A Phase I/II Trial to Preserve Residual Insulin Secretion in Children With Recent Onset Type 1 Diabetes by Giving Verapamil

Summary

The objective of this trial is first to evaluate safety and then the effect on preservation of residual beta cell function also clinical efficacy by treatment with Verapamil in children with recent onset Type 1 diabetes. Patients are included with the following inclusion criteria; * Informed consent given by patients and caregivers/parents Type 1 diabetes according to the ADA classification within the previous 3 months at the time of screening * Age 4.00 -9.99 years at Diagnosis of Type 1 diabetes * Fasting C-peptide \>0.12 nmol/ml * Elevated levels of any diabetes-related antibody/ies (eg GADA, IAA, IA-2A, ZnT8A ) is/are present. While they are not allowed to participate if they eg have previous cardiac problems or abnormal ECG. The study is a Phase I/II trial, with two parts: A. 6 patients participate in an open controlled study without any placebo with the primary aim to evaluate safety. After a baseline evaluation including ECG, physical examination, mixed Meal Tolerance Test evaluating residual beta cell fuction, these patients will be treated for 12 months with Verapamil 3-6 mg/kg body weight/24 hrs, divided into two daily doses. When these 6 patients have been followed for 6 months, and safety and tolerability is regarded as good, part B will start: In part B the next 30 patients will be randomized 1:1 in a double-blind placebo-controlled study into two arms: 15 patients will receive active treatment for 12 months with Verapamil 3-6 mg/kg body weight/24 hrs divided into two daily oral doses, while 15 patients will receive placebo in two daily doses for 12 months. Efficacy will be evaluated with MMTT and clinical response ( insulin dose/kg body weight/24 hrs, HbA1c, and CGM data on Glucose Time in Range), from baseline and after 12 and 24 months. There is a great benefit of preservation of residual insulin secretion, and therefore therapies aiming at preservation of this function justifies treatments that are quite heavy, even dangerous and expensive. In this study the investigators will use oral Verapamil, a drug which is used as antihypertensive treatment in different ages, even in children in the neonatal period, with limited adverse events and risks. Verapamil treatment has shown encouraging results preserving beta cell function in Type 1 diabetes in adults, and the investigators expect to get similar positive effects also in young children, in whom so far no immune intervention has shown efficacy.

Eligibility

Inclusion criteria: • Informed consent given by patients and caregivers/parents

* Type 1 diabetes according to the ADA classification within the previous 3 months at the time of screening
* Age 4.00 -9.99 years at Diagnosis of Type 1 diabetes
* Fasting C-peptide \>0.12 nmol/ml
* Elevated levels of any diabetes-related antibody/ies (eg GADA, IAA, IA-2A, ZnT8A ) is/are present.

Exclusion criteria: • Cardiac disease/problems, abnormal ECG, or history of abnormal blood pressure

* Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
* Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
* Treatment with any oral or injected anti-diabetic medications other than insulin
* A history of anaemia or significantly abnormal haematology results at screening
* Participation in other clinical trials with a new chemical entity within the previous 3 months
* Inability or unwillingness to comply with the provisions of this protocol
* A significant illness other than diabetes within 2 weeks prior to first dosing. However treated celiac disease and hypothyroidism with adequate treatment will be accepted.
* Deemed by the investigator not being able to follow instructions and/or follow the study protocol

Conditions2

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