Propranolol for Von Hippel-Lindau disease

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- VHL patients with one or more central nervous system hemangioblastomas (HB) none of which require urgent surgical intervention (within 3 months)"}
• {"criterion_text":"- Patients who have provided written consent to participate in the study"}
• {"criterion_text":"- Affiliation with a social security scheme or dependent status"}

Exclusion criteria

• {"criterion_text":"- Chronic obstructive pulmonary disease and asthma"}
• {"criterion_text":"- Sick sinus syndrome (including sinoatrial block)"}
• {"criterion_text":"- Untreated pheochromocytoma"}
• {"criterion_text":"- History of anaphylactic reaction"}
• {"criterion_text":"- In the context of primary and secondary prevention of gastrointestinal hemorrhages in cirrhotics: advanced liver failure with hyperbilirubinemia, massive ascites, hepatic encephalopathy"}
• {"criterion_text":"- Predisposition to hypoglycemia (such as after fasting or in case of abnormal response to hypoglycemia)"}
• {"criterion_text":"- Metabolic acidosis"}
• {"criterion_text":"- Contraindications for MRI: •\tClaustrophobia •\tPresence of a pacemaker and other stimulators/implants •\tMetallic foreign bodies in the eyes •\tFerromagnetic cardiac valves or vascular clips •\tPatients already on propranolol or another beta-blocker •\tPatients under guardianship or conservatorship, or under judicial protection •\tPregnant or breastfeeding women •\tWomen planning a pregnancy in the medium term"}
• {"criterion_text":"- Uncontrolled heart failure"}
• {"criterion_text":"- Second- and third-degree atrioventricular blocks"}
• {"criterion_text":"- Bradycardia (<50 beats/minute after 3 minutes of rest)"}
• {"criterion_text":"- Raynaud's phenomenon and severe peripheral arterial disease"}
• {"criterion_text":"- Hypotension"}
• {"criterion_text":"- Hypersensitivity to propranolol"}
• {"criterion_text":"- Cardiogenic shock"}
• {"criterion_text":"- Prinzmetal angina"}

Primary endpoints

• {"endpoint_text":"- Effectiveness will be assessed using the proportion of patients responding to treatment with propranolol at 24 months post-randomization. The treatment response at 24 months will be a binary variable (responder/non-responder), evaluated by two neuroradiologists independently. They will be blinded to the randomization group.","definition_or_measurement_approach":"The treatment response at 24 months will be a binary variable (responder/non-responder), evaluated by two neuroradiologists independently; neuroradiologists are blinded to randomization group."}

Secondary endpoints

• {"endpoint_text":"- To study the safety of use (tolerance) at 24 months post-randomization: All adverse events related to the use of propranolol occurring during the study will be collected, analyzed, and compared between the two treatment arms.","definition_or_measurement_approach":"All adverse events related to propranolol occurring during the study will be collected, analyzed, and compared between the two arms at 24 months post-randomization."}
• {"endpoint_text":"- To compare the growth rate of hemangioblastomas (HB) between the two treatment arms at 24 months post-randomization: The growth rate of HB will be measured on each MRI (every 6 months) 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 for accurate measurement of tumor volume (in case of disagreement, a reconciliation session will be organized).","definition_or_measurement_approach":"Growth rate measured on each MRI every 6 months by two blinded neuroradiologists; calculated in mm³/month using ITK-SNAP tumor volume function; reconciliation session if disagreement."}
• {"endpoint_text":"- To compare the extent of peritumoral edema between the two treatment arms: The size of the peritumoral edema will be measured on each MRI (every 6 months) by two neuroradiologists, blinded to the randomization arm.","definition_or_measurement_approach":"Peritumoral edema size measured on each MRI every 6 months by two blinded neuroradiologists."}
• {"endpoint_text":"- To compare the occurrence of de novo lesions between the two treatment arms: The number of de novo HB will be specified for each patient at each control MRI (every 6 months) by two neuroradiologists, blinded to the randomization arm. A de novo HB is defined as the appearance during follow-up of an HB that did not exist on the initial imaging (or the transition from a non-measurable HB to a measurable state).","definition_or_measurement_approach":"De novo HB counted at each control MRI every 6 months by two blinded neuroradiologists; de novo defined as appearance absent on initial imaging or transition from non-measurable to measurable."}
• {"endpoint_text":"- To compare the angiogenic profile of HB between the two groups every 6 months through a perfusion sequence with r-CBV measurement for each measurable and perfusable lesion (> 1 cm).","definition_or_measurement_approach":"Perfusion sequence with r-CBV measurement for each measurable and perfusable lesion (>1 cm) every 6 months."}
• {"endpoint_text":"- To study the evolution of serum VEGF levels under treatment: Serum VEGF levels will be measured at the start of treatment, then at 12 and 24 months through a simple peripheral venous blood draw.","definition_or_measurement_approach":"Serum VEGF measured at baseline, 12 months, and 24 months via peripheral venous blood draw."}
• {"endpoint_text":"- To compare the number of patients requiring surgery between the two treatment arms: The need for surgery will be recorded during patient follow-up (surgery/no surgery). The necessity for surgery will be left to the discretion of the physician responsible for the patient’s follow-up.","definition_or_measurement_approach":"Number of patients requiring surgery recorded during follow-up (surgery/no surgery); indication for surgery at physician discretion."}
• {"endpoint_text":"- To compare the degree of autonomy and quality of life of patients between the two treatment arms: The degree of autonomy of each patient will be assessed using the Karnofsky index, mRS, ECOG Performance Status, and SF-36 every 6 months","definition_or_measurement_approach":"Degree of autonomy and QoL assessed every 6 months using Karnofsky index, mRS, ECOG Performance Status, and SF-36."}

France

Earliest CTIS Part Ii Submission Date

09-10-2024

Latest Decision Or Authorization Date

16-10-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

85

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"DGOS (Direction Générale de l'Offre de Soins), Ministry of Health, France","duties_or_roles":"Source of monetary support","organisation_type":""}