Propranolol and Von Hippel-Lindau Disease

NCT05424016 | Recruiting DMC

• 2 other identifiers: APHP2100752022-001174-54
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hemangioblastoma of CNS; Von Hippel-Lindau Disease

Keywords

hemangioblastomas; Propranolol; Von Hippel-Lindau,; MRI

Outcome Measures

Primary Outcomes (1)

• total and individual hemangioblastomas' volume measured by MRI

  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

  24 months

Secondary Outcomes (7)

• To compare the safety (tolerance) between the two treatment arms at 24 months post-randomization

  24 months

• To Compare the growth rate of HB between the two treatment arms at 24 months post-randomization

  24 months

• Compare the extent of peritumoral edema between the two treatment arms

  24 months

• Compare the development of de novo lesions between the two treatment arms every 6 months

  24 months

• Compare the angiogenic profile of BHs between the two groups every 6 months

  24 months

Study Arms (2)

Experimental arm

EXPERIMENTAL

Patients with no contraindications will be included and randomized to receive propranolol orally for 24 months

Drug: Propranolol

control arm

OTHER

Patient included with a routine follow-up

Other: follow-up

Interventions

Propranolol DRUG

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

Experimental arm

follow-up OTHER

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

control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Contraindication to the use of propranolol:
• chronic obstructive pulmonary disease and asthma,
• uncontrolled heart failure,
• nd 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Agence Générale des Equipements et Produits de Santé: collaborator

Study Sites (1)

AP-HP, Bicêtre Hospital

Le Kremlin-Bicêtre, 94275, France

RECRUITING

MeSH Terms

Conditions

von Hippel-Lindau Disease; Hemangioblastoma

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Hemangioma, Capillary; Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Central Study Contacts

AGHAKHANI Nozar, PR

CONTACT

+33145212380; nozar.aghakhani@aphp.fr

RICHARD Stéphane, PR

CONTACT

+33145217201; stephane.richard@univesite-paris-saclay.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-label, randomized, controlled trial with 2 parallel arms

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 21, 2022
• Study Start: January 16, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 13, 2023

Record last verified: 2023-12

Locations

FR (1)