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Study to Assess Safety and Efficacy of Fingolimod in Children With Rett Syndrome (FINGORETT)

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.
ClinicalTrials.gov Identifier: NCT02061137
Recruitment Status : Completed
First Posted : February 12, 2014
Last Update Posted : June 15, 2018
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
The Trial Objective is to assess safety and efficacy of oral fingolimod (FTY720) in children older than 6 years with Rett Syndrome. So far there is no established treatment for children with Rett Syndrome. Therefore a positive result in terms of safety and first indications of efficacy would path the way to a phase II clinical study with more patients to further test the hypothesis that fingolimod treatment may slow down the regression of motor and language skills.

Condition or disease Intervention/treatment Phase
Rett's Syndrome Drug: fingolimod (FTY720) Phase 1 Phase 2

Detailed Description:

Rett syndrome is a neurodevelopmental disorder characterized by normal early psychomotor development followed by the loss of psychomotor and acquired purposeful hand skills and the onset of stereotyped movement of the hands and gait disturbance. The gene was discovered in 1999 and the disease was found to be caused by a mutation of the methyl-CpGbinding protein 2 (MeCP2). However, in many ways this clinically peculiar condition remains a mystery, with no clear correlations between the gene mutation and abnormal biological markers, neuropathology and/or unique clinical symptoms and signs.

Rett syndrome is an X-linked (Xq28) dominant postnatal severe neurodevelopmental disorder which is the second most common cause for genetic mental retardation in girls and the first pervasive disorder with a known genetic basis. Its incidence is between 1/10,000-15000 live births. The classical variant is characterized by apparently normal development for the first 6-18 months accompanied usually with early deceleration of head growth, followed by period of regression of motor and language skills, hand stereotypes, seizures, autonomic dysfunction and other neurological and related symptoms.

Repeated observations and experiments of the mouse models in several laboratories led to the appreciation of the role of BDNF in the disease pathophysiology. BDNF is a neurotrophic factor playing a major role in neurogenesis, neuronal survival, differentiation, and maturation during early development as well as in synaptic function and plasticity throughout life. Abnormalities in BDNF homeostasis are believed to contribute to the neurological phenotype and pathophysiology in part of the symptoms in methyl-CpG binding protein 2(Mecp2) null mice that show progressive deficits in its expression during the symptomatic stage.

FTY720 (Gilenya) is an orally active modulator of four of the five sphingosine-1 phosphate(S1P) receptors. FTY720 acts as 'super agonist' on the S1P receptor on thymocytes and lymphocytes, inducing uncoupling/internalization of that receptor.

A local study group (Yves-Alain Barde) found that FTY720 increases the levels of brain derived neurotrophic factor and improves symptoms of mice lacking MeCP2. In addition the volume of the striatum seemed to be higher (4 week old mice were treated in 4 days intervals with 0.1mg/kg body weight intraperitoneally).

Based on these results we intend to perform a phase I clinical,study to assess safety and efficacy of oral fingolimod (FTY720) in children with Rett Syndrome. Children will be included if being older than 6 years of age, fulfilling diagnostic criteria of Rett Syndrome in clinical Stages II -IV and having parents that do agree.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Clinical Study to Assess Safety and Efficacy of Oral Fingolimod (FTY720) in Children With Rett Syndrome.
Study Start Date : August 2013
Actual Primary Completion Date : April 2018
Actual Study Completion Date : April 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rett Syndrome

Arm Intervention/treatment
Experimental: Rett syndrome, fingolimod (FTY720)
0.5 or 0.25mg Fingolimod daily
Drug: fingolimod (FTY720)
0.5 or 0.25 mg fingolimod orally daily for each of 6 patients with rett syndrome for 12 months
Other Name: gilenya, fingolimod, FTY720

Primary Outcome Measures :
  1. Levels of Brain derived neurotrophic factor (BDNF) in blood and cerebrospinal fluid before and under treatment [ Time Frame: change of BDNF measured at Baseline, at first dose, at 6 and at 12 months after start of treatment. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Children fulfilling diagnostic criteria (2001, Hagberg B et al. Eur. J. Paediatr. Neurol. 2002) of Rett Syndrome
  • Stages II -IV Hagberg/ Witt-Engerström (Hagberg B, Witt-Engerström I. Am J Med Genet 1986, Hagberg B. Ment Retard Dev Disabil Res Rev 2002)
  • Patients older than 6 years old (have had their 6th birthday)
  • Written informed consent of parents/ of legal guardian
  • Negative testing for pregnancy
  • Positive confirmation of a MECP2 mutation

Exclusion Criteria:

  • Any uncertainty about diagnosis of Rett Syndrome
  • Patients younger than 6 years old (have not yet had their 6thbirthday)
  • Additional associated neurological diseases such as a brain malformation
  • Patient <15kg body weight at timepoint of screening
  • Patients with negative varicella-zoster virus immunoglobulin G (IgG) antibodies
  • Pregnancy or breastfeeding for girls in childbearing potential age

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 ClinicalTrials.gov identifier (NCT number): NCT02061137

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Department of Neuropediatrics - University Children's Hospital
Basel, Switzerland, 4056
Sponsors and Collaborators
University Hospital, Basel, Switzerland
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Principal Investigator: Ludwig Kappos, Prof. Department of Neurology - University Hospital Basel - Switzerland
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02061137    
Other Study ID Numbers: CFTY720D2201T
First Posted: February 12, 2014    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: June 2018
Keywords provided by University Hospital, Basel, Switzerland:
Rett Syndrome (Mecp2 positive)
Fingolimod (FTY 720)
Brain Atrophy
Additional relevant MeSH terms:
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Rett Syndrome
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Fingolimod Hydrochloride
Sphingosine 1 Phosphate Receptor Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs