Treatment of Rett Syndrome With Recombinant Human IGF-1
Condition: Rett Syndrome
MeSH terms: Rett Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      Investigators are recruiting children for a clinical trial using the medication recombinant
      human IGF-1 (a.k.a. mecasermin or INCRELEX) to see if it improves the health of children with
      Rett syndrome (RTT). While IGF-1 is approved by the Food & Drug Administration (FDA) for
      certain use in children, it is considered an investigational drug in this trial because it
      has not previously been used to treat RTT. Information from this study will help determine if
      IGF-1 effectively treats RTT but will not necessarily lead to FDA approval of IGF-1 as a
      treatment for RTT.
    

Detailed description: 
      Enrolled subjects will complete five study periods: screening, two 20-week long treatment
      periods, a 28-week break between treatment periods ("washout"), and a follow-up phone call 4
      weeks after all treatment ends. Subjects will be chosen at random to receive either IGF-1 or
      placebo during the first treatment period and then switch to the alternate medication for the
      second treatment period. Therefore, by completion of the trial, all subjects will have
      received treatment with IGF-1 for 20 weeks. The study will be double-blinded; meaning,
      neither subjects' families nor study investigators will know who is receiving IGF-1 or
      placebo at any time. Treatment must be administered by the caregiver twice daily through
      subcutaneous (just underneath the skin) injections. Caregivers will be trained by research
      nurses in how to administer the medication. Participation in this study will last
      approximately eighteen months.

      Throughout the course of the trial, investigators will collect information to assess the
      effects of IGF-1 and monitor for safety. Families must attend study visits at Boston
      Children's Hospital a total of seven times (including the screening visit) over the course of
      18 months. These visits cannot be completed at any other hospital. Parents will fill out
      questionnaires and undergo a structured interview reporting on their child's health,
      behavior, and mood. Subjects will undergo clinical and physical examinations by a study
      doctor. Non-invasive devices and cameras will also be used to monitor things like breathing,
      hand movements, heart rate, and body temperature. Blood and urine will be collected for
      routine laboratory tests to monitor for safety. Investigators will also monitor safety by
      asking parents to complete a medication diary and side effect reporting form on a regular
      basis. Between trips to Boston Children's Hospital, parents will complete a set of online
      questionnaires and undergo a structured interview over the phone.

      The cost of travel and lodging during research-related visits to and from the hospital will
      not be covered by the study. If a condition or illness is identified during the trial (and is
      determined to be unrelated to study treatments), referrals to outside medical care will be
      made. Study medications and all research-related materials and services will be provided at
      no cost to participants. Parking vouchers will be provided for all study-related hospital
      visits.

      The study is investigating 5 potential effects:

        1. IGF-1 may improve subjects' behavior, communication and/or mood. In order to measure
           this, investigators will evaluate subjects every 5 weeks throughout each treatment
           period with behavioral and psychological assessments. All of the tests used during these
           evaluations are non-invasive. Investigators will ask parents what their impressions are
           about their child's behavior and day-to-day activities through a structured parental
           interview and various questionnaires.

        2. Investigators will examine subjects' brain function through use of a brain- monitoring
           device known as electroencephalography (EEG). The EEG measurements will be taken while
           investigators present subjects with exercises to stimulate their vision and hearing. EEG
           is a non-invasive way of recording the electrical activity of a subject's brain by
           applying a net of monitors (electrodes) to their scalp. Through this method
           investigators gain insight into how brain processes visual and auditory stimulus.

        3. As one of the features of RTT is unstable vital signs, investigators are trying to
           determine if IGF-1 has any effect on normalizing subjects' heart rate and breathing
           patterns. To measure this, investigators will ask subjects to wear a non-invasive device
           that includes three electrocardiogram connectors and two stretchy bands that wrap around
           her chest and abdomen to measure heart rate and respiratory patterns.

        4. The safety of IGF-1 in children with RTT is very important. Investigators will ask
           parents to complete a medication diary and side effect reporting form on a regular
           basis. In addition, laboratory tests will be performed every 10 weeks throughout each
           treatment period to evaluate the safety of IGF-1. These will be blood tests similar to
           those provided in typical clinical care. Subjects will undergo regular non-invasive
           comprehensive physical and neurological examinations, tonsil evaluation,
           electrocardiogram (ECG), echocardiogram, scoliosis x-ray, bone age x-ray,
           ophthalmological exam, and measurements of height, weight and head circumference.

        5. Children with RTT often experience unintended, stereotyped hand movements. The Qsensor®
           is a non-invasive device worn on a fabric bracelet that continually measures subjects'
           movement. Investigators will use the Qsensor® to determine whether or not IGF-1 affects
           the presentation of stereotyped hand movements. As such, investigators will ask subjects
           to wear the Qsensor® during study visits every 10 weeks throughout each treatment period
           and occasionally at home.
    

Intervention name(s): Recombinant Human Insulin Growth Factor 1 (rhIGF-1); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subjects will receive twice daily subcutaneous injections of IGF-1.; Subjects will receive twice daily subcutaneous injections of a saline solution (placebo).
Other intervention name(s): mecasermin [rDNA] injection; Increlex; saline
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Mitogens; Mecasermin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Rett syndrome; RTT; IGF-1; autism spectrum disorder