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Tuberous Sclerosis ComplexPhase 2/3RAPITNCT01730209

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

A Phase 2/3 study testing Everolimus in people with Tuberous Sclerosis Complex and TSC Related Cognitive Disability, run by Erasmus Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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. Read more about this study

Who is it for?
Ages 4 to 15 years
What is being tested?
Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteNetherlands
Study dates
Nov 2012to Nov 2016
Phase
Phase 2/3
Are there results?
None posted in the registry

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 4 to 15 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 21Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

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

+31 10 703 6956

tubereuzesclerose@erasmusmc.nl

Netherlands1 site, 1 recruiting

  • Erasmus Medical Center

    Rotterdam

    M.C.Y. de Wit, MD. PhD., +31 10 703 6956, tubereuzesclerose@erasmusmc.nl

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

    Recruiting

Other trials in Netherlands

About this study

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.

Read the detailed 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.

Being tested
Everolimus, Placebo
Keywords
Tuberous Sclerosis Complex, TSC, Autism, Learning problems, Everolimus, RAD001, Treatment, Cognition, Intellectual disability
Medical subject headings
Tuberous Sclerosis, Autistic Disorder, Intellectual Disability

What participants receive

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

  • EverolimusDrug

    Also called RAD001, Votubia

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

  • PlaceboDrug

Study groups in NCT01730209
Study groupRoleWhat they receive
EverolimusExperimentalEverolimus once daily for 1 year, titration to trough levels of 5-10 ng/ml
Receives: Drug: Everolimus
PlaceboPlacebo comparatorPlacebo treatment for 1 year. Tablets will be identical to everolimus tablets.
Receives: Drug: Placebo

What is being measured

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

  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)

    Measured: 12 months

Secondary outcomes (10)

  1. Autistic features

    Assessed by Autism Diagnostic Observation Schedule (ADOS)

    Measured: 12 Months

  2. Social and communicational skills

    Assessed by social responsiveness scale (SRS) and Dutch Children's Communication Checklist (CCC-2-NL) questionnaires

    Measured: 12 Months

  3. Working memory and attention, information processing

    Assessed by Cambridge Neuropsychological Test Automated Battery (CANTAB)

    Measured: 6 and 12 Months

  4. Visual-motor integration

    Assessed by BEERY Visual-Motor Integration (BEERY VMI), grooved pegboard

    Measured: 12 Months

  5. Child behavior

    Assessed by Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) questionnaires

    Measured: 12 Months

  6. Executive functioning

    Assessed by Behavior Rating Inventory of Executive Functioning (BRIEF) questionnaire Dutch version

    Measured: 12 Months

  7. Sleeping problems

    Assessed by Sleep Disturbance Scale for Children (SDSC) questionnaire

    Measured: 12 Months

  8. Child health

    Assessed by Child Health Questionnaire Parent Form (CHQ-PF50) questionnaire

    Measured: 12 Months

  9. Sensory related difficulties

    Assessed by Short Sensory Profile (SSP) questionnaire

    Measured: 12 Months

  10. Epilepsy

    Comparison of epilepsy frequency during month previous to study start and last month of trial participation.

    EEG abnormalities

    Measured: 12 Months

Timeline

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

  1. First posted21 Nov 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionNov 2015 (estimated)
  4. Study completionNov 2016 (estimated)

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01730209
Sponsor's protocol ID
NL38619.078.11
Acronym
RAPIT
Status last verified
May 2015
First submitted
26 Oct 2012
Last updated
5 May 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31217257

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Everolimus in people with Tuberous Sclerosis Complex and TSC Related Cognitive Disability, run by Erasmus Medical Center at 1 site in Netherlands.

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 4 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: status not confirmed, as of the sponsor's last update on 5 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Results are not available in the source record.

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

Contact M.C.Y. de Wit, MD. PhD. (+31 10 703 6956, tubereuzesclerose@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cognitive ability measured by IQ (time frame: 12 months). 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 NCT01730209, 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 5 May 2015.

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