Ignite Creation Date:
2025-12-25 @ 12:59 AM
Ignite Modification Date:
2026-02-25 @ 8:11 PM
Study NCT ID:
NCT01954693
Status:
UNKNOWN
Last Update Posted:
2018-01-30
First Post:
2013-09-05
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of Everolimus in the Treatment of Neurocognitive Problems in Tuberous Sclerosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'submissionInfos': [{'resetDate': '2023-12-14', 'releaseDate': '2023-03-06'}], 'estimatedResultsFirstSubmitDate': '2023-03-06'}}, 'conditionBrowseModule': {'meshes': [{'id': 'D014402', 'term': 'Tuberous Sclerosis'}], 'ancestors': [{'id': 'D006222', 'term': 'Hamartoma'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009378', 'term': 'Neoplasms, Multiple Primary'}, {'id': 'D009386', 'term': 'Neoplastic Syndromes, Hereditary'}, {'id': 'D065703', 'term': 'Malformations of Cortical Development, Group I'}, {'id': 'D054220', 'term': 'Malformations of Cortical Development'}, {'id': 'D009421', 'term': 'Nervous System Malformations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D020752', 'term': 'Neurocutaneous Syndromes'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068338', 'term': 'Everolimus'}], 'ancestors': [{'id': 'D020123', 'term': 'Sirolimus'}, {'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 48}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2012-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-01', 'completionDateStruct': {'date': '2018-08-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2018-01-29', 'studyFirstSubmitDate': '2013-09-05', 'studyFirstSubmitQcDate': '2013-10-04', 'lastUpdatePostDateStruct': {'date': '2018-01-30', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2013-10-07', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2018-08-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Wechsler Abbreviated Scale of Intelligence (WASI) (4 subtests)', 'timeFrame': 'Eligibility visit', 'description': 'Eligibility visit screening measure'}, {'measure': 'Edinburgh Handedness Test', 'timeFrame': 'Eligibility visit', 'description': 'Eligibility visit screening measures'}], 'primaryOutcomes': [{'measure': 'List Learning test (from the BIRT Memory and Information Processing Battery)', 'timeFrame': '6 months'}, {'measure': 'Complex Figure test (from the BIRT Memory and Information Processing Battery)', 'timeFrame': '6 months'}, {'measure': 'CANTAB - Stockings of Cambridge (SOC)', 'timeFrame': '6 months'}, {'measure': 'CANTAB - Spatial Working Memory (SWM)', 'timeFrame': '6 months'}, {'measure': 'Telephone search dual task (from the Test of Everyday Attention)', 'timeFrame': '6 months'}], 'secondaryOutcomes': [{'measure': 'CANTAB - Rapid Visual Information Processing Battery (RVIP)', 'timeFrame': '6 months'}, {'measure': 'CANTAB - Spatial Span (SSP)', 'timeFrame': '6 months'}, {'measure': 'CANTAB - Attentional Set-shifting (IDED)', 'timeFrame': '6 month'}, {'measure': 'Verbal Fluency /Controlled Oral Word Association Test (COWAT)', 'timeFrame': '6 months'}, {'measure': 'Cancellation task', 'timeFrame': '6 months'}, {'measure': 'Symptom Checklist 90R (SCL-90R)', 'timeFrame': '6 months'}, {'measure': 'Quality of Life in Epilepsy (QOLIE)', 'timeFrame': '6 months'}, {'measure': 'Liverpool Seizure Severity Scale (LSSS)', 'timeFrame': '6 months'}, {'measure': 'Vineland Adaptive Behavior Scales-II (VABS-II) (survey form)', 'timeFrame': '6 months'}, {'measure': 'Social Responsiveness Scale - Adult version (SRS-A)', 'timeFrame': '6 months'}, {'measure': 'Social communication questionnaire (SCQ)', 'timeFrame': '6 months'}, {'measure': 'National Adult Reading Test (NART)', 'timeFrame': '6 months'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Tuberous Sclerosis', 'Everolimus', 'Neurocognitive functioning'], 'conditions': ['Tuberous Sclerosis']}, 'descriptionModule': {'briefSummary': '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.\n\nFollowing 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.\n\n48 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '60 Years', 'minimumAge': '16 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Definite TSC by current clinical criteria (28);\n2. Male or female aged 16 to 60 yrs;\n3. IQ over 60 by Wechsler Abbreviated Scales of Intelligence (WASI) and able to participate in direct neuropsychological tests;\n4. A score falling on, or below, the 5th percentile (approximately equivalent to -1.5 SD) in one or more of the primary outcome measures:\n5. 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;\n6. 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) ;\n7. 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;\n8. If sexually active - negative pregnancy test in females at the time of informed consent, contraception for males and pre-menopausal females on study);\n9. 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;\n10. Hepatitis B surface antigen negative, Hepatitis C antibody negative.\n11. 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;\n12. 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.\n\nExclusion Criteria:\n\n1. Prior treatment with an mTOR inhibitor;\n2. Investigational agent \\<30 days prior to randomisation;\n3. Surgery in last 2 months;\n4. Previous brain neurosurgery;\n5. Significant haematological abnormality i.e. haemoglobin \\< 8g/dL, platelets \\<80,000/mm3, absolute neutrophil count \\< 1000/mm3);\n6. 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;\n7. 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;\n8. 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;\n9. 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;\n10. lymphangioleiomyomatosis with FEV1 \\<70% of predicted, or any other restrictive pulmonary disease;\n11. Bleeding diathesis or on oral anti-vitamin K medication other than low dose warfarin;\n12. Pregnancy/lactation;\n13. Live vaccine required during trial;\n14. Use of strong inhibitor of CYP3AE;\n15. Use of strong inducer of CYP3AE except for anti epileptic drugs;\n16. Intercurrent infection at time of randomisation;\n17. Inability to complete study materials (outcome measures) in English;\n18. History of significant trauma-related cognitive deficit;\n19. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (e.g. pancreatic insufficiency);\n20. Known sensitivity to Everolimus or other Rapamycin analogues or to its excipients;\n21. Inability to attend scheduled visits.'}, 'identificationModule': {'nctId': 'NCT01954693', 'acronym': 'TRON', 'briefTitle': 'A Study of Everolimus in the Treatment of Neurocognitive Problems in Tuberous Sclerosis', 'organization': {'class': 'OTHER', 'fullName': 'Cardiff University'}, 'officialTitle': 'TRON: A Randomised, Double Blind, Placebo-controlled Study of RAD001 (Everolimus) in the Treatment of Neurocognitive Problems in Tuberous Sclerosis', 'orgStudyIdInfo': {'id': 'SPON803-10'}, 'secondaryIdInfos': [{'id': '2011-004854-25', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Everolimus (RAD001)', 'description': '2x2.5mg daily', 'interventionNames': ['Drug: Everolimus (RAD001)']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': '2x2.5mg daily', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Placebo', 'type': 'DRUG', 'description': '5mg daily administered for 6 months as two oral 2.5 mg tablets once daily.', 'armGroupLabels': ['Placebo']}, {'name': 'Everolimus (RAD001)', 'type': 'DRUG', 'description': '5mg daily administered for 6 months as two oral 2.5 mg tablets once daily', 'armGroupLabels': ['Everolimus (RAD001)']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'CF14 4YS', 'city': 'Cardiff', 'country': 'United Kingdom', 'facility': 'Cardiff University', 'geoPoint': {'lat': 51.48, 'lon': -3.18}}], 'overallOfficials': [{'name': 'Julian Sampson, Prof', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Cardiff University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Cardiff University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Novartis', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Julian Sampson', 'investigatorAffiliation': 'Cardiff University'}}}, 'annotationSection': {'annotationModule': {'unpostedAnnotation': {'unpostedEvents': [{'date': '2023-03-06', 'type': 'RELEASE'}, {'date': '2023-12-14', 'type': 'RESET'}], 'unpostedResponsibleParty': 'Julian Sampson, Professor, Cardiff University'}}}}