Sirolimus for Retinal Astrocytic Hamartoma

Retinal Astrocytic Hamartoma Clinical Trial

Official title:

Intravitreal Injection of Sirolimus in the Treatment of Aggressive Retinal Astrocytic Hamartoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04707209
• Other study ID #: 1000072947
• Status: Completed
• Phase: N/A
• Start date: November 4, 2020
• Est. completion date: March 22, 2024

Study information

• Verified date: March 2024
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1
• Est. completion date: March 22, 2024
• Est. primary completion date: March 22, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 15 Years to 16 Years

Eligibility

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

Related Conditions & MeSH terms

• Retinal Astrocytic Hamartoma

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Size of Retinal Astrocytic Hamartomas compared to baseline	Measured by ophthalmic imaging	21 months
Primary	Amount of retinal exudate compared to baseline	Measured by ophthalmic imaging	21 months
Primary	Retinal detachment progression/regression compared to baseline	Measured by ophthalmic imaging	21 months
Secondary	Visual acuity compared to baseline	Measured using logMAR virtual activity test	21 months