Sirolimus for Retinal Astrocytic Hamartoma

NCT ID: NCT04707209

Last Updated: 2024-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-04
• Study Completion Date: 2024-03-22

Brief Summary

A single patient study using intravitreal Sirolimus to treat a patient with multiple retinal astrocytic hamartomas (RAH) of both eyes.

Detailed Description

Retinal astrocytic hamartomas (RAH) are benign tumors of glial cells arising from astrocytes in the nerve-fiber layer of the retina. They are often associated with tuberous sclerosis complex (TSC) and, more rarely, neurofibromatosis type 1 (NF1). RAH may be caused by dysregulated tumor suppressors genes TSC1 or TSC2, which play a role in cell cycle regulation in retinal astrocytes via the PDGF-signalling pathway. Downregulation of TSC1 or TSC2 can result in hyperactivation of mTOR. Sirolimus is an inhibitor of mTOR, therefore inhibiting cell growth and proliferation of astrocytes. Systemic mTOR inhibitors (sirolimus and everolimus) have shown impressive reduction in the size of RAH in animal models and many human case series.

This single patient study is investigating the use of concurrent oral and intravitreal Sirolimus to treat a patient with multiple retinal astrocytic hamartomas (RAH) of both eyes to improve intraocular response and reduce duration of treatment. The patient has no other clinical features suggestive of neurofibromatosis and a presumed diagnosis of tuberous sclerosis is being considered, with only two hypopigmented skin lesions noted.

Conditions

Retinal Astrocytic Hamartoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravitreal Sirolimus

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

An intravitreal injection of 20 µL of drug will be given through the pars plana of the eye. The injected eye will be treated with topical antibiotic and steroid eye drops prescribed for 7 to 10 days after the injection. The first injection will only be provided into the worse eye despite both eyes showing signs of exudation. Injection into the other eye will be considered only two months after the safety of this first injection is determined.

Safety and efficacy of treatment will be determined by repeat eye examinations in the eye clinic one day, one week and one month after each injection.

The interval between injections is roughly suggested to be between 3 to 8 weeks based on the drug deposit present in the eye. A total of 3-12 injections will be given per eye, over 6-24 months.

Interventions

Sirolimus

An intravitreal injection of 20 µL of drug will be given through the pars plana of the eye. The injected eye will be treated with topical antibiotic and steroid eye drops prescribed for 7 to 10 days after the injection. The first injection will only be provided into the worse eye despite both eyes showing signs of exudation. Injection into the other eye will be considered only two months after the safety of this first injection is determined.

Safety and efficacy of treatment will be determined by repeat eye examinations in the eye clinic one day, one week and one month after each injection.

The interval between injections is roughly suggested to be between 3 to 8 weeks based on the drug deposit present in the eye. A total of 3-12 injections will be given per eye, over 6-24 months.

Intervention Type: DRUG

Other Intervention Names

DE-109

Eligibility Criteria

Inclusion Criteria

Single case diagnosed with multiple retinal astrocytic hamartomas (RAH) of both eyes with imminent threat to vision.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Ashwin Mallipatna

Paediatric Ophthalmologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

1000072947

Identifier Type: -

Identifier Source: org_study_id