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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01253317
Recruitment Status : Completed
First Posted : December 3, 2010
Results First Posted : June 22, 2017
Last Update Posted : June 22, 2017
International Rett Syndrome Foundation
Autism Speaks
Information provided by (Responsible Party):
Mustafa Sahin, Boston Children's Hospital

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.


Condition or disease Intervention/treatment Phase
Rett Syndrome Drug: rhIGF-1 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation With IGF-1
Study Start Date : December 2010
Actual Primary Completion Date : September 2012
Actual Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rett Syndrome
Drug Information available for: Mecasermin

Arm Intervention/treatment
Experimental: 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.
Drug: 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.
Other Name: Mecasermin (brand name Increlex)

Primary Outcome Measures :
  1. Adverse Events [ Time Frame: biweekly during the MAD and every five weeks during the OLE ]
  2. 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. ]

Secondary Outcome Measures :
  1. 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).

  2. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years to 12 Years   (Child)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01253317

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United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children's Hospital
International Rett Syndrome Foundation
Autism Speaks
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Principal Investigator: Mustafa Sahin, MD, PhD Boston Children's Hospital
Additional Information:
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Responsible Party: Mustafa Sahin, Professor in Neurology, Harvard Medical School, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT01253317    
Other Study ID Numbers: 10-08-0403
First Posted: December 3, 2010    Key Record Dates
Results First Posted: June 22, 2017
Last Update Posted: June 22, 2017
Last Verified: June 2017
Keywords provided by Mustafa Sahin, Boston Children's Hospital:
Rett Syndrome
Additional relevant MeSH terms:
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Rett Syndrome
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Growth Substances
Physiological Effects of Drugs