Cantú syndrome
Conditions
Interventions
Trade Name: Glibenclamide Teva 5 mg, tabletten
Pharmaceutical Form: Tablet
Sponsors
Academic Medical Center Amsterdam
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. As the majority of CS patients reveal a mutation in ABCC9 and we aim to create a homogenized study population, only, otherwise healthy, patients with a confirmed diagnosis of CS via molecular genetic testing, with a mutation in ABCC9 will be eligible. 2. 16 years of age or older. 3. No history of sulfonamides or thiazides allergies. Are the trial subjects under 18? yes Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. All patients without a molecularly proven diagnosis of Cantú syndrome are excluded from this study. 2. Patients with a history of a sulfonamides or thiazides allergy 3. CS patients who are deemed poor candidates by the PI for the study based on additional medical concerns, not related to CS, including epilepsy, diabetes mellitus, intellectual deficit. As far as we are aware there are no cases in our cohort who are now suffering from additional medical concerns. 4. Pregnant women. 5. Patients with known G6PD deficiency. 6. Patients with known chronic kidney or liver disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal aim of this proof-of-concept exploratory study is to determine whether a full randomised controlled trial to test glibenclamide in a large cohort of CS patients is justifiable and feasible and to optimize its design. We specifically intend to assess the efficacy and safety of glibenclamide in individuals with CS. Primary objective: To determine whether treating CS patients with glibencamide can reduce hypertrichosis. Thus, we will perform dermascopy before and after treatment to assess changes in the amount of hair follicle in predefined body areas as well as measure thickness, density and growth of hair. ;Secondary Objective: Secondary objectives involve safety, further evidence of efficacy and collecting of experience and data that can be used to optimize a subsequent pivotal study. 1. We will determine safety of glibenclamide in CS patients. The main concern of treating CS patients with glibenclamide is that individuals who do not have diabetes are at risk to develop hypoglycemia. 2. To determine efficacy of glibenclamide in reversing (I would use “reducing”) (i) cardiovascular abnormalities focusing on cardiomegaly, aortic dilation, tortuosity, high-state output and exercise intolerance, (ii) swelling/edema in the leg, (iii) distinctive facial features as described in Roessler et al. and (iv) further skin- and hair-related abnormalities associated with CS. 2. To collect data for adequate sample size calculations for the primary outcome measures for use in a future full-scale phase II/III trial. 3. To estimate treatment period, appropriate outcome measurements and effect size for future trial. ;Primary end point(s): The primary outcome parameter of the exploratory study will be the mean change in the number of hair follicle per cm2 in predefined body areas affected with hypertrichosis (cheek, forehead, arm). Dermascopy pictures will be taken and evaluated using a computerized system (either Folliscope or Trichoscan). The system is a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcome parameters will include parameters of safety and efficacy of glibenclamide in treating cardiovascular, lymphatic, facial and dermatological effects of this condition. Based on our data from natural history studies collected over the past 5 years, we have identified a number of clinical characteristics whose possible reduction we intend to investigate during chronic exposure to glibenclamide. 1. Hypoglycemic events (safety parameter) The prevalence of dose-related minor and major hypoglycemic events will be assessed. Patients will be provided with a continuous glucose sensor and instructed by a specialized nurse how to handle in case of low blood glucose and recognize hypoglycemic symptoms. They will upload their 24h glucose profiles daily during the 2x2 weeks run-in period and weekly thereafter. Hypoglycemia will be categorized as follows (EMA 2012): documented symptomatic hypoglycemia (blood glucose 3.9 mmol/L). 2. Change from baseline in cardiovascular abnormalities Cardiovascular abnormalities will be evaluated by MRI, echocardiography, 24-hour heart rhythm monitoring and standard cardiac exercise test. 3. Changes from baseline in swelling/edema in the leg Edema will be measured applying method of Kuhnke (Kuhnke & Asdonk, 1986) where measurement of leg circumference by tape will be taken at the malleolar level and every 4 cm for eight leg segments. 4. Change from baseline in facial abnormalities 3D images of the face will be taken and analyzed using dense surface modelling and closest mean classification as described in Roessler et al. (2020) 5. Changes from baseline in dermatological abnormalities We will take clinical photographs of body parts with hypertrichosis, collect hair samples and take a scalp/forehead biopsy as described in Ohko et al. (2020). Patient satisfaction with hair growth and frequency of shaving necessary will be measured by asking patients to fill in a questionnaire including a Likert scale. 6. Chan | — |
Countries
Netherlands
Contacts
Public ContactMieke van Haelst
Academic Medical Center Amsterdam
Outcome results
None listed