Propranolol and Von Hippel-Lindau Disease

NCT05424016 · tracked via the Priya Life Science France tracker

Sponsor

Assistance Publique - Hôpitaux de Paris

Phase

Not applicable

Started

2023-01-16

Last updated

2023-12-13

Condition(s) studied

Hemangioblastoma of CNSVon Hippel-Lindau Disease

Investigational drug(s) / intervention(s)

Propranolol →follow-up

Propranolol: 120 mg/d propranolol started in a progressive way (with control of Blood Pressure and heart rate during the consultations) neurosurgical consultation and an MRI every six months

follow-up: routine follow-up (neurosurgical consultation and an MRI every six months)

Study summary

Propranolol (beta-blocker), is successfully used for the treatment of infantile hemangiomas, the most common vascular tumor of newborns. The mechanism is related to its anti-angiogenetic and pro-apoptotic effects. Recently, in vitro studies demonstrated that propranolol decreased the expression of target genes of the HIF (hypoxia-inducible factor, of which the VHL gene is the main regulator) pathway in hemangioblastoma cells and affected their viability. The efficacy of propranolol (stabilization of all HB and decrease in serum VEGF levels) was demonstrated in a phase III study, but only in retinal BHs . The only study that evaluated the effect of propranolol on CNS HB was retrospective and involved a limited number of patients. Nevertheless, it showed a decrease in the growth rate of HBs. The investigator therefore propose to carry out a randomized controlled trial to study the effect of propranolol on the growth of CNS HB in patients with VHL disease (von Hippel-Lindau).

The hypothesis of the present work is the following: the use of propranolol in VHL patients with CNS HB allows to decrease and/or slow down the tumor growth.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

Inclusion Criteria: * Age ≥ 18 * VHL patient with one or more hemangioblastomas of the central nervous system, none of which require urgent surgery (within 3 months) * Patient with written consent to participate in the study * Enrolled in a social security plan or beneficiary Exclusion Criteria: * Contraindication to the use of propranolol: * chronic obstructive pulmonary disease and asthma, * uncontrolled heart failure, * 2nd and 3rd degree atrioventricular blocks, * bradycardia (\<50 beats/minute after 3 minutes of rest), * Raynaud's phenomenon and peripheral arterial disorders, * arterial hypotension, * hypersensitivity to propranolol * cardiogenic shock, * Prinzmetal's angina, * sinus disease (including sino-auricular block) * untreated pheochromocytoma, * history of anaphylactic reaction, * in the context of primary and secondary prevention of digestive bleeding in cirrhotics: advanced liver failure with hyperbilirubinemia, massive ascites, hepatic encephalopathy * predisposition to hypoglycemia (as after fasting or in case of abnormal response to hypoglycemia) * metabolic acidosis * Contraindication to MRI: * claustrophobia, * presence of a pace maker and other stimulators/implants * ocular metallic foreign bodies, * heart valves or ferromagnetic metal vascular clips * Patients already on Propranolol or other beta blockers * Patients under guardianship or conservatorship * Pregnant or breastfeeding women - Woman with a medium-term pregnancy project

Primary outcome measure(s)

total and individual hemangioblastomas' volume measured by MRI — 24 months
Response to treatment at 24 months will be a binary variable (responder/non responder) using initial imaging data and 24-month post-randomization, assessed by two neuroradiologists, independently. On baseline imaging two types of CNS BHs will be defined and measured: "measurable" BHs whose largest diameter is ≥ 5 mm "Non-measurable" BHs whose largest diameter is \< 5 mm For each patient the sum of the volumes of all measurable BHs in mm3 will be calculated initially and compared to this same sum at 24 months post-randomization. A patient will be as "responder" : The sum at 24 months remains stable Or regresses No HB identified as "non-measurable" initially has reached the "measurable" criterion No de novo HBs have appeared A patient will be as "non-responder": The sum at 24 months increases At least one HB identified as "non-measurable" initially has reached the "measurable" criterion At least one de novo HB appears The patient has required surgery during follow-up

Trial sites (1)

Facility	City	Region	Status
AP-HP, Bicêtre Hospital	Le Kremlin-Bicêtre	France	Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05424016 on ClinicalTrials.gov ↗ ← All trials in France