Clinical trial NCT01777542: Treatment of Rett Syndrome With Recombinant Human IGF-1
Official title: Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation With Recombinant Human IGF-1(Mecasermin [rDNA] Injection)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rett Syndrome
Keywords: Rett syndrome
RTT
IGF-1
autism spectrum disorder
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: International Rett Syndrome Foundation
First posted: 2013-01-29
Enrollment: 30
Sex: FEMALE
Minimum age (years): 2
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of "classic" (or "typical") Rett Syndrome
* Genetic documentation of MECP2 mutation
* Subject must be post-regression (Hagberg Stage 2)
* Subject and caregiver's primary language must be English
* Subject must reside in North America (US and Canada)
* Caregiver must have internet access and be able to complete questionnaires online and communicate via email
* Subject is stable on current medications for at least 4 weeks
* Subject's regimen of non-pharmacological interventions (physical therapy, speech therapy, etc.) is stable for at least 90 days

Exclusion Criteria:

* Severe scoliosis (curvature \>40 degrees)
* Bone-age greater than 11 years
* Cardiomegaly (enlarged heart)
* Tanner stage 2 or higher breast development
* Allergy to IGF-1
* Prior use of IGF-1, growth hormone, or sex steroids

Primary outcomes:
measure: Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Clinical Global Impression - Severity (CGI-S)
timeFrame: Every 10 weeks during each of the two 20-week treatment periods
measure: Clinical Global Impression - Improvement (CGI-I)
timeFrame: Every 10 weeks during each of the two 20-week treatment periods
measure: Parental Global Impression - Severity (PGI-S)
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Parental Global Impression - Improvement (PGI-I)
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Kerr Clinical Severity Scale
timeFrame: At the start and end of each 20-week treatment period
Secondary outcomes:
measure: Rett Syndrome Behavior Questionnaire (RSBQ)
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Anxiety, Depression, and Mood Scale (ADAMS)
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Mullen Scales of Early Learning (MSEL)
timeFrame: At the start and end of each 20-week treatment period
measure: Vineland Adaptive Behavior Scales, Second Edition (VABS-II)
timeFrame: At the start and end of each 20-week treatment period
measure: Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP)
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Aberrant Behavior Checklist - Community Edition (ABC-C)
timeFrame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
measure: Quantitative Measures of Respiration: Apnea Index
timeFrame: Every 10 weeks during each of the two 20-week treatment periods
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Mustafa Sahin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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