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

NCT07199946 | Recruiting Phase 1 DMC

• 2 other identifiers: 202100-30962024-515106-30-00
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Type 1 Diabetes

Keywords

c-peptide; beta cell function; children; Verapamil

Outcome Measures

Primary Outcomes (2)

• Change in C-peptide AUCmean 0-120 min) during an MMTT from baseline to month 24.

  24 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0".

  Adverse events are registered after history, clinical examinations, laboratory tests and ECG. Patients and parents are interviewed about tolerability

  24 months

Secondary Outcomes (4)

• Change in C-peptide fasting and 90 minute value during an MMTT from baseline to month 24

  24 months

• Proportion of patients with peak C-peptide > 0.20 nmol/l at month 24

  24 months

• Hemoglobin A1c (HbA1c), change between baseline and subsequent visits

  24 months

• Insulin dose/kg body weight/24 hrs

  24 months

Study Arms (3)

Part A: Open label intervention for 6 patients

EXPERIMENTAL

Intervention: Open label pilot arm with Verapamil treatment

Drug: Verapamil (Part A)

Part B: Active treatment with Verapamil in a double blind randomized controlled trial

ACTIVE COMPARATOR

Active treatment with Verapamil 3-6 mg/ kg body weight and 24 hrs in a double blind randomized controlled trial

Drug: Verapamil (Part A)

Part B: Placebo arm in a double blind randomized controlled trial

PLACEBO COMPARATOR

Placebo given in the same way and times as the active treatment, for 12 months

Drug: Placebo

Interventions

Verapamil (Part A) DRUG

Verapamil 3-6mg/kg body weight and 24 hrs

Also known as: Isoptin

Part A: Open label intervention for 6 patients; Part B: Active treatment with Verapamil in a double blind randomized controlled trial

Placebo DRUG

Placebo given in part B, the comparator arm of the double blind randomized trial

Part B: Placebo arm in a double blind randomized controlled trial

Eligibility Criteria

• Age: 4 Years - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnny Ludvigsson: lead
• Region Östergötland: collaborator
• Region Jönköping County: collaborator

Study Sites (2)

Pediatric Clinic , Ryhovs hospital

Jönköping, Sweden

NOT YET RECRUITING

Crown Princess Victoria Children´s Hospital, University Hospital

Linköping, SE58185, Sweden

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Verapamil

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Central Study Contacts

Johnny Ludvigsson, MD PhD

CONTACT

+46706577234; Johnny.Ludvigsson@liu.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Part A open study including 6 patients, and thereafter part B, a double-blind, randomized, placebo-controlled trial including 30 patients

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 30, 2025
• Study Start: August 6, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

SE (2)