6209: Pilot Clinical Drug Trial of Sirolimus for Cognitive Impairments in Sturge-Weber syndrome



This research is being done to study the safety and usefulness of the study drug Rapamune (sirolimus) for the treatment of cognitive impairments in Sturge-Weber syndrome brain involvement.


For Diseases:

  • Sturge-Weber syndrome


Children living with Sturge-Weber syndrome (SWS) urgently need more effective medications. Many children develop a range of cognitive impairments, including intellectual disability, attention deficit disorder, learning disabilities, and autism. Classic SWS consists of a vascular birthmark on the face, abnormal blood vessels in the eye, and a vascular malformation in the brain. The purpose of the study is to 1) gain a preliminary understanding of the safety, and 2) determine best outcomes to be used to assess the usefulness of sirolimus for the treatment of cognitive impairments in Sturge-Weber syndrome.

The research question is:

  1. Is sirolimus safe and effective in treating cognitive impairments in Sturge-Weber syndrome patients?

About this Study

This is an interventional pilot treatment study of 10 individuals with Sturge-Weber syndrome. Those participating in the study will be asked to meet with the Investigator in clinic for a minimum of six visits over six months. At each visit, participants will be asked to complete some or all of the following:

  • Give blood (approximately 2 teaspoons).
  • Have a physical performed, vitals, and weight collected.
  • Have a physical performed, vitals, and weight collected.
  • Have pictures taken of their port-wine birthmark (if present).
  • Give a urine sample (if female of child bearing potential).
  • Take the study drug (sirolimus) by mouth twice a day for up to six months.
  • Have an electroencephalogram (EEG: noninvasive test of the brain activity) and complete neuropsychological baseline testing.

We may look at your medical records from your local doctor’s office so that we can collect information about your medical history.

Participants may have the option to extend their participation in the study for up to 1.5 more years.


Targeted Enrollment

To be eligible to participate, you must:

  1. Have Sturge-Weber syndrome with brain involvement as defined on neuroimaging.
  2. Be 3 to 31 years of age.
  3. Have cognitive impairment as defined by the following:
    1. SWS cognitive neuroscore of ≥ 1
  4. Have the ability to participate in direct neuropsychological and developmental testing.
  5. Understand and speak English as your primary language.
  6. Be on stable anti-epileptic drugs (no changes in medications except dose for >3 months).
  7. Have adequate renal function. GFR must be greater than 50 ml/min/m2 as determined by the Schwartz Formula for children and MDRD for adults [GFR: Glomerular filtration rate tests how well the kidneys are working]
  8. Have a negative pregnancy test prior to enrollment as determined by a urine test (required for females of child bearing potential).
  9. Agree to use adequate contraceptive measures, excluding estrogen containing contraceptives, while on the study drug. Abstinence will be considered an adequate contraceptive measure.
  10. Have an INR ≤1.5 (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks.) [INR: International Normalised Ratio measures how much longer it takes the blood to clot when oral blood-thinners are used].
  11. Have adequate liver function as shown by:
    1. Serum bilirubin ≤ 1.5x ULN
    2. ALT and AST ≤ 2.5x ULN
  12. Be willing to sign informed consent according to local guidelines.
  13. Be on a stable dose of medications affecting the cytochrome P450 3A4 (CYP3A4) and p glycoprotein (P gp) systems for at least 3 months prior to consent.

You are not eligible to participate if you:

  1. Have an allergy to sirolimus or other rapamycin analogues.
  2. Have seizures secondary to metabolic, toxic, infectious or psychogenic disorder, drug abuse or current seizures related to an acute medical illness.
  3. Are unable to keep follow-up appointments, maintain close contact with Principal Investigators, and/or complete all necessary studies to maintain safety.
  4. Need immediate major surgical intervention.
  5. Have concurrent severe and/or uncontrolled medical disease, which could compromise participation in the pilot study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration, impaired or restrictive pulmonary function, pneumonitis or pulmonary infiltrates).
  6. Have chronic treatment with systemic steroids or another immunosuppressive agent.
    (Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary.  Inhaled steroids are allowed.)
  7. Have a known history of a positive HIV test or known immunodeficiency. (Testing is not required unless a condition is suspected.)
  8. Have an impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of sirolimus (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A gastric tube or nasogastric tube is allowed.
  9. Have an active, bleeding diathesis (unusual susceptibility to bleed).
  10. Have uncontrolled hyperlipidemia: a) fasting serum cholesterol > 300 mg/dL, and b) fasting triglycerides > 2.5 x ULN.
  11. Have had a major surgery or significant traumatic injury within four weeks of study entry. Patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the pilot study may not join.
  12. Have a prior history of organ transplant.
  13. Have received live attenuated vaccines within one week of start of sirolimus and during the pilot study.
  14. Have a history of malignancy.
  15. Currently are part of or have participated in any clinical investigation with an investigational drug within one month prior to enrollment.
  16. Are being treated with felbamate (an anticonvulsant), unless treatment has been continuous for ≥ one year.
  17. Currently receiving anticancer therapies or who have received anticancer therapies within four weeks of study entry (including chemotherapy, radiation therapy, antibody based therapy, etc.).

How to participate:

In order to participate, you must personally contact the study coordinator of any of the participating institutions by phone or by email. Please use the information below to inquire about participation:





  • Cincinnati Children's Hospital, Cincinnati
    Contact: Paula Mobberley-Schuman, MS
    Phone: 513-803-9255
    E-mail: HVMCResearch@cchmc.org