Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection)

NCT ID: NCT01253317

Last Updated: 2017-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2013-01-31

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.

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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.

Conditions

Rett Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rhIGF-1

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.

Group Type: EXPERIMENTAL

rhIGF-1

Intervention Type: DRUG

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.

Interventions

rhIGF-1

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.

Intervention Type: DRUG

Other Intervention Names

Mecasermin (brand name Increlex)

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)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

International Rett Syndrome Foundation

OTHER

Sponsor Role: collaborator

Autism Speaks

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mustafa Sahin

Professor in Neurology, Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mustafa Sahin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Boston Children's Hospital

Boston, Massachusetts, United States

Countries

United States

Related Links

http://www.rettsyndrome.org/

International Rett Syndrome Foundation website

http://www.autismspeaks.org/

Autism Speaks website

http://www.ncbi.nlm.nih.gov/pubmed/24623853

PNAS publication of phase 1 IGF-1 trial in RTT

Other Identifiers

10-08-0403

Identifier Type: -

Identifier Source: org_study_id