A Study of Everolimus in the Treatment of Neurocognitive Problems in Tuberous Sclerosis

NCT01954693 | Unknown Phase 2 DMC

• 2 other identifiers: SPON803-102011-004854-25
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberous Sclerosis

Keywords

Tuberous Sclerosis; Everolimus; Neurocognitive functioning

Outcome Measures

Primary Outcomes (5)

• List Learning test (from the BIRT Memory and Information Processing Battery)

  6 months

• Complex Figure test (from the BIRT Memory and Information Processing Battery)

  6 months

• CANTAB - Stockings of Cambridge (SOC)

  6 months

• CANTAB - Spatial Working Memory (SWM)

  6 months

• Telephone search dual task (from the Test of Everyday Attention)

  6 months

Secondary Outcomes (12)

• CANTAB - Rapid Visual Information Processing Battery (RVIP)

  6 months

• CANTAB - Spatial Span (SSP)

  6 months

• CANTAB - Attentional Set-shifting (IDED)

  6 month

• Verbal Fluency /Controlled Oral Word Association Test (COWAT)

  6 months

• Cancellation task

  6 months

Other Outcomes (2)

• Wechsler Abbreviated Scale of Intelligence (WASI) (4 subtests)

  Eligibility visit

• Edinburgh Handedness Test

  Eligibility visit

Study Arms (2)

Everolimus (RAD001)

EXPERIMENTAL

2x2.5mg daily

Drug: Everolimus (RAD001)

Placebo

PLACEBO COMPARATOR

2x2.5mg daily

Drug: Placebo

Interventions

Placebo DRUG

5mg daily administered for 6 months as two oral 2.5 mg tablets once daily.

Placebo

Everolimus (RAD001) DRUG

5mg daily administered for 6 months as two oral 2.5 mg tablets once daily

Everolimus (RAD001)

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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;
• A score falling on, or below, the 5th percentile (approximately equivalent to -1.5 SD) in one or more of the primary outcome measures:
• 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;
• 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 full recruitment and randomization at baseline. 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.

You may not qualify if:

• 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);
• 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;

Sponsors & Collaborators

• Cardiff University: lead
• Novartis: collaborator

Study Sites (1)

Cardiff University

Cardiff, CF14 4YS, United Kingdom

Location

MeSH Terms

Conditions

Tuberous Sclerosis

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Julian Sampson, Prof

  Cardiff University

  PRINCIPAL INVESTIGATOR

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: Professor

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: October 7, 2013
• Study Start: June 1, 2012
• Primary Completion: August 6, 2018
• Study Completion: August 6, 2018
• Last Updated: January 30, 2018

Record last verified: 2018-01

Locations

GB (1)