Sirolimus for Retinal Astrocytic Hamartoma

Sponsor

The Hospital for Sick Children (Other)

Overall Status

Recruiting

CT.gov ID

NCT04707209

Collaborator

(none)

Enrollment

Location

Arm

13.9

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Retinal Astrocytic Hamartoma	Drug: Sirolimus	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 4, 2020

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravitreal Sirolimus	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. 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. Other Names: DE-109

Arm

Intervention/Treatment

Experimental: Intravitreal Sirolimus

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. 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.

Other Names:

DE-109

Outcome Measures

Primary Outcome Measures

Size of Retinal Astrocytic Hamartomas compared to baseline [14 months]
Measured by ophthalmic imaging
Amount of retinal exudate compared to baseline [14 months]
Measured by ophthalmic imaging
Retinal detachment progression/regression compared to baseline [14 months]
Measured by ophthalmic imaging

Secondary Outcome Measures

Visual acuity compared to baseline [14 months]
Measured using logMAR virtual activity test

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 16 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G1X8

Sponsors and Collaborators

The Hospital for Sick Children

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ashwin Mallipatna, Paediatric Ophthalmologist, The Hospital for Sick Children

ClinicalTrials.gov Identifier:

NCT04707209

Other Study ID Numbers:

1000072947

First Posted:

Jan 13, 2021

Last Update Posted:

Jan 13, 2021

Last Verified:

Jan 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Hamartoma

Sirolimus

Study Results

No Results Posted as of Jan 13, 2021