Health TrialsbyHealthPanel

Propranolol and Von Hippel-Lindau Disease

ConditionsHemangioblastoma of CNSVon Hippel-Lindau Disease
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

chronic obstructive pulmonary disease and asthma,

uncontrolled heart failure,

2nd and 3rd degree atrioventricular blocks,

bradycardia (<50 beats/minute after 3 minutes of rest),

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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

  • follow-up

    Other intervention

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

Treatment groups

85 Participants
are divided into 2 treatment groups
Group A: Experimental armExperimental treatment 1 intervention
Group B: control armOther 1 intervention

Trial outcomes

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

Time frame
24 months

Secondary outcomes

1

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

To study safety (tolerability) of propranolol in VHL patients: All adverse events related to the use of Propanolol that occurred during the study will be collected, analyzed and compared between the two treatment arms

Time frame
24 months
2

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

To compare HB growth rate between the two treatment arms at 24 months post-randomization: HB growth rate will be measured on each MRI by two neuroradiologists, blinded to the randomization arm. It will be calculated in mm3 /month using the function available on the ITK-SNAP imaging software ( www.itksnap.org.) which allows an accurate measurement of the tumor volume (In case of disagreement a conciliation session will be organized). The growth rate is therefore obtained by dividing the change in volume by the number of months between the two MRIs

Time frame
24 months
3

Compare the extent of peritumoral edema between the two treatment arms

To compare the extent of peritumoral edema between the two treatment arms: The size of peritumoral edema will be measured on each MRI by two neuroradiologists, blinded to the randomization arm

Time frame
24 months
4

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

To compare the occurrence of de novo lesions between the two treatment arms: the number of de novo HBs will be specified for each patient at each follow-up MRI by two neuroradiologists, blinded to the randomization arm. A de novo HB is defined as the appearance during follow-up of a HB that did not exist on the initial imaging (or the transition from a non-measurable HB to a measurable state

Time frame
24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Assistance Publique - Hôpitaux de Paris

Lead sponsor

Agence Générale des Equipements et Produits de Santé

Collaborator

Source ClinicalTrials.gov
Apply now