NCT03682640

Azithromycin Insulin Diet Intervention Trial in Type 1 Diabetes

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Uppsala University · Academic / Other
• Sex: All
• Age: 72 Months – 192 Months
• Healthy volunteers: Not accepted

Summary

Increasing evidences suggest that infections are important etiological factors for the development of Type 1 Diabetes (T1D). The overall hypothesis of the study is that the treatment of children, during the first year after diagnosis of T1D with Azithromycin, combined with repeated episodes of intensified insulin treatment to induce maximal beta-cell rest, and dietician support to promote dietary habits that minimize the likelihood of bacterial reflux from the duodenum to the pancreatic duct, will lead to preservation of beta cell function. This trial will examine whether the AIDIT protocol initiated within one week from diagnosis could preserve insulin production in children with Type 1 Diabetes.

Detailed description

The study is a 2-arm, randomized, open, single center, clinical trial. Eligible patients with type 1 diabetes will be randomized to the AIDIT protocol or treatment as usual (TAU). All patients diagnosed with T1D and included in the study will receive standard of care. In addition, the AIDIT protocol will include 1) treatment with Azithromycin for 52 weeks using a protocol for children with cystic fibrosis, 2) repeated treatments with intensified supervised high dose insulin infusion, and 3) extra advice and support from the study dietician. 1. Azithromycin Azithromycin will be administered orally. Azithromycin will be given three times per week for 52 weeks. The dose will be 500 mg for children with body weight ≥ 30 kg and 250 mg if body weight \< 30 kg. 2. Intensified supervised high dose insulin infusions Participants will, in addition to Azithromycin, also be subjected to intensified anti-diabetic treatment to achieve increased beta-cell rest. This will be achieved by insulin lispro given as a supervised iv infusion for 72 hours within one week of diagnosis and by subcutaneous infusion 6-8 hours during one day in study week 5, 9, 13, 17 (±1 week) and 25, 34, 43 (±2 weeks) after inclusion. The intensified treatments will aim to target a blood glucose level of 4.0 ± 0.5 mmol/l. The efficacy of the intended maximal beta cell rest will be evaluated by measurement of plasma glucose and endogenous C-peptide. If C-peptide remains positive during the supervised infusion of insulin lispro this will be interpreted as that the insulin dose needs to be increased at the next treatment occasion to achieve beta-cell rest. 3. Dietician support Participants will receive extra advice and support from the study dietician within the first week after randomization, and after 7 and 17 weeks. Personalized nutritional advice on intake of carbohydrates, fat and protein based on four-day food records will be given to in order to reduce insulin resistance and insulin need in accordance with ISPAD guidelines. By giving nutritional advices on less volume of the meals, especially of the fluid (maximum 300 ml per meal), and by trying to extend the meal time to at least 20 minutes, the reflux into ductus pancreaticus might be reduced. All patients will be offered an examination of their pancreas with MRI at 0 and 12 months after inclusion. In addition, plasma samples taken at inclusion and after 1.5 and 12 months will be analysed for the presence of cell-free DNA indicating ongoing cell destruction. Cell-specific methylation patterns of this cell-free DNA will be analysed to determine cell-type specific cell death. The effect of the addition of treatment according to the AIDIT protocol will be evaluated with a Mixed Meal Tolerance Test (MMTT) to explore the effect on preservation of beta-cell function.

Conditions

• Diabetes Mellitus, Type 1
• Diabetes Mellitus
• Metabolic Disease
• Glucose Metabolism Disorders
• Endocrine System Diseases
• Juvenile Diabetes
• Insulin Dependent Diabetes
• Type 1 Diabetes Mellitus
• Inflammation
• Diet Modification

Interventions

Type	Name	Description
DRUG	Azithromycin Monohydrate	Azithromycin Monohydrate tablet (Azithromycin Sandoz) or oral suspension (Azithromax).
DRUG	Insulin Lispro	Solution for intravenous or subcutaneous use
BEHAVIORAL	Dietician support	Dietary advice

Timeline

• Start date: 2018-09-01
• Primary completion: 2021-12-31
• Completion: 2021-12-31
• First posted: 2018-09-24
• Last updated: 2018-09-24

Locations

1 site across 1 country: Sweden