Objective
The primary objective of this proposed study is to explore the long-term effect of verapamil in patients with type 1 diabetes. The study will measure the amount of insulin that can be secreted by the ß-cells after two years of therapy with verapamil in addition to optimized insulin treatment. Secondary objectives are the changes of insulin secretion over time, the overall metabolic control, the rate of hypoglycaemia and ketoacidosis and the safety of Verapamil.
Background Rationale
Type 1 diabetes mellitus (T1DM) is a disorder that arises following the selective autoimmune destruction of the insulin-producing beta-cells. A cure for T1DM would aim at ensuring that the necessary insulin producing cell mass is preserved or increased. A large study in the past (The Diabetes Control and Complications Trial) has shown that even a small amount of preserved insulin production in patients with type 1 diabetes has beneficial effects in terms of outcome, overall glycaemic control and prevention of severe hypoglycaemia. The destruction of insulin-producing beta-cells is considered to be mainly due to immune system of the own body, and many efforts have been made to stop or modify this destruction. In parallel, attempts to replace insulin producing cells by transplantation are associated with potentially severe side effects due to the necessary change in the own immune system. Recently beta-cell protective or beta-cell regenerative approaches have gained wider attention, and new drugs to protect the patient’s own insulin-producing beta-cell mass have been investigated in animal experiments.
Verapamil belongs to a specific class of drugs that lowers blood pressure in patients with hypertension. This medication has been used worldwide in adults and children with evaluated blood pressure for more than three decades. Basic research in insulin producing cells has shown that verapamil triggers certain metabolic changes that can improve the survival of insulin producing cells. In a small clinical trial in newly diagnosed adults with type 1 diabetes verapamil has already demonstrated preservation of insulin secretion. The use of verapamil allowed protection of ß-cell function without any relevant drug side effects.
Description of Project
Type 1 diabetes affects more than 35 million individuals worldwide, with doubling of numbers expected in the coming 20 years in many countries. Many of the patients contract the disease already at young age, which makes the management a major challenge, for both, affected people and their relatives. One of the most frustrating moments in a medical doctor’s life is announcing the diagnosis of T1D to a patient and even more so to the parents of an affected child. At present, the only established therapeutic option for the caregivers is to initiate insulin therapy and just be a bystander while the immune system further destroys the remaining ß-cells.
Even with the best disease management, patients remain vulnerable to the devastating disease complications that damage in particular their eyes, kidneys, nerves and heart. While the importance of achieving normal blood glucose levels is clear, this therapy is particularly difficult. Hypoglycaemia, and more important severe hypoglycaemia has negative impact on lives and the wellbeing of patients, their families and friends, and has a negative impact on health care systems worldwide.
It is therefore an imperative to search for novel therapies that can modify the immune system in affected patients towards immune tolerance and utilize novel agents to protect the ß-cell from destruction. Protection of ß-cell function ameliorated the burden of the disease and has shown to protect patients from both, low and high blood glucose values and its consequences.
Verapamil belongs to a specific class of drugs that lowers blood pressure in patients with hypertension. This medication has been used worldwide in adults and children with evaluated blood pressure for more than three decades. Basic research in ß-cells has shown that verapamil triggers certain metabolic changes that can improve the survival of insulin producing ß-cells. In a small clinical trial in newly diagnosed adults with type 1 diabetes verapamil has already demonstrated preservation of insulin secretion. The use of verapamil allowed protection of ß-cell function without any relevant drug side effects. In an ongoing study, we are investigating the effect of verapamil after 1 year of treatment in a larger group of adults with newly diagnosed type 1 diabetes.
Currently, the Ver-A-T1D study is looking at how Verapamil affects adults with newly diagnosed T1D. More than 50 participants have already completed their treatment, and many more have not finished the treatment yet. Patients who are still participating in the Ver-A-T1D study now have the opportunity to take part in the Ver-A-Long study.
The aim of the Ver-A-Long study is to explore how a 24-month treatment with 360 mg of Verapamil SR helps to preserve the beta-cell function in adults with type 1 diabetes and to evaluate the safety of this long-term treatment.
Anticipated Outcome
This study will explore, if verapamil, a drug to treat elevated blood pressure, has a long-term effect on the preservation of insulin secretion in patients with type 1 diabetes. The study will help to assess the magnitude of the effect of two years therapy with verapamil, and it will measure other important factors of type 1 diabetes, such as metabolic control, insulin need over the day, and the risk of experiencing a hypoglycaemia.
Relevance to T1D
Type 1 diabetes affects more than 35 million individuals worldwide, with doubling of numbers expected in the coming 20 years in many countries. The majority of patients contract the disease at young age, with clinical presentation becoming more aggressive, leading to diagnosis in more children at younger ages. The diagnosis of type 1 diabetes has large impact since at present no cure exists and it affects individuals for the majority of their life.
New interventions with safe drugs that protect insulin producing cells have the chance to change the landscape of type 1 diabetes treatment. A longer preservation of insulin production will protect patients from adverse effects of both, too low and too high blood glucose values. The impact of the proposed study on people with T1D and their families will be of an even greater dimension, especially as a safe combination of drugs that protect insulin production with drugs that modify the immune system of the patient has a realistic chance to get closer to the cure of the disease.