Dulaglutide and Insulin MicrosecretiON in Type 1 Diabetes

NCT03668470 | Completed Phase 2

• 1 other identifier: 69HCL18_0047
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

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

Conditions

Adult Subjects With Type1Diabetes and Insulin Microsecretion

Keywords

type 1 diabetes; insulin microsecretion; dulaglutide; randomized; double-blind placebo-controlled trial

Outcome Measures

Primary Outcomes (1)

• HbA1c level

  Blood level

  after 24 weeks of treatment

Secondary Outcomes (14)

• AUC us C-peptide following a MMT

  before and after 24 weeks of treatment

• Glucagon levels fasting and following a MMT

  before and after 24 weeks of treatment

• AUC us C-peptide over AUC blood glucose levels following a MMT

  before and after 24 weeks of treatment

• 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

• Daily insulin doses and basal/ prandial ratio

  : before and after 24weeks of treatment

Study Arms (2)

Dulaglutide

EXPERIMENTAL

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

Drug: Dulaglutide

placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Dulaglutide DRUG

Dulaglutide 1.5mg : One injection per week during 24 weeks

Dulaglutide

Placebo DRUG

Placebo: one injection per week during 24 weeks

placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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%
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (7)

Service d'Endocrinologie, Maladies Métaboliques et Nutrition, CHU Grenoble, Hopital de la Tronche

La Tronche, 38700, France

Location

Département d''Endocrinologie, Diabétologie, Nutrition ; CHU Montpellier ; Hôpital Lapeyronie, Avenue du Doyen Giraud

Montpellier, 34295, France

Location

Service d'Endocrinologie, Maladies Métaboliques et Nutrition,CHU Nantes,Hôpital Nord Laennec,Bd Jacques-Monod,Saint-Herblain

Nantes, 44093, France

Location

Service de Diabétologie et Maladies Métaboliques, Assistance Publique des Hôpitaux de Paris ;Hôpital Cochin, 27 rue du Faubourg Saint-Jacques

Paris, 75014, France

Location

Service d'Endocrinologie, Diabétologie, Maladies de la Nutrition, Hospices Civils de Lyon, Centre hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

Service de Diabétologie Maladies Métaboliques et Nutrition ; CHU Toulouse, Pôle cardiovasculaire et métabolique, Hôpital Rangueil ; 1, avenue du Professeur Jean Poulhès - TSA 50032

Toulouse, 31059, France

Location

Service de Diabétologie, Maladies Métaboliques, Nutrition ; CHU Nancy ; Technopôle Nancy-Brabois ; Rue du Morvan,

Vandœuvre-lès-Nancy, 54500, France

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

dulaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Charles THIVOLET

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 12, 2018
• Study Start: January 31, 2019
• Primary Completion: February 3, 2021
• Study Completion: February 3, 2021
• Last Updated: July 8, 2021

Record last verified: 2021-07

Locations

FR (7)