Clinical trial NCT01253317: Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)
Official title: Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation With IGF-1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rett Syndrome
Keywords: Rett Syndrome
IGF-1
Increlex
Mecasermin
IGF1
MECP2
RTT
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: International Rett Syndrome Foundation
name: Autism Speaks
First posted: 2010-12-03
Enrollment: 12
Sex: FEMALE
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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:

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.

   .

Detailed description: There are two treatment periods in the trial. The multiple ascending dose (MAD) period is an intensive 4-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 the MAD. The primary goal of the MAD is to determine the safety of IGF-1 therapy for girls with RTT. As such, the investigators will ask that you monitor your child's blood sugar levels using a glucometer. At the end of the MAD, you will have the option of enrolling your daughter in an additional 20 weeks of open-label IGF-1 treatment.

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)

Primary outcomes:
measure: Adverse Events
timeFrame: biweekly during the MAD and every five weeks during the OLE
measure: Pharmacokinetic (PK) Profile - Areas Under the Curve (AUCt)
timeFrame: 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.
Secondary outcomes:
measure: Change From Pre-MAD Apnea Index at Post-OLE
timeFrame: pre-MAD (baseline) to post-OLE (after 20 weeks of IGF-1 treatment)
measure: Change in Social Avoidance Subscale Scores on the ADAMS From Pre-OLE to Post-OLE
timeFrame: Pre-OLE (visit 1) and post-OLE (after 20 weeks of IGF-1 therapy)
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
References: