Clinical Trial: Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: PHARMACOLOGICAL TREATMENT OF RETT SYNDROME BY STIMULATION OF SYNAPTIC MATURATION WITH IGF-1
Brief 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:
- 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. During PHASE 2, a device called BioRadio® will be used to monitor vital signs in a non-invasive way. This information will be recorded and stored on the accompanying laptop. Before starting PHASE 2, the investigators would like to "beta-test" the BioRadio® in PHASE 1. As such, the investigators may ask you to try using the BioRadio® with your child to test the fit and the performance of the equipment. Should you choose to enroll your child in PHASE 2, the investigators will then ask that your child wear the BioRadio® for two hours, on two consecutive days every f
Detailed Summary:
There are two phases to the trial. Phase 1 is an intensive 6-week pharmacokinetic study which will require 3 inpatient stays and 4 half-day outpatient visits. During in-patient sessions, an IV line will be placed for frequent blood samples. A lumbar puncture will be performed by a physician at the beginning and again at the end of Phase 1. The primary goal of Phase 1 is to determine the safety of IGF-1 therapy for girls with RS. As such, the investigators will ask that you monitor your child's blood sugar levels using a glucometer. Your child's health is our utmost concern and she will be monitored continuously to ensure her safety. At the end of Phase 1, you will have the option of enrolling your daughter in an additional 20 weeks of treatment with IGF-1 during Phase 2 of the trial. The investigators must successfully complete Phase 1 before the investigators can move to the second phase of the trial with a larger number of patients.
The second phase will be double-blinded; meaning neither the families nor the researchers will know which participants are receiving IGF-1. The cross-over design of the trial means each subject will receive 20 weeks of either placebo or IGF-1 and then, after the 6-week washout period, participants will receive another 20 weeks of the alternate treatment. All girls enrolled in Phase 2 will receive 20 weeks of treatment with IGF-1.
Girls enrolled in Phase 2 will be seen monthly for safety monitoring, developmental evaluations and lab work. The investigators will ask caregivers to fill out a number of questionnaires and answer questions regarding their daughter's health, behavior and quality of life. The investigators will also monitor your daughter's heart function (ECG) and the electrical activity in her brain (EEG) four times throughout Phase 2. The BioRadio® is a child-friendly measurem
Sponsor: Walter Kaufmann
Current Primary Outcome:
- respiratory inductance plethysmography [ Time Frame: every five weeks during each 20-week arm ]The primary outcome measure will be the index of autonomic/respiratory dysregulation, using non-invasive respiratory inductance plethysmography. The data for index calculation are derived from a device known as the BioRadio®. The BioRadio® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It can be configured with the pediatric chest and abdominal plethysmography bands and 3 lead ECG signal.
- Electrocardiogram [ Time Frame: every five weeks during each 20-week arm ]The BioRadio® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It will be configured for the pediatric chest with 3 lead ECG signals.
Original Primary Outcome:
- respiratory inductance plethysmography [ Time Frame: every four weeks during each 20-week arm ]The primary outcome measure will be the index of autonomic/respiratory dysregulation, using non-invasive respiratory inductance plethysmography. The data for index calculation are derived from a device known as the BioRadio®. The BioRadio® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It can be configured with the pediatric chest and abdominal plethysmography bands and 3 lead ECG signal.
- Electrocardiogram [ Time Frame: every two weeks during each 20-week arm ]The BioRadio® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It will be configured for the pediatric chest with 3 lead ECG signals.
Current Secondary Outcome:
- Growth Measurements [ Time Frame: every five weeks throughout each 20-week arm ]measuring height, weight, head circumference
- Clinical Assessment [ Time Frame: every five weeks during each 20-week arm ]assess severity of neurological and motor symptoms of Rett Syndrome.
- Clinical Severity Scale [ Time Frame: every five weeks during each 20-week phase ]measures severity of clinical features of Rett Syndrome
- Fundoscopic [ Time Frame: every five weeks during each 20 week arm ]Assesses cranial pressure.
- Tonsillar and Otolaryngological Exam [ Time Frame: every five weeks during each 20 week arm ]Measures tonsillar growth.
- Electroencephalogram [ Time Frame: every five weeks during each 20-week arm ]evaluates changes in epileptiform waves.
- Scoliosis x-ray [ Time Frame: at the beginning and end of each 20-week arm ]determine if degree of scoliosis is affected by medication.
- RNA profiling [ Time Frame: beginning and end of each 20-week arm ]The investigators will perform a genetic test to determine if the RNA profile of subjects is altered by the medication.
- Mullen Scales of Early Learning [ Time Frame: beginning and end of each 20-week arm ]The investigators will administer this test to assess if the medication has an effect on cognition, motor function, and language skills.
- Vineland Adaptive Behavior Scales [ Time Frame: every five weeks during each 20 week arm ]This parental interview will be administered to determine if there is any change in subjects' adaptive behavior skills during the trial.
- Clinical Global Impression Scales [ Time Frame: every five weeks during each 20 week arm ]
- Unified Parkinson Disease Rating Scale [ Time Frame: every five weeks during each 20 week arm ]
- Child Health Questionnaire [ Time Frame: beginning and end of each 20-week arm ]Child quality of life measure.
- Your Health and Well-Being [ Time Frame: beginning and end of each 20-week arm ]Parental quality of life measure.
- Stereotypy Linear Analog Scale [ Time Frame: every five weeks during each 20 week arm ]Evaluates severity of stereotypical hand movements.
- Rett Syndrome Behavior Questionnaire [ Time Frame: every five weeks during each 20 week arm ]
- Aberrant Behavior Checklist [ Time Frame: every five weeks during each 20 week arm ]
- Parent Targeted Symptoms Visual Analog Scales [ Time Frame: Monthly ]Parent or caregiver selected target symptoms (3) measures on linear analog scale for duration of study
Original Secondary Outcome:
- Growth Measurements [ Time Frame: every four weeks throughout each 20-week arm ]measuring height, weight, head circumference
- Clinical Assessment [ Time Frame: every four weeks during each 20-week arm ]assess severity of neurological and motor symptoms of Rett Syndrome.
- Clinical Severity Scale [ Time Frame: every four weeks during each 20-week phase ]measures severity of clinical features of Rett Syndrome
- Fundoscopic [ Time Frame: every four weeks during each 20 week arm ]Assesses cranial pressure.
- Tonsillar and Otolaryngological Exam [ Time Frame: every four weeks during each 20 week arm ]Measures tonsillar growth.
- Electroencephalogram [ Time Frame: every 4 weeks during each 20-week arm ]evaluates changes in epileptiform waves.
- Scoliosis x-ray [ Time Frame: at the beginning and end of each 20-week arm ]determine if degree of scoliosis is affected by medication.
- RNA profiling [ Time Frame: beginning and end of each 20-week arm ]The investigators will perform a genetic test to determine if the RNA profile of subjects is altered by the medication.
- Mullen Scales of Early Learning [ Time Frame: beginning and end of each 20-week arm ]The investigators will administer this test to assess if the medication has an effect on cognition, motor function, and language skills.
- Vineland Adaptive Behavior Scales [ Time Frame: every 4 weeks during each 20 week arm ]This parental interview will be administered to determine if there is any change in subjects' adaptive behavior skills during the trial.
- Clinical Global Impression Scales [ Time Frame: every 4 weeks during each 20 week arm ]
- Modified Ashworth Scale [ Time Frame: every 4 weeks during each 20 week arm ]
- Unified Parkinson Disease Rating Scale [ Time Frame: every 4 weeks during each 20 week arm ]
- Medical Research Council Grading System [ Time Frame: every 4 weeks during each 20 week arm ]Muscle strength scale.
- Child Health Questionnaire [ Time Frame: every 4 weeks during each 20 week arm ]Child quality of life measure.
- Your Health and Well-Being [ Time Frame: every 4 weeks during each 20 week arm ]Parental quality of life measure.
- Stereotypy Linear Analog Scale [ Time Frame: every 4 weeks during each 20 week arm ]Evaluates severity of Rett Syndrome stereotypies.
- Rett Syndrome Behavior Questionnaire [ Time Frame: every 4 weeks during each 20 week arm ]
- Aberrant Behavior Checklist [ Time Frame: every 4 weeks during each 20 week arm ]
- Parent Targeted Symptoms Visual Analog Scales [ Time Frame: Monthly ]Parent or caregiver selected target symptoms (3) measures on linear analog scale for duration of study
Information By: Boston Children’s Hospital
Dates:
Date Received: December 2, 2010
Date Started: December 2010
Date Completion:
Last Updated: January 24, 2013
Last Verified: January 2013
- respiratory inductance plethysmography [ Time Frame: every five weeks during each 20-week arm ]
