Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)
Condition: Rett Syndrome
MeSH terms: Rett Syndrome; Syndrome
Intervention: rhIGF-1
Intervention description: 1) Multiple ascending dose (MAD) period (4 weeks): Subjects will receive escalating twice-daily doses of IGF-1 over 4 weeks (40 µg/kg, 80 µg/kg, 120 µg/kg) and then continue treatment at 120 µg/kg BID for 20 weeks should they choose to enroll in the open-label extension period.
Intervention MeSH terms: Mecasermin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: Female
Minimum age: 2 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: Rett Syndrome; IGF-1; Increlex; Mecasermin; IGF1; MECP2; RTT

Summary:

      The investigators are recruiting children for a research study using a medication known as
      IGF-1 (mecasermin or INCRELEX) to see if it improves the health of children with Rett
      syndrome (RTT). To participate in the study your child must be female, between the ages of 2
      to 12 and have a genetic diagnosis (MECP2 deletion or mutation) of Rett Syndrome. As you may
      know, there is no treatment for this illness. Currently, the standard management of Rett
      syndrome is supportive, which means attempting to prevent complications and treatment of
      symptoms.

      This study involves testing an investigational drug, which means that even though IGF-1 is
      approved by the Food and Drug Administration (FDA) for use in children, it has not been used
      before to treat Rett syndrome specifically. Information from this research will help
      determine whether the drug should be approved by the FDA in the future for the treatment of
      Rett Syndrome.

      There are five major goals to this study:

        1. As one of the features of Rett Syndrome is unstable vital signs, the investigators are
           trying to determine if IGF-1 has any effect on normalizing your child's pulse, blood
           pressure and breathing pattern.

        2. The safety of IGF-1 in children with Rett syndrome. The study personnel will ask you to
           complete a medication diary and side effect reporting form on a regular basis. They will
           assist you in completing this by telephone interviews. Your child will undergo 2 lumbar
           punctures performed at the bedside in the clinical research facility. In addition,
           laboratory tests will be performed throughout the study to evaluate the safety of IGF-1.
           These will be blood tests similar to those provided in routine clinical care. Your child
           will undergo regular non-invasive comprehensive physical examinations including
           neurological and eye examination, tonsil evaluation, electrocardiograms (ECG),
           measurement of height, weight and head circumference.

        3. IGF-1 may improve your child's behavior, communication and speech. In order to measure
           this, the investigators will evaluate your child once during each month of treatment
           with neurodevelopmental assessments and a neurological exam. Investigators will also ask
           you about her behavior and day-to-day functioning through a structured parental
           interview and questionnaires.

        4. We will examine your child's cortical function through use of electroencephalography
           (EEG) in conjunction with presentation of visual and auditory stimuli. EEG is a
           non-invasive way of recording the electrical activity of your child's brain.

        5. Children with Rett Syndrome sometimes experience "flushing" in their cheeks or have
           exceptionally cold hands or feet and/or abnormal perspiration. The Qsensor® is a
           non-invasive device worn on a fabric bracelet that continually measures your child's
           perspiration level and body temperature. We would like to use the Qsensor® to determine
           whether or not IGF-1 improves these symptoms.

           .
    

Eligibility criteria:

        Inclusion Criteria:

          -  female

          -  with RTT (typical or variant) as defined using the internationally agreed 2010
             RettSearch criteria.

          -  genetically defined mutation or deletion of the MECP2 gene.

          -  Girls will have the following prepubertal status: (1) Tanner stage 1 or 2 breast
             development; (2) Tanner stage 1 or 2 pubic hair development; (3) and younger than 12
             years by bone age.

          -  Chronological age must be 2 years or older

        Exclusion Criteria:

          -  prior therapeutic use of IGF-1, growth hormone, Lupron® or sex steroids

          -  allergy to the trial product

          -  co-morbid or chronic illness beyond that known to be associated with Rett Syndrome:
             diabetes mellitus, fatty acid oxidation disorder, chromosomal aneuploidy, syndromes
             associated with high risk of malignancy, current or previous exposure to spinal
             irradiation or history of malignancy.

          -  severe scoliosis (defined as a spinal curve of 70 degrees or more as measured on
             clinical and radiological examination)