Propranolol and Von Hippel-Lindau Disease

• Status: Not yet recruiting
• Trial end date: 2026-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Agence Générale des Equipements et Produits de Santé
• Treatments: Propranolol

Criteria

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