Tuberous Sclerosis Complex: Facial Angiofibroma Skin Cream

This is an open label, prospective single center study. Patients that are seen in our
regional Tuberous Sclerosis Complex Clinic and have facial angiofibromas that would benefit
from this cream and who wish to be involved in this study would be enrolled. We anticipate
enrolling 12-15 patients the first year. Patients will have pictures of their facial
angiofibromas taken immediately prior to entry into the study. They will then be prescribed
0.1% rapamune topical formulation to apply twice daily to their skin for the first two weeks
and then once daily. If level is above 0, will re-check serum lipids, cbc, and repeat levels
every three-four months and monitor the patient for symptoms. Patients will return at one
month and three months to obtain serum rapamune levels along with pictures, then they will
be seen intermittently throughout the first year with photographs of their face taken at the
one month visit, 3 month visit, six month visit and twelve month visit. We will ask the
parents about any side effects from the medication during the entire time patients are using
the topical rapamune. We will monitor the facial lesions as well. We will assess for skin
sensitivity, pain, erythema, or pruritus. If skin irritation results from the drug, then we
will stop use of the drug. Parents will sign an informed consent allowing their child's
picture to be taken and allowing us to summarize the data for publication at the end of this
study.

This study will be the first study using a consistent formulation to make a 0.1% rapamune
cream, and this will be performed under the direction of myself and Dr. Almoazen in the
University of Tennessee Health Science Center(UTHSC) College of Pharmacy compounding
laboratory. Only patients who are thought to be reliable for the follow up visits and to use
the cream appropriately will be enrolled in the study. This study meets the FDA criteria for
an Investigational New Drug(IND) exemption.

The adverse events noted in the package insert for rapamune cream are all based on systemic
administration of the medication, primarily to adults with other diseases. In our clinical
experience, with topical use there is no absorption and we have not noted any side effects.

Inclusion Criteria:

- Patient or his / her legally authorize representative (LAR) must sign and date the
approved informed consent prior to study participation or initiation of study
procedures. If appropriate, the patient will give written or verbal consent.
Surrogate consent will be obtained utilizing the "legally authorized representative
(LAR)". The LAR must be an adult who has exhibited special care and concern for the
subject, who is familiar with the subject's personal values, who is reasonably
available, and who is willing to serve. No person who is identified as a protective
order or other court order that directs that person to avoid contact with the subject
shall be eligible to serve as the subject's LAR. Identification of LAR should
normally be made using the following order of descending preference: Conservator,
guardian, attorney in fact, subject's spouse (unless legally separated), the
subject's adult child, the subject's parent, the subject's adult sibling, any other
adult relative of the subject, or other adult who is familiar with the patient's
personal values, who is reasonably available, and who is willing to serve.

1. Patient must have a diagnosis of Tuberous Sclerosis Complex.

2. Female or male patients over the age of 3 years.

3. Female subjects of child bearing potential must not be pregnant and must undergo
a pregnancy test, and must agree to use appropriate contraceptive methods

Exclusion Criteria:

- Patients will be excluded from entry into the study if any of the following are true:

1. Patient has a history of drug allergy to rapamune.

2. Patient is pregnant or lactating.

3. Subject is receiving therapy with Rapamycin.

4. Subject is receiving any form of immunosuppression or has previously experienced
immune dysfunction.

5. Subject is currently participating in or has participated within the Last 30
days in a clinical trial involving an investigative drug.

6. Subject has other dermatologic conditions that would preclude or prevent
adequate assessment of changes to their facial angiofibromas.

7. Subject has had laser surgery, cryotherapy, or other dermatologic treatment to
their facial angiofibromas within the previous 6 months.