Trial record 2 of 17 for:    Open Studies | "Tuberous Sclerosis"

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

This study is currently recruiting participants.
Verified September 2013 by Cardiff University
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Julian Sampson, Cardiff University
ClinicalTrials.gov Identifier:
NCT01954693
First received: September 5, 2013
Last updated: October 4, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Tuberous Sclerosis
Drug: Placebo
Drug: Everolimus (RAD001)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Cardiff University:

Primary Outcome Measures:
  • List Learning test (from the BIRT Memory and Information Processing Battery) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Complex Figure test (from the BIRT Memory and Information Processing Battery) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • CANTAB - Stockings of Cambridge (SOC) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • CANTAB - Spatial Working Memory (SWM) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Telephone search dual task (from the Test of Everyday Attention) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • CANTAB - Rapid Visual Information Processing Battery (RVIP) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • CANTAB - Spatial Span (SSP) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • CANTAB - Attentional Set-shifting (IDED) [ Time Frame: 6 month ] [ Designated as safety issue: No ]
  • Verbal Fluency /Controlled Oral Word Association Test (COWAT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Cancellation task [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Symptom Checklist 90R (SCL-90R) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Quality of Life in Epilepsy (QOLIE) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Liverpool Seizure Severity Scale (LSSS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Vineland Adaptive Behavior Scales-II (VABS-II) (survey form) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Social Responsiveness Scale - Adult version (SRS-A) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Social communication questionnaire (SCQ) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • National Adult Reading Test (NART) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Wechsler Abbreviated Scale of Intelligence (WASI) (4 subtests) [ Time Frame: Eligibility visit ] [ Designated as safety issue: No ]
    Eligibility visit screening measure

  • Edinburgh Handedness Test [ Time Frame: Eligibility visit ] [ Designated as safety issue: No ]
    Eligibility visit screening measures


Estimated Enrollment: 48
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Definite TSC by current clinical criteria (28);
  • Male or female aged 16 to 60 yrs;
  • IQ over 60 by Wechsler Abbreviated Scales of Intelligence (WASI) and able to participate in direct neuropsychological tests;
  • Deficit of -2S.D. or more below normal population mean on a primary outcome measure;
  • Calculated GFR > 60ml/min/1.73m2;
  • 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) ;
  • 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;
  • If sexually active - negative pregnancy test in females at the time of informed consent, contraception for males and pre-menopausal females on study);
  • Seizure free or stable seizures as defined by no change in type of AEDs in 6 months prior to recruitment. Doses of drugs may have been changed in the 6 months prior to recruitment;
  • Hepatitis B surface antigen negative, Hepatitis C antibody negative.
  • 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;
  • 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:

  • Prior treatment with an mTOR inhibitor;
  • Investigational agent <30 days prior to randomisation;
  • Surgery in last 2 months;
  • Previous brain neurosurgery;
  • Significant haematological abnormality i.e. haemoglobin < 8g/dL, platelets <80,000/mm3, absolute neutrophil count < 1000/mm3);
  • Urine protein/creatinine >0.02g/mmol;
  • Serum creatinine > 1.5 x ULN;
  • 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;
  • 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;
  • lymphangioleiomyomatosis with FEV1 <70% of predicted, or any other restrictive pulmonary disease;
  • Bleeding diathesis or on oral anti-vitamin K medication other than low dose warfarin;
  • Pregnancy/lactation;
  • Live vaccine required during trial;
  • Use of strong inhibitor of CYP3AE;
  • Use of strong inducer of CYP3AE except for anti epileptic drugs;
  • Intercurrent infection at time of randomisation;
  • Inability to complete study materials (outcome measures) in English;
  • History of significant trauma-related cognitive deficit;
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (e.g. pancreatic insufficiency);
  • Known sensitivity to Everolimus or other Rapamycin analogues or to its excipients;
  • Inability to attend scheduled visits.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01954693

Contacts
Contact: Julian Sampson, Prof sampson@cardiff.ac.uk

Locations
United Kingdom
Cardiff University Recruiting
Cardiff, United Kingdom, CF14 4YS
Contact: Julian Sampson, Prof       sampson@cardiff.ac.uk   
Principal Investigator: Julian Sampson, Prof         
Sponsors and Collaborators
Cardiff University
Novartis
Investigators
Principal Investigator: Julian Sampson, Prof Cardiff University
  More Information

No publications provided

Responsible Party: Julian Sampson, Professor, Cardiff University
ClinicalTrials.gov Identifier: NCT01954693     History of Changes
Other Study ID Numbers: SPON803-10, 2011-004854-25
Study First Received: September 5, 2013
Last Updated: October 4, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Cardiff University:
Tuberous Sclerosis
Everolimus
Neurocognitive functioning

Additional relevant MeSH terms:
Tuberous Sclerosis
Sclerosis
Pathologic Processes
Hamartoma
Neoplasms
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014