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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT01730209
Other study ID # NL38619.078.11
Secondary ID
Status Recruiting
Phase Phase 2/Phase 3
First received October 26, 2012
Last updated May 4, 2015
Start date November 2012
Est. completion date November 2016

Study information

Verified date May 2015
Source Erasmus Medical Center
Contact M.C.Y. de Wit, MD. PhD.
Phone +31 10 703 6956
Email tubereuzesclerose@erasmusmc.nl
Is FDA regulated No
Health authority Netherlands: Medical Ethics Review Committee (METC)
Study type Interventional

Clinical Trial Summary

Tuberous sclerosis complex (TSC) is a genetic disease that leads to mental retardation in over 50% of patients, and to learning problems, behavioral problems, autism and epilepsy in up to 90% of patients. The underlying deficit of TSC, loss of inhibition of the mammalian target of rapamycin (mTOR) protein due to dysfunction of the tuberin/hamartin protein complex, can be rescued by everolimus. Everolimus has been registered as treatment for renal cell carcinoma and giant cell astrocytoma (SEGA). Evidence in human and animal studies suggests that mTOR inhibitors improve learning and development in patients with TSC.


Description:

Randomized double-blind placebo controlled intervention study in children with TSC between age 4 and 15 years with an intelligence quotient (IQ) estimated <80 and/or special schooling and/or autism spectrum disorder and/or learning disability requiring remedial teaching.

Patients are randomised to receive everolimus or placebo during a period of 12 months.


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date November 2016
Est. primary completion date November 2015
Accepts healthy volunteers No
Gender Both
Age group 4 Years to 15 Years
Eligibility Inclusion Criteria:

- Children with a definite diagnosis of TSC between 4 and 15 years.

- With an IQ estimated <80 and/or special schooling and/or autism spectrum disorder and/or learning disability requiring remedial teaching.

- Written informed consent by parents/care-takers, and the patient if he or she is 12 years or older and cognitively able to consent.

- In girls after menarche, appropriate contraception must be used or abstinence practiced.

Exclusion Criteria:

- Hepatic dysfunction

- Surgery <6wk

- Current infection at time of inclusion

- Developmental age estimated below 3.5 years

- Intractable epilepsy with more than 1 seizure/week

- Inability to comply with the treatment protocol

- Additional diseases or disorders that may influence the endpoints, including:

- SEGA requiring treatment

- Uncontrolled diabetes mellitus

- Known impaired lung function

- Allergy for any of the components of the study medication

- Prior treatment with mTOR inhibitors

- HIV seropositivity

- Bleeding diathesis or oral anti-vitamin K medication

- Serum creatinine > 1.5 x ULN

- Uncontrolled hyperlipidemia (fasting serum cholesterol > 7.75 mmol/L, fasting serum triglycerides > 2.5 x ULN)

- Use of investigational drug within 30 days prior to inclusion

- History of myocardial infarction, angina or stroke related to atherosclerosis, organ transplantation, malignancy in the past 2 years

- Pregnancy or breastfeeding

- Children at risk for Hepatitis B (HB), unless hepatitis B serology is normal. Risk groups are children who have lived in Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal, and Greece, children with known or suspected past or current hepatitis B infection, current or prior IV illicit drug use, current or prior dialysis, household contact with hepatitis B infected patient(s), current or prior high-risk sexual activity, body piercing or tattoos, mother known to have hepatitis B history. If vaccinated, presence of HBs Ab is normal.

- Known or suspected hepatitis C infection, unless hepatitis C serology is normal.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

Drug:
Everolimus
Everolimus once daily titrated to trough levels of 5-10 ng/ml.
Placebo


Locations

Country Name City State
Netherlands Erasmus Medical Center Rotterdam

Sponsors (2)

Lead Sponsor Collaborator
Erasmus Medical Center Utrecht University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Other School level Assessed by the school CITO (centraal instituut voor toetsontwikkeling) scores or reading and arithmetic scores 12 Months No
Other Pharmacokinetics Assessed by measuring trough levels of everolimus 12 Months Yes
Other Safety Levels of and abnormalities in blood control values 12 Months Yes
Primary Cognitive ability measured by IQ Assessed by Wechsler scales: Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III NL) and Wechsler Intelligence Scale for Children (WISC-III-NL) 12 months No
Secondary Autistic features Assessed by Autism Diagnostic Observation Schedule (ADOS) 12 Months No
Secondary Social and communicational skills Assessed by social responsiveness scale (SRS) and Dutch Children's Communication Checklist (CCC-2-NL) questionnaires 12 Months No
Secondary Working memory and attention, information processing Assessed by Cambridge Neuropsychological Test Automated Battery (CANTAB) 6 and 12 Months No
Secondary Visual-motor integration Assessed by BEERY Visual-Motor Integration (BEERY VMI), grooved pegboard 12 Months No
Secondary Child behavior Assessed by Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) questionnaires 12 Months No
Secondary Executive functioning Assessed by Behavior Rating Inventory of Executive Functioning (BRIEF) questionnaire Dutch version 12 Months No
Secondary Sleeping problems Assessed by Sleep Disturbance Scale for Children (SDSC) questionnaire 12 Months No
Secondary Child health Assessed by Child Health Questionnaire Parent Form (CHQ-PF50) questionnaire 12 Months No
Secondary Sensory related difficulties Assessed by Short Sensory Profile (SSP) questionnaire 12 Months No
Secondary Epilepsy Comparison of epilepsy frequency during month previous to study start and last month of trial participation.
EEG abnormalities
12 Months No
See also
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Completed NCT02201212 - Everolimus for Cancer With TSC1 or TSC2 Mutation Phase 2
Completed NCT01767779 - Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC
Recruiting NCT05104983 - Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study Phase 2
Recruiting NCT02098759 - Long-term, Prospective Study Evaluating Clinical and Molecular Biomarkers of Epileptogenesis in a Genetic Model of Epilepsy - Tuberous Sclerosis Complex N/A
Recruiting NCT03356769 - Aspirin as an add-on Treatment of Refractory Epilepsy in Tuberous Sclerosis Complex Phase 2
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Active, not recruiting NCT04112537 - Dermatologic Patterns of Tuberous Sclerosis Patients and Somatic Mutation Relationship
Active, not recruiting NCT02962414 - Roll-over Study to Collect and Assess Long-term Safety of Everolimus in Patients With TSC and Refractory Seizures Who Have Completed the EXIST-3 Study [CRAD001M2304] and Who Are Benefitting From Continued Treatment Phase 3
Active, not recruiting NCT05495425 - Clinical Study of NPC-12Y Gel in Patients With Skin Lesions Associated With TSC Phase 3
Active, not recruiting NCT05044819 - Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution Phase 4
Completed NCT01929642 - Rapalogues for Autism Phenotype in TSC: A Feasibility Study Phase 2
Recruiting NCT06160310 - Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)

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