Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)
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.
- 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.
- 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.
- 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.
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation With IGF-1|
- Adverse Events [ Time Frame: biweekly during the MAD and every five weeks during the OLE ]
- Pharmacokinetic (PK) Profile - Areas Under the Curve (AUCt) [ Time Frame: 60 minutes pre-dose and 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0, and 12.0 hours post-dose on days 1, 8, 15 and 29. ]
- Change From Pre-MAD Apnea Index at Post-OLE [ Time Frame: pre-MAD (baseline) to post-OLE (after 20 weeks of IGF-1 treatment) ]Apnea indices were compared from pre-MAD (prior to initiating treatment) to post-OLE (after 20 weeks of IGF-1 therapy). A negative value indicates a reduction in apnea index; representing an improved outcome. Apnea Index is defined as the number of apneas (≥ 10 seconds in length) occuring within one hour. The Apnea Index is calculated by dividing the number of qualifying apneic events by the number of hours in which they occurred. An apnea index greater than or equal to 5 is considered clinically significant by the American Academy of Sleep Medicine (AASM).
- Change in Social Avoidance Subscale Scores on the ADAMS From Pre-OLE to Post-OLE [ Time Frame: Pre-OLE (visit 1) and post-OLE (after 20 weeks of IGF-1 therapy) ]The Anxiety Depression and Mood Scale (ADAMS) is completed by the parent/caregiver and consists of 29 items which are scored on a 4-point rating scale that combines frequency and severity ratings. The Social Avoidance subscale [0 = best; 20 = worst] of the ADAMS is reported as a secondary outcome measure. A negative value indicates a decrease in the Social Avoidance subscale; which represents an improved outcome.
|Study Start Date:||December 2010|
|Study Completion Date:||January 2013|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
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 OLE.
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.
Other Name: Mecasermin (brand name Increlex)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01253317
|United States, Massachusetts|
|Boston Children's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Mustafa Sahin, MD, PhD||Boston Children’s Hospital|