Evaluation of Domperidone on Glycemic Control in Asymptomatic Type 1 Diabetic Patients with Delayed Gastric Emptying
- Trial ID
- 2024-514838-20-00
- Protocol
- 2021/0380/HP
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the impact of **prokinetic** treatment of gastric emptying versus placebo on glycemic control, as defined by Continuous Glucose Monitoring (CGM) criteria, in type 1 diabetic patients with delayed gastric emptying who are digestively asymptomatic and have insufficient glycemic control. This is clinically relevant as it aims to improve glycemic management in this specific patient population, potentially reducing the risk of diabetes-related complications.
Secondary objectives include:
- Determining the effect of **domperidone** on all glycemic control criteria.
- Comparing clinical and paraclinical determinants and glycemic parameters related to delayed gastric emptying between randomized and non-randomized patients.
- Evaluating the tolerability of the study treatment.
- Assessing patient compliance with the study treatment.
- Comparing the percentages of patients achieving a mean 14-day Time in Range (T.I.R.) of 70-180 mg/dL greater than 70% between the two groups.
Participants
The clinical trial involves **Type 1 diabetic patients** with delayed gastric emptying who are digestively asymptomatic and have insufficient glycemic control. The study population includes both male and female participants aged 18 to 74 years. Participants are required to have been diagnosed with Type 1 diabetes for more than five years and must be treated with a multi-injection insulin regimen or insulin pump, along with a continuous interstitial glucose recording device. The trial focuses on individuals with a glycemic target TIR (70-180 mg/dL) of less than 60% and/or a coefficient of variation (CV) greater than 40%, or those experiencing early postprandial hypoglycemia or at least three predictive pump stops in the postprandial period. Participants should have few symptoms of gastroparesis, as indicated by a GCSI score of 2 or less. The trial includes both male and female subjects, with specific considerations for women of childbearing potential, who must use effective contraception and have a negative pregnancy test at inclusion. The sponsor has not provided information on the total number of participants. The trial population was selected based on these criteria, ensuring a focus on individuals with specific glycemic control challenges and minimal gastroparesis symptoms.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **domperidone**, a prokinetic agent, on glycemic control in type 1 diabetic patients with delayed gastric emptying. This study is a randomized, double-blind, placebo-controlled trial. The trial is expected to commence on September 1, 2024, and conclude by February 1, 2028. Participants will be randomly assigned to receive either domperidone or a placebo, with the primary endpoint being the difference in the percentage of time spent within the target glycemic range (70-180 mg/dL) over a 14-day period.
The study will include several visits, beginning with a screening visit to assess eligibility based on criteria such as age, diabetes duration, and glycemic control parameters. Eligible participants will then proceed to the baseline visit, where they will be randomized and receive their assigned treatment. Follow-up visits will occur at regular intervals to monitor safety, adherence, and efficacy outcomes, including HbA1c levels, plasma fructosamine, and the number of hypoglycemic episodes. The end-of-study visit will involve a comprehensive assessment of all study parameters and the collection of any remaining study medication.
Participant involvement is expected to last for a maximum of 31 days, corresponding to the treatment period. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with study procedures, or withdrawal of consent. The trial aims to provide valuable insights into the management of glycemic control in type 1 diabetic patients with gastroparesis, potentially informing future therapeutic strategies.
Treatment
The clinical trial involves the administration of **DOMPERIDONE ARROW 10 mg**, a **film-coated tablet** containing the active substance **domperidone**. This medication is utilized as a prokinetic agent to evaluate its efficacy on glycemic control in type 1 diabetic patients with delayed gastric emptying. The pharmaceutical form is a film-coated tablet, and the route of administration is **oral**. The maximum daily dose is 30 mg, with a total maximum dose of 930 mg over a treatment period of up to 31 days. The medication is manufactured by Arrow Generiques and is authorized under the marketing authorization number NL 27475 in France. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.
The study also includes the use of a **placebo** control, identified as **Comprimés placebo à usage thérapeutique 260 mg**. The placebo is administered in a similar pharmaceutical form and route as the experimental medication to maintain blinding and ensure the validity of the trial results. The placebo serves as a comparator to assess the true efficacy of domperidone in the study population. Participants will receive either the active treatment or placebo according to the randomization schedule, and compliance will be monitored to ensure accurate data collection and analysis.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the impact of **domperidone**, a prokinetic agent, on glycemic control in type 1 diabetic patients with delayed gastric emptying. The primary endpoint is the difference in the percentage of time spent within the target glycemic range (TIR) of 70-180 mg/dL, recorded over 14 days, under treatment with domperidone or placebo. This will be measured using Continuous Glucose Monitoring (CGM) criteria.
Secondary endpoints include variations in glycemic control criteria between domperidone and placebo, such as HbA1c and plasma fructosamine assays, the number of hypoglycemic episodes, the percentage of time spent in hypoglycemia (<70 mg/dL) and hyperglycemia (>180 mg/dL), and the coefficient of glycemic variability. Additional assessments will include insulin dose, pre- and post-treatment gastric emptying data (Tlag, T1/2), and clinical and paraclinical data in each group of patients. The trial will also monitor the number of adverse events (AE) and serious adverse events (SAE), as well as the number of times treatment or placebo is taken, calculated from the number of capsules returned by the patient.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female ≥ 18 years and <75 years
- 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
- 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
- Patient with few symptoms of gastroparesis based on GCSI score ≤ 2
- Person who has read and understood the information letter and signed the consent form
- Person affiliated to a social security scheme
- 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
- Surgically sterile women (hysterectomy, bilateral salpingectomy and bilateral oophorectomy)
- 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
- Type 2 diabetic patients
- 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
- 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
- history of bariatric surgery
- Patients with CGM<70%
- Type 1 diabetic patients with glycemic target TIR (70-180 mg/dL) < 20%
- 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
- Contraindication to gastric emptying test : - allergy to eggs, gluten, milk proteins, etc. - hepatic insufficiency - pulmonary diffusion disorders
- Contraindication to placebo (calcium content): hypercalcemia/hypercalciuria, known calcium lithiasis
- Pregnant, parturient or breast-feeding women, or those without proven effective contraception
- 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
- Person deprived of liberty by an administrative or judicial decision, or person under court protection, sub-guardianship or guardianship
- patients with severe eating disorders
- Patients receiving GLP-1 analog treatment
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 01 Sept 2024 | 270 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Comprimés placebo à usage thérapeutique 260 mg | Placebo | N/A | — | — | — | N/A |
DOMPÉRIDONE ARROW 10 mg, comprimé pelliculé | Test | COMPRIMÉ PELLICULÉ | ORAL | 30 | 31 | PRD1760806 |