A Pilot Study To Evaluate The Effects of Everolimus on Brain mTOR Activity and Cortical Hyperexcitability in TSC and FCD
Condition: Epilepsy; Tuberous Sclerosis Complex; Focal Cortical Dysplasia
MeSH terms: Tuberous Sclerosis; Malformations of Cortical Development; Focal Cortical Dysplasia
Intervention: Everolimus
Intervention description: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 2 Years
Maximum age: 40 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to measure if the drug called Everolimus effects mTOR signaling
      (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex
      (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be
      undergoing brain surgery. One group of patients will be treated with Everolimus, and another
      will not. Researchers will determine if there is a difference in mTOR signaling between the
      patients who were treated with Everolimus and those who were not. Previous studies have
      suggested that Everolimus may reduce seizure activity in TSC patients by decreasing mTOR
      signaling. Since patients with FCD may also have excess mTOR signaling brain activity,
      Everolimus may also reduce seizure activity in these patients.

      The drug Everolimus is approved by the Food and Drug Administration to treat specific types
      of breast, pancreatic, and kidney cancer, a kidney tumor called an angiomyolipoma (common in
      patients with TSC), and TSC patients who have a brain tumor called a subependymal giant cell
      astrocytoma (SEGA). However, in this research it is considered to be an investigational since
      it is not approved for reduction in mTOR signaling and a decrease in seizure frequency.
      Researchers believe that Everolimus may be useful in reducing something called cortical
      hyperexcitability, which is the excess brain activity that can contribute to seizures.
    

Eligibility criteria:

        Inclusion Criteria

        1. Patients: 1 year to 40 years. 2. Diagnosis: treatment resistant epilepsy due to Tuberous
        Sclerosis Complex or Focal Cortical Dysplasia Inclusion Criteria (Concurrent Comparison
        Group)

          1. Patients: 1 year to 40 years. Matched for age (+/- 7 years) and sex of subjects in the
             treatment group.

          2. Diagnosis: treatment resistant due to TSC or FCD. Matched for diagnosis of TSC and
             FCD.

          3. Brain surgery for seizure control in which tissue is banked for research utilizing an
             existing IRB-approved study.

        Exclusion Criteria

          1. Treatment with an mTOR inhibitor (everolimus, sirolimus) during the past four weeks.

          2. Known hypersensitivity to an mTOR inhibitor (everolimus, sirolimus)

          3. Failure to establish diagnosis of treatment resistant epilepsy (i.e., adequate trials
             of two appropriately-chosen, tolerated and adequate trials of antiepileptic drugs)
             [32].

          4. Exposure to any investigational agent in the month prior to study entry.

          5. History of malignancy patients who are receiving anti-cancer treatments, such as
             radiation therapy and/or chemotherapy.

          6. Patients with severe and/or uncontrolled medical conditions,

          7. Patients on chronic corticosteroid therapy

          8. A history of HIV seropositivity

          9. Patients who have received live attenuated vaccines within 1 week of start of
             everolimus and during the study;

         10. Known impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of oral everolimus;

         11. Uncontrolled diabetes mellitus

         12. Patients who have any severe and/or uncontrolled medical conditions

         13. Known impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of oral everolimus;