Trial record 3 of 69 for:    Tuberous Sclerosis

A Study of Everolimus in the Treatment of Neurocognitive Problems in Tuberous Sclerosis (TRON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01954693
Recruitment Status : Active, not recruiting
First Posted : October 7, 2013
Last Update Posted : January 30, 2018
Information provided by (Responsible Party):
Julian Sampson, Cardiff University

Brief Summary:

This is a single centre, two-arm, individually randomised, Phase II, double- blind, placebo-controlled trial of RAD001 (Everolimus) versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis (TSC). The IMP is a licensed medicine in this patient group but for a different target of effect. The current trial is a proof of principle study for memory and executive function outcomes.

Following an eligibility visit, patients will be scheduled for baseline visit and randomization. They will then be followed up for 6 months undergoing both safety and neurocognitive assessments whilst taking either the placebo or study drug.

48 patients aged 16 to 60 years with tuberous sclerosis (TSC) who have IQ > 60 and a significant deficit in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to either RAD001 (Everolimus) or Placebo.

Condition or disease Intervention/treatment Phase
Tuberous Sclerosis Drug: Placebo Drug: Everolimus (RAD001) Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: TRON: A Randomised, Double Blind, Placebo-controlled Study of RAD001 (Everolimus) in the Treatment of Neurocognitive Problems in Tuberous Sclerosis
Study Start Date : June 2012
Estimated Primary Completion Date : August 6, 2018
Estimated Study Completion Date : August 6, 2018

Arm Intervention/treatment
Experimental: Everolimus (RAD001)
2x2.5mg daily
Drug: Everolimus (RAD001)
5mg daily administered for 6 months as two oral 2.5 mg tablets once daily
Placebo Comparator: Placebo
2x2.5mg daily
Drug: Placebo
5mg daily administered for 6 months as two oral 2.5 mg tablets once daily.

Primary Outcome Measures :
  1. List Learning test (from the BIRT Memory and Information Processing Battery) [ Time Frame: 6 months ]
  2. Complex Figure test (from the BIRT Memory and Information Processing Battery) [ Time Frame: 6 months ]
  3. CANTAB - Stockings of Cambridge (SOC) [ Time Frame: 6 months ]
  4. CANTAB - Spatial Working Memory (SWM) [ Time Frame: 6 months ]
  5. Telephone search dual task (from the Test of Everyday Attention) [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. CANTAB - Rapid Visual Information Processing Battery (RVIP) [ Time Frame: 6 months ]
  2. CANTAB - Spatial Span (SSP) [ Time Frame: 6 months ]
  3. CANTAB - Attentional Set-shifting (IDED) [ Time Frame: 6 month ]
  4. Verbal Fluency /Controlled Oral Word Association Test (COWAT) [ Time Frame: 6 months ]
  5. Cancellation task [ Time Frame: 6 months ]
  6. Symptom Checklist 90R (SCL-90R) [ Time Frame: 6 months ]
  7. Quality of Life in Epilepsy (QOLIE) [ Time Frame: 6 months ]
  8. Liverpool Seizure Severity Scale (LSSS) [ Time Frame: 6 months ]
  9. Vineland Adaptive Behavior Scales-II (VABS-II) (survey form) [ Time Frame: 6 months ]
  10. Social Responsiveness Scale - Adult version (SRS-A) [ Time Frame: 6 months ]
  11. Social communication questionnaire (SCQ) [ Time Frame: 6 months ]
  12. National Adult Reading Test (NART) [ Time Frame: 6 months ]

Other Outcome Measures:
  1. Wechsler Abbreviated Scale of Intelligence (WASI) (4 subtests) [ Time Frame: Eligibility visit ]
    Eligibility visit screening measure

  2. Edinburgh Handedness Test [ Time Frame: Eligibility visit ]
    Eligibility visit screening measures

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Definite TSC by current clinical criteria (28);
  2. Male or female aged 16 to 60 yrs;
  3. IQ over 60 by Wechsler Abbreviated Scales of Intelligence (WASI) and able to participate in direct neuropsychological tests;
  4. A score falling on, or below, the 5th percentile (approximately equivalent to -1.5 SD) in one or more of the primary outcome measures:
  5. Calculated GFR > 60ml/min/1.73m2 except in case of renal impairment associated with TSC complicating kidneys, where a calculated GFR should be ≥30ml/min/1.73m2;
  6. INR 1.5 or less (anticoagulation permitted if target INR on stable dose of warfarin or LMW heparin for > 2 weeks at time of randomisation) ;
  7. Adequate liver function as shown by: serum bilirubin less than or equal to 1.5 x ULN, ALT and AST less than or equal to 2.5 x ULN;
  8. If sexually active - negative pregnancy test in females at the time of informed consent, contraception for males and pre-menopausal females on study);
  9. Seizure free or stable seizures as defined by no change in type of AEDs in 6 months prior to full recruitment and randomization at baseline. Doses of drugs may have been changed in the 6 months prior to recruitment;
  10. Hepatitis B surface antigen negative, Hepatitis C antibody negative.
  11. All patients must be able to communicate well with the investigator, to understand and comply with the requirements of the study, understand and sign the written informed consent;
  12. Female patients of childbearing potential must be prepared to use two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening.

Exclusion Criteria:

  1. Prior treatment with an mTOR inhibitor;
  2. Investigational agent <30 days prior to randomisation;
  3. Surgery in last 2 months;
  4. Previous brain neurosurgery;
  5. Significant haematological abnormality i.e. haemoglobin < 8g/dL, platelets <80,000/mm3, absolute neutrophil count < 1000/mm3);
  6. Urine protein/creatinine >0.02g/mmol except in case of renal impairment associated with TSC complication of kidneys, where urine protein/creatinine ratio should be >0.1g/mmol for exclusion;
  7. Serum creatinine > 1.5 x ULN except in case of renal impairment associated with TSC complication of kidneys, where serum creatinine should be >300µmol/L for exclusion;
  8. Uncontrolled hyperlipidaemia (fasting cholesterol > 300mg/dL or >7.75 mmol/L and fasting triglycerides >2.5 x ULN, or diabetes with fasting serum glucose > 1.5 x ULN;
  9. History of myocardial infarction, angina or stroke related to atherosclerosis, or any other significant cardiac disease, HIV seropositivity, organ transplant, malignancy other than squamous or basal cell skin cancer;
  10. lymphangioleiomyomatosis with FEV1 <70% of predicted, or any other restrictive pulmonary disease;
  11. Bleeding diathesis or on oral anti-vitamin K medication other than low dose warfarin;
  12. Pregnancy/lactation;
  13. Live vaccine required during trial;
  14. Use of strong inhibitor of CYP3AE;
  15. Use of strong inducer of CYP3AE except for anti epileptic drugs;
  16. Intercurrent infection at time of randomisation;
  17. Inability to complete study materials (outcome measures) in English;
  18. History of significant trauma-related cognitive deficit;
  19. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (e.g. pancreatic insufficiency);
  20. Known sensitivity to Everolimus or other Rapamycin analogues or to its excipients;
  21. Inability to attend scheduled visits.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01954693

United Kingdom
Cardiff University
Cardiff, United Kingdom, CF14 4YS
Sponsors and Collaborators
Cardiff University
Principal Investigator: Julian Sampson, Prof Cardiff University

Responsible Party: Julian Sampson, Professor, Cardiff University Identifier: NCT01954693     History of Changes
Other Study ID Numbers: SPON803-10
2011-004854-25 ( EudraCT Number )
First Posted: October 7, 2013    Key Record Dates
Last Update Posted: January 30, 2018
Last Verified: January 2018

Keywords provided by Julian Sampson, Cardiff University:
Tuberous Sclerosis
Neurocognitive functioning

Additional relevant MeSH terms:
Tuberous Sclerosis
Pathologic Processes
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
Genetic Diseases, Inborn
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents