Sirolimus for Retinal Astrocytic Hamartoma

Study Overview
=================
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.

Official Title
-----------------
Intravitreal Injection of Sirolimus in the Treatment of Aggressive Retinal Astrocytic Hamartoma

Conditions
-----------------
Retinal Astrocytic Hamartoma

Intervention / Treatment
-----------------
* Drug: Sirolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Single case diagnosed with multiple retinal astrocytic hamartomas (RAH) of both eyes with imminent threat to vision.

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravitreal Sirolimus<br> | Drug: Sirolimus<br>* 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. Injections will be repeated every eight weeks. A total of 3-6 injections will be given per eye, over 6-12 months. The current treatment plan is for a maximum of six injections per eye, which may be amended to accommodate more in the future.<br>* Other names: DE-109;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Size of Retinal Astrocytic Hamartomas compared to baseline | Measured by ophthalmic imaging | 14 months | 
| Amount of retinal exudate compared to baseline | Measured by ophthalmic imaging | 14 months | 
| Retinal detachment progression/regression compared to baseline | Measured by ophthalmic imaging | 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity compared to baseline | Measured using logMAR virtual activity test | 14 months |