Adult Subjects With Type1Diabetes and Insulin Microsecretion
Conditions
Keywords
type 1 diabetes, insulin microsecretion, dulaglutide, randomized, double-blind placebo-controlled trial
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
Interventions
DRUGDulaglutide
Dulaglutide 1.5mg : One injection per week during 24 weeks
DRUGPlacebo
Placebo: one injection per week during 24 weeks
Sponsors
Hospices Civils de Lyon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c level | after 24 weeks of treatment | Blood level |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
| 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 . |
| 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 |
Countries
France
Outcome results
None listed