DOMPERIDONE for Type 1 diabetes

Inclusion criteria

• {"criterion_text":"- Male or female ≥ 18 years and <75 years"}
• {"criterion_text":"- Known type 1 diabetic patients for > 5 years treated with multi-injection insulin regimen or insulin pump with continuous interstitial glucose recording device (CGM) or closed loop"}
• {"criterion_text":"- Type 1 diabetic patients with glycemic target TIR (70-180 mg/dL) < 60% and/or CV > 40% and/or early postprandial hypoglycemia, or at least 3 predictive pump stops in the postprandial period"}
• {"criterion_text":"- Patient with few symptoms of gastroparesis based on GCSI score ≤ 2"}
• {"criterion_text":"- Person who has read and understood the information letter and signed the consent form"}
• {"criterion_text":"- Person affiliated to a social security scheme"}
• {"criterion_text":"- A woman of childbearing potential (a woman is considered to be of childbearing potential fertile, after menarche and until she reaches menopause, unless she has reached the menopausal, unless she is definitively sterile) with at least effective contraception (i.e. at least: oral progestin-only hormonal contraception for which ovulation inhibition is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide). for at least 1 month and a negative urine B-HCG pregnancy test at inclusion"}
• {"criterion_text":"- Surgically sterile women (hysterectomy, bilateral salpingectomy and bilateral oophorectomy)"}
• {"criterion_text":"- Menopausal women: The postmenopausal state is defined as the absence of menstrual periods for 12 months without any other medical cause. An elevated follicle-stimulating hormone (FSH) level in the post-menopausal interval can be used to confirm a post-menopausal state in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months' amenorrhea, a single FSH measurement is insufficient"}

Exclusion criteria

• {"criterion_text":"- Type 2 diabetic patients"}
• {"criterion_text":"- Pregnant, parturient or breast-feeding women, or those without proven effective contraception"}
• {"criterion_text":"- Patients with contraindications to DOMPERIDONE ARROW 10 mg film-coated tablet: o Hypersensitivity to the active substance or to one of the excipients o Pituitary prolactin tumor (prolactinoma) o Underlying heart disease such as congestive heart failure (NYHA stage ≥2), o Kalemia less than 3.7 mmol/L or greater than 5.5 mmol/L, o Magnesemia less than 0.7 mmol/L o Hepatic impairment (TGO, TGP, GGT>2N, TP<70% (unless on anticoagulant)) o Known prolongation of cardiac conduction intervals, notably the QTc interval (QTc greater than 440 ms for men and greater than 460 ms for women) o Use of drugs that prolong the QTc interval (class IA antiarrhythmics (e.g. disopyramide, hydroquinidine, quinidine) and class III antiarrhythmics (e.g. amiodarone, dofetilide, dronedarone, ibutilide, sotalol), certain antipsychotics (e.g. haloperidol, pimozide, sertindole), certain antidepressants (e.g. citalopram, escitalopram), certain antibiotics (e.g. erythromycin, levifloxacin, moxifloxacin, spiramycin), certain antifungals (e.g. pentamidine, fluconazole), certain antimalarial drugs (in particular halofantrine, lumefantrine), certain digestive drugs (e.g. cisapride, dolasetron, prucalopride), certain antihistamines (e.g. mequitazine, mizolastine), certain anticancer drugs (e.g. toremifene, vandetanib, vincamine), certain other drugs (e.g. bepridil, diphemanil, methadone), apomorphine (unless the benefit of concomitant administration outweighs the risks, and only if the precautions recommended for concomitant administration are strictly observed). o Taking levodopa o Use of drugs that are potent or moderate inhibitors of CYP3A4: antiproteases, systemic azole antifungals, certain macrolide antibiotics (clarithromycin, telithromycin, azithromycin, roxithromycin, etc.), diltiazem, verapamil, etc. o Bradycardia (< 50 bpm) o Use of medication that induces bradycardia and hypokalemia o Presence of gastrointestinal bleeding, mechanical obstruction or perforation o Lactose contraindication: galactose intolerance, total lactase deficiency, glucose-galactose malabsorption syndrome o Confirmed or suspected pheochromocytoma due to the risk of severe episodes of hypertension"}
• {"criterion_text":"- Person deprived of liberty by an administrative or judicial decision, or person under court protection, sub-guardianship or guardianship"}
• {"criterion_text":"- patients with severe eating disorders"}
• {"criterion_text":"- Patients receiving GLP-1 analog treatment"}
• {"criterion_text":"- Person taking part in another trial / having taken part in another therapeutic trial (study involving a drug or medical device) which could interfere with the products or procedures being investigated within a period of 4 weeks prior to inclusion"}
• {"criterion_text":"- Any history of illness or psychological or sensory abnormality likely to prevent the subject from fully understanding the conditions required for participation in the protocol or from giving informed consent"}
• {"criterion_text":"- history of bariatric surgery"}
• {"criterion_text":"- Patients with CGM<70%"}
• {"criterion_text":"- Type 1 diabetic patients with glycemic target TIR (70-180 mg/dL) < 20%"}
• {"criterion_text":"- Patients with renal insufficiency (GFR<60 ml/min according to CKD-EPI formula), - Patients with contraindications to DOMPERIDONE ARROW 10 mg film-coated tablet: o Hypersensitivity to the active substance or to one of the excipients o Pituitary prolactin tumor (prolactinoma) o Underlying heart disease such as congestive heart failure (NYHA stage ≥2), o Kalemia less than 3.7 mmol/L or greater than 5.5 mmol/L, o Magnesemia less than 0.7 mmol/L o Hepatic impairment (TGO, TGP, GGT>2N, TP<70% (unless on anticoagulant)) o Known prolongation of cardiac conduction intervals, notably the QTc interval (QTc greater than 440 ms for men and greater than 460 ms for women) o Use of drugs that prolong the QTc interval (class IA antiarrhythmics (e.g. disopyramide, hydroquinidine, quinidine) and class III antiarrhythmics (e.g. amiodarone, dofetilide, dronedarone, ibutilide, sotalol), certain antipsychotics (e.g. haloperidol, pimozide, sertindole), certain antidepressants (e.g. citalopram, escitalopram), certain antibiotics (e.g. erythromycin, levifloxacin, moxifloxacin, spiramycin), certain antifungals (e.g. pentamidine, fluconazole), certain antimalarial drugs (in particular halofantrine, lumefantrine), certain digestive drugs (e.g. cisapride, dolasetron, prucalopride), certain antihistamines (e.g. mequitazine, mizolastine), certain anticancer drugs (e.g. toremifene, vandetanib, vincamine), certain other drugs (e.g. bepridil, diphemanil, methadone), apomorphine (unless the benefit of concomitant administration outweighs the risks, and only if the precautions recommended for concomitant administration are strictly observed). o Taking levodopa o Use of drugs that are potent or moderate inhibitors of CYP3A4: antiproteases, systemic azole antifungals, certain macrolide antibiotics (clarithromycin, telithromycin, azithromycin, roxithromycin, etc.), diltiazem, verapamil, etc. o Bradycardia (< 50 bpm) o Use of medication that induces bradycardia and hypokalemia o Presence of gastrointestinal bleeding, mechanical obstruction or digestive perforation o Lactose contraindication: galactose intolerance, total lactase deficiency, glucose-galactose malabsorption syndrome"}
• {"criterion_text":"- Contraindication to gastric emptying test : \t\t- allergy to eggs, gluten, milk proteins, etc. \t\t- hepatic insufficiency \t- pulmonary diffusion disorders"}
• {"criterion_text":"- Contraindication to placebo (calcium content): hypercalcemia/hypercalciuria, known calcium lithiasis"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint of this study is the difference of percentages of time spent within the TIR glycemic target range (70-180 mg/dL) recorded over 14 days under prokinetic treatment (domperidone) or placebo in T1D patients with gastroparesis and inadequate glycemic control","definition_or_measurement_approach":"Difference in percentage of time-in-range (70-180 mg/dL) recorded over 14 days using Continuous Glucose Monitoring (CGM)"}

Secondary endpoints

• {"endpoint_text":"- Variation in glycemic control criteria between domperidone and placebo (measurement of differences) o HbA1c assay o Plasma fructosamine assay, o number of hypoglycemic episodes, including severe ones, o percentage of time spent in hypoglycemia (<70mg/dL), o percentage of time spent in hyperglycemia (>180mg/dL), o coefficient of glycemic variability, o GMI o TIR, TBR, TAR, CV for each meal; o Insulin dose o Pre- and post-treatment gastric emptying data Tlag, T1/2","definition_or_measurement_approach":"Measured by laboratory assays (HbA1c, plasma fructosamine), CGM-derived metrics (TIR, TBR, TAR, CV, GMI), counts of hypoglycemic episodes (including severe), insulin dose records, and gastric emptying parameters (Tlag, T1/2) pre- and post-treatment"}
• {"endpoint_text":"- Clinical and paraclinical data in each group of T1D patients with or without delayed gastric emptying such as: -Age,sex,duration of diabetes,... -Total insulin dose,treatment modalities -Complications of diabetes: retinopathy,neuropathy,nephropathy,history of foot ulcers,vascular atheroma;cardiac,PAOD -VX neck,HbA1c,fructosamine,nb of hypoglycemic episodes,TIR,TBR,TAR,CV(overall & for each meal);GMI,GRI,blood glucose at start of emptying, 3-day weekly analysis, GCSI score","definition_or_measurement_approach":"Collection of demographic, clinical history, diabetes complications, laboratory measures (HbA1c, fructosamine), CGM-derived metrics, gastric emptying test results and symptom scores (GCSI)"}
• {"endpoint_text":"- Number of AE and SAE","definition_or_measurement_approach":"Adverse events and serious adverse events recorded per standard safety reporting"}
• {"endpoint_text":"- Number of times treatment/placebo taken (calculated from number of capsules returned by patient)","definition_or_measurement_approach":"Adherence measured by returned capsule/tablet counts"}
• {"endpoint_text":"- Ratio of time spent in target range (70-180 mg/dl) over 14 days per subject (in hours)","definition_or_measurement_approach":"CGM-derived total hours spent in 70-180 mg/dL over 14 days per subject"}

France

Earliest CTIS Part Ii Submission Date

27-08-2024

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

538

Number Of Sites

8

Number Of Participants

270

Primary sponsor

Full Name

Centre Hospitalier Universitaire Rouen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France