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EpilepsyPhase 1/2NCT01070316

Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC)

A Phase 1/2 study testing Everolimus in people with Epilepsy and Tuberous Sclerosis Complex, run by Children's Hospital Medical Center, Cincinnati at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this study is to learn if the study drug RAD001 can reduced the number of epileptic seizures, and can be taken safety by people who have epilepsy associated with Tuberous Sclerosis Complex. Read more about this study

Who is it for?
Ages 2 years and older
Conditions the study is for
Epilepsy, Tuberous Sclerosis Complex
What is being tested?
Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesUnited States
Study dates
Jan 2010to Apr 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • 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
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Baylor College of Medicine

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex

The goal of this study is to learn if the study drug RAD001 can reduced the number of epileptic seizures, and can be taken safety by people who have epilepsy associated with Tuberous Sclerosis Complex.

Read the detailed description

Tuberous sclerosis complex (TSC) is a genetic disorder with an incidence at birth of 1 in 6000. This disorder is characterized by the development of benign tumors in multiple organ systems, including the brain. The primary neurological manifestations of TSC are epilepsy, mental retardation and autism. Epilepsy is most common, occurring in 80-90% of patients, and often the seizures are severe, unremitting, and uncontrolled by current anticonvulsant medications. It is generally accepted that the seizures arise from cortical and subcortical tubers and surrounding tissue in the brain. These tubers are caused by mutations in the tumor suppressor genes TSC1 or TSC2. The protein products of these genes, hamartin and tuberin, act as negative regulators of the PI3K/PKB(Akt)/mTOR signaling pathway that regulates cell growth and proliferation Everolimus is an immunosuppressant drug that also inhibits mTOR signaling and is capable of reversing aberrant mTOR-dependent effects that occur when hamartin or tuberin are absent or defective. Thus, we hypothesize that drugs like everolimus may be therapeutically useful for the treatment of refractory epilepsy in patients with TSC.

Being tested
Everolimus
Keywords
Epilepsy, Tuberous Sclerosis Complex, Everolimus, RAD001, Mammalian Target of Rapamycin (MTOR)
Medical subject headings
Epilepsy, Tuberous Sclerosis, Hereditary Sensory and Autonomic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called RAD001, Certican, Afinitor

    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

Study groups in NCT01070316
Study groupRoleWhat they receive
EverolimusExperimentalSubjects 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.
Receives: Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction in Seizure Frequency

    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)

    Measured: Baseline (Weeks 1-4), Week 16

  2. Number of Participants Continuing Study Medication Over Time

    Measured: Individual subjects will be assessed every 6 months for up to 48 months; aggregate analysis will take place at end of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2010 (estimated)
  2. Study startJan 2010
  3. Primary completionApr 2016
  4. Study completionApr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01070316
Sponsor's protocol ID
2009-0998
Status last verified
Feb 2017
First submitted
15 Feb 2010
Last updated
13 Mar 2017
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Krueger DA, Wilfong AA, Holland-Bouley K, Anderson AE, Agricola K, Tudor C, Mays M, Lopez CM, Kim MO, Franz DN. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neurol. 2013 Nov;74(5):679-87. doi: 10.1002/ana.23960. Epub 2013 Sep 10.

    PubMed 23798472

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Everolimus in people with Epilepsy and Tuberous Sclerosis Complex, run by Children's Hospital Medical Center, Cincinnati at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction in Seizure Frequency (time frame: Baseline (Weeks 1-4), Week 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01070316, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2017.

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