Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC)
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ClinicalTrials.gov Identifier: NCT01070316 |
Recruitment Status
:
Completed
First Posted
: February 18, 2010
Results First Posted
: September 23, 2016
Last Update Posted
: March 13, 2017
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Condition or disease | Intervention/treatment | Phase |
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Epilepsy Tuberous Sclerosis Complex | Drug: Everolimus | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 20 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex |
Study Start Date : | January 2010 |
Actual Primary Completion Date : | April 2016 |
Actual Study Completion Date : | April 2016 |

Arm | Intervention/treatment |
---|---|
Experimental: Everolimus
Subjects will be administered study drug if they meet study criteria after 4 weeks of baseline phase. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily.
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Drug: Everolimus
Everolimus is available in tablet form. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily. After two weeks, serum trough level will be measured and dose adjusted according to the following algorithm If Blood trough level is less than 2.5 ng/ml than increase dose by 5 mg/m2/day; If Blood trough level is 2.5-5.0 ng/ml than increase dose by 2.5 mg/m2/day; If Blood trough level is 5.1-10.0 ng/ml than increase dose by 0 mg/m2/day (no change); If Blood trough level is 10.1-15.0 ng/ml than decrease dose by 2.5 mg/m2/day
Other Names:
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- Reduction in Seizure Frequency [ Time Frame: Baseline (Weeks 1-4), Week 16 ]The primary efficacy endpoint was the percentage of participants demonstrating a 50% or greater reduction in seizure frequency at the end of the maintenance phase (weeks 13-16) compared to baseline (weeks 1-4)
- Number of Participants Continuing Study Medication Over Time [ Time Frame: Individual subjects will be assessed every 6 months for up to 48 months; aggregate analysis will take place at end of study ]

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Ages Eligible for Study: | 2 Years and older (Child, Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female individuals aged two years and older.
- History of epilepsy and at least eight reported seizures in previous 30 days prior to informed consent
- Failure of two or more approved antiepileptic drug therapies
- Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria or positive genetic test)
- Parents/Caregivers are English-speaking (primary or secondary language acceptable)
- If female and of child bearing potential, documentation of negative pregnancy test at time of informed consent. Sexually active pre-menopausal female or male patients must use adequate contraceptive measures, excluding use of estrogen-containing birth control contraceptive regimen while on study medication. Prior hysterectomy, tubal ligation, complete abstinence, barrier methods which include both a cervical diaphragm and spermicidal jelly, intrauterine devices (IUD), progesterone based contraceptives, or vasectomy in partner are all acceptable forms of contraception
- Adequate bone marrow function as shown by ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, and Hb >9 g/dL
- Adequate liver function as shown by serum bilirubin ≤ 1.5 x upper limit of normal (ULN), ALT and AST ≤ 2.5x ULN, INR and PTT ≤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 at time of randomization.)
- Adequate renal function as shown by a serum creatinine ≤ 1.5 x ULN
- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
Exclusion Criteria:
- Significant hematological or hepatic abnormality (i.e., transaminase levels > 2.5 x ULN or serum bilirubin >1.5 x ULN, Hemoglobin < 9 g/dL, platelets < < 100 X 109/L , absolute neutrophil count < 1.5 x 109/L)
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
- Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, 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 study
- Prior treatment with any investigational drug within the preceding 4 weeks prior to informed consent
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed
- Patients should not receive immunization with attenuated live vaccines within one week of informed consent or during study period
- Patients with coexisting malignancies within past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
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Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York heart Association Class III or IV, unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air and/or requirement for continuous supplemental O2
- Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
- Active (acute or chronic) or uncontrolled severe infections
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Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- A known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
- Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycin (sirolimus, temsirolimus) or to its excipients
- History of noncompliance to medical regimens

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01070316
United States, Ohio | |
Cincinnati Children's Hospital Medical Center | |
Cincinnati, Ohio, United States, 45229 | |
United States, Texas | |
Baylor College of Medicine | |
Houston, Texas, United States, 77030 |
Principal Investigator: | Darcy Krueger, M.D. Ph.D | Children's Hospital Medical Center, Cincinnati |
Publications of Results:
Responsible Party: | Children's Hospital Medical Center, Cincinnati |
ClinicalTrials.gov Identifier: | NCT01070316 History of Changes |
Other Study ID Numbers: |
2009-0998 |
First Posted: | February 18, 2010 Key Record Dates |
Results First Posted: | September 23, 2016 |
Last Update Posted: | March 13, 2017 |
Last Verified: | February 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Keywords provided by Children's Hospital Medical Center, Cincinnati:
Epilepsy Tuberous Sclerosis Complex Everolimus RAD001 Mammalian Target of Rapamycin (MTOR) |
Additional relevant MeSH terms:
Tuberous Sclerosis Sclerosis Epilepsy Pathologic Processes Brain Diseases Central Nervous System Diseases Nervous System Diseases Hamartoma Neoplasms Neoplasms, Multiple Primary Neoplastic Syndromes, Hereditary Malformations of Cortical Development, Group I Malformations of Cortical Development Nervous System Malformations Neurocutaneous Syndromes |
Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Congenital Abnormalities Genetic Diseases, Inborn Everolimus Sirolimus Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents |