Efficacy of RAD001/Everolimus in Autism and NeuroPsychological Deficits in Children With Tuberous Sclerosis Complex

NCT01730209 | Unknown Phase 2 DMC

• 1 other identifier: NL38619.078.11
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tuberous Sclerosis Complex; TSC Related Cognitive Disability; TSC Related Autism; TSC Related Learning Problems

Keywords

Tuberous Sclerosis Complex; TSC; Autism; Learning problems; Everolimus; RAD001; Treatment; Cognition; Intellectual disability

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• Autistic features

  12 Months

• Social and communicational skills

  12 Months

• Working memory and attention, information processing

  6 and 12 Months

• Visual-motor integration

  12 Months

• Child behavior

  12 Months

Other Outcomes (3)

• School level

  12 Months

• Pharmacokinetics

  12 Months

• Safety

  12 Months

Study Arms (2)

Everolimus

EXPERIMENTAL

Everolimus once daily for 1 year, titration to trough levels of 5-10 ng/ml

Drug: Everolimus

Placebo

PLACEBO COMPARATOR

Placebo treatment for 1 year. Tablets will be identical to everolimus tablets.

Drug: Placebo

Interventions

Everolimus DRUG

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

Also known as: RAD001, Votubia

Everolimus

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 4 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• Hepatic dysfunction
• Surgery \<6wk
• 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)

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Utrecht University: collaborator

Study Sites (1)

Erasmus Medical Center

Rotterdam, Netherlands

RECRUITING

Related Publications (1)

• Overwater IE, Rietman AB, Mous SE, Bindels-de Heus K, Rizopoulos D, Ten Hoopen LW, van der Vaart T, Jansen FE, Elgersma Y, Moll HA, de Wit MY; ENCORE Expertise Centre for Neurodevelopmental Disorders. A randomized controlled trial with everolimus for IQ and autism in tuberous sclerosis complex. Neurology. 2019 Jul 9;93(2):e200-e209. doi: 10.1212/WNL.0000000000007749. Epub 2019 Jun 19.

  PMID: 31217257 DERIVED

MeSH Terms

Conditions

Tuberous Sclerosis; Autistic Disorder; Intellectual Disability

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• M.C.Y. de Wit, MD. PhD.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

M.C.Y. de Wit, MD. PhD.

CONTACT

+31 10 703 6956; tubereuzesclerose@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Neurologist

Study Record Dates

• First Submitted: October 26, 2012
• First Posted: November 21, 2012
• Study Start: November 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2016
• Last Updated: May 5, 2015

Record last verified: 2015-05

Locations

NL (1)