du Doyen Giraud
city: NANTES cedex 1
country: France
facility: Service d'Endocrinologie, Maladies Métaboliques et Nutrition,CHU Nantes,Hôpital Nord Laennec,Bd Jacques-Monod,Saint-Herblain
city: Paris
country: France
facility: Service de Diabétologie et Maladies Métaboliques, Assistance Publique des Hôpitaux de Paris ;Hôpital Cochin, 27 rue du Faubourg Saint-Jacques
city: Pierre-Bénite
country: France
facility: Service d'Endocrinologie, Diabétologie, Maladies de la Nutrition, Hospices Civils de Lyon, Centre hospitalier Lyon-Sud
city: TOULOUSE cedex 9
country: France
facility: Service de Diabétologie Maladies Métaboliques et Nutrition ; CHU Toulouse, Pôle cardiovasculaire et métabolique, Hôpital Rangueil ; 1, avenue du Professeur Jean Poulhès - TSA 50032
city: Vandœuvre-lès-Nancy
country: France
facility: Service de Diabétologie, Maladies Métaboliques, Nutrition ; CHU Nancy ; Technopôle Nancy-Brabois ; Rue du Morvan,
Study officials:
affiliation: Hospices Civils de Lyon
name: Charles THIVOLET
role: PRINCIPAL_INVESTIGATOR
References: