Effect of Ivabradine on Adolescent Dysautonomia

Dysautonomia of Adolescence (dysautonomia) is an umbrella term used to describe symptoms experienced by adolescents and young adults related to dysfunction of the autonomic nervous system. Symptoms can include dizziness, fatigue, increased heart rate upon standing, exercise intolerance, and difficulty with daily activities. Treatment commonly involves lifestyle modifications, including increased fluid and salt intake and structured routines related to diet, sleep, aerobic exercise, and lower-body strength training. While these approaches can be effective, some patients experience symptoms that make it difficult to implement these changes. Despite increasing awareness of dysautonomia, research evaluating effective treatment strategies in adolescents remains limited, and there are currently no medications approved by Health Canada specifically for the treatment of dysautonomia. Ivabradine is a heart rate-lowering medication approved for the treatment of heart failure and has been studied as a potential treatment for symptoms associated with dysautonomia, including postural orthostatic tachycardia syndrome (POTS). However, there is limited evidence regarding its use in adolescents. The purpose of this randomized, double-blind, placebo-controlled study is to evaluate whether ivabradine can reduce symptom burden and improve heart rate control and overall well-being in adolescents with dysautonomia. The study will use a series of N-of-1 randomized controlled trials in which participants receive both ivabradine and placebo during different treatment periods. This design will allow the effects of ivabradine and placebo to be compared within individual participants.

Inclusion Criteria: • Diagnosis of dysautonomia of adolescence from the Dysautonomia Clinic in the Children's Heart Centre at BC Children's Hospital. Exclusion Criteria: * Patients who plan on becoming pregnant or who are pregnant. * Nursing mothers. * Patients with impaired kidney or liver function (based off last blood test within the past year if either is present consult the patient's nephrologist or hepatologist to determine risk of participation). * Patients with a diagnosis of long QT. * Patients on the following strong CYP3A4 inhibitors: Ketoconazole, Josamycin, Itraconazole, Clarithromycin, Nefazodone, Ritonavir, Atazanavir, Nelfinavir. * Patients on the following moderate CYP3A4 inhibitors: Diltiazem, Verapamil, Fluconazole. * Patients on the following CYP3A4 inducers: Rifampicin, Barbiturates, and Phenytoin. * Patients on any QT prolongating agents such as antiarrhythmics, antipsychotics, antidepressants, opiods, antibiotics, antimalarials, antifungals, 5-HT3 receptor antagonists, tyrosine kinase inhibitors, histone deacetylase inhibitors, beta-2 adrenoreceptor agonists and drugs such as domperidone, pentamidine.