Phase 2
N=15
A Pilot Study To Evaluate The Effects of Everolimus on Brain mTOR Activity and Cortical Hyperexcitability in TSC and FCD
Epilepsy · Tuberous Sclerosis Complex · Focal Cortical Dysplasia
Bottom Line
View on ClinicalTrials.gov: NCT02451696 ↗Enrolled (actual)
15
Serious AEs
0.0%
Results posted
Sep 2021
Primary outcome: Primary: Number of Patients With Adverse Events — 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Everolimus (Drug)
- Age
- Pediatric, Adult · 2+ yrs
- Sex
- All
- Sponsor
- NYU Langone Health
- Primary completion
- Dec 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Adverse Events |
0; 0 | — |
| SECONDARY Blood Everolimus Levels |
12.35; 2 | — |
| SECONDARY Blood Total VEGF Levels (Not Only VEGF-D) |
56.5; 50.85 | — |
| SECONDARY mTOR Brain Tissue-S6 Phosphate by Western Blot |
0.49; 0.81 | — |
| SECONDARY HMGB1 Expression in Brain Tissue |
14.85; 15.06 | — |
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
- 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)
- Patients: 1 year to 40 years. Matched for age (+/- 7 years) and sex of subjects in the treatment group.
- Diagnosis: treatment resistant due to TSC or FCD. Matched for diagnosis of TSC and FCD.
- Brain surgery for seizure control in which tissue is banked for research utilizing an existing IRB-approved study.
Exclusion Criteria
- Treatment with an mTOR inhibitor (everolimus, sirolimus) during the past four weeks.
- Known hypersensitivity to an mTOR inhibitor (everolimus, sirolimus)
- Failure to establish diagnosis of treatment resistant epilepsy (i.e., adequate trials of two appropriately-chosen, tolerated and adequate trials of antiepileptic drugs) [32].
- Exposure to any investigational agent in the month prior to study entry.
- History of malignancy patients who are receiving anti-cancer treatments, such as radiation therapy and/or chemotherapy.
- Patients with severe and/or uncontrolled medical conditions,
- Patients on chronic corticosteroid therapy
- A history of HIV seropositivity
- Patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study;
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus;
- Uncontrolled diabetes mellitus
- Patients who have any severe and/or uncontrolled medical conditions
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus;
Data sourced from ClinicalTrials.gov (NCT02451696). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.