Treatment of Rett Syndrome With Recombinant Human IGF-1

NCT ID: NCT01777542

Last Updated: 2018-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2016-11-30

Brief Summary

Investigators are recruiting children for a clinical trial using the medication recombinant human IGF-1 (a.k.a. mecasermin or INCRELEX) to see if it improves the health of children with Rett syndrome (RTT). While IGF-1 is approved by the Food & Drug Administration (FDA) for certain use in children, it is considered an investigational drug in this trial because it has not previously been used to treat RTT. Information from this study will help determine if IGF-1 effectively treats RTT but will not necessarily lead to FDA approval of IGF-1 as a treatment for RTT.

Detailed Description

Enrolled subjects will complete five study periods: screening, two 20-week long treatment periods, a 28-week break between treatment periods ("washout"), and a follow-up phone call 4 weeks after all treatment ends. Subjects will be chosen at random to receive either IGF-1 or placebo during the first treatment period and then switch to the alternate medication for the second treatment period. Therefore, by completion of the trial, all subjects will have received treatment with IGF-1 for 20 weeks. The study will be double-blinded; meaning, neither subjects' families nor study investigators will know who is receiving IGF-1 or placebo at any time. Treatment must be administered by the caregiver twice daily through subcutaneous (just underneath the skin) injections. Caregivers will be trained by research nurses in how to administer the medication. Participation in this study will last approximately eighteen months.

Throughout the course of the trial, investigators will collect information to assess the effects of IGF-1 and monitor for safety. Families must attend study visits at Boston Children's Hospital a total of seven times (including the screening visit) over the course of 18 months. These visits cannot be completed at any other hospital. Parents will fill out questionnaires and undergo a structured interview reporting on their child's health, behavior, and mood. Subjects will undergo clinical and physical examinations by a study doctor. Non-invasive devices and cameras will also be used to monitor things like breathing, hand movements, heart rate, and body temperature. Blood and urine will be collected for routine laboratory tests to monitor for safety. Investigators will also monitor safety by asking parents to complete a medication diary and side effect reporting form on a regular basis. Between trips to Boston Children's Hospital, parents will complete a set of online questionnaires and undergo a structured interview over the phone.

The cost of travel and lodging during research-related visits to and from the hospital will not be covered by the study. If a condition or illness is identified during the trial (and is determined to be unrelated to study treatments), referrals to outside medical care will be made. Study medications and all research-related materials and services will be provided at no cost to participants. Parking vouchers will be provided for all study-related hospital visits.

The study is investigating 5 potential effects:

1. IGF-1 may improve subjects' behavior, communication and/or mood. In order to measure this, investigators will evaluate subjects every 5 weeks throughout each treatment period with behavioral and psychological assessments. All of the tests used during these evaluations are non-invasive. Investigators will ask parents what their impressions are about their child's behavior and day-to-day activities through a structured parental interview and various questionnaires.

2. Investigators will examine subjects' brain function through use of a brain- monitoring device known as electroencephalography (EEG). The EEG measurements will be taken while investigators present subjects with exercises to stimulate their vision and hearing. EEG is a non-invasive way of recording the electrical activity of a subject's brain by applying a net of monitors (electrodes) to their scalp. Through this method investigators gain insight into how brain processes visual and auditory stimulus.

3. As one of the features of RTT is unstable vital signs, investigators are trying to determine if IGF-1 has any effect on normalizing subjects' heart rate and breathing patterns. To measure this, investigators will ask subjects to wear a non-invasive device that includes three electrocardiogram connectors and two stretchy bands that wrap around her chest and abdomen to measure heart rate and respiratory patterns.

4. The safety of IGF-1 in children with RTT is very important. Investigators will ask parents to complete a medication diary and side effect reporting form on a regular basis. In addition, laboratory tests will be performed every 10 weeks throughout each treatment period to evaluate the safety of IGF-1. These will be blood tests similar to those provided in typical clinical care. Subjects will undergo regular non-invasive comprehensive physical and neurological examinations, tonsil evaluation, electrocardiogram (ECG), echocardiogram, scoliosis x-ray, bone age x-ray, ophthalmological exam, and measurements of height, weight and head circumference.

5. Children with RTT often experience unintended, stereotyped hand movements. The Qsensor® is a non-invasive device worn on a fabric bracelet that continually measures subjects' movement. Investigators will use the Qsensor® to determine whether or not IGF-1 affects the presentation of stereotyped hand movements. As such, investigators will ask subjects to wear the Qsensor® during study visits every 10 weeks throughout each treatment period and occasionally at home.

Conditions

Rett Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Treatment Period 1

One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) , and the other half of subjects will be randomly assigned to receive placebo.

Group Type: ACTIVE_COMPARATOR

Recombinant Human Insulin Growth Factor 1 (rhIGF-1)

Intervention Type: DRUG

Subjects will receive twice daily subcutaneous injections of IGF-1.

Placebo

Intervention Type: DRUG

Subjects will receive twice daily subcutaneous injections of a saline solution (placebo).

Treatment Period 2

Subjects that initially received Recombinant Human Insulin Growth Factor 1 (rhIGF-1) will now receive placebo, and subjects that initially received placebo will now receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1).

Group Type: PLACEBO_COMPARATOR

Recombinant Human Insulin Growth Factor 1 (rhIGF-1)

Intervention Type: DRUG

Subjects will receive twice daily subcutaneous injections of IGF-1.

Placebo

Intervention Type: DRUG

Subjects will receive twice daily subcutaneous injections of a saline solution (placebo).

Interventions

Recombinant Human Insulin Growth Factor 1 (rhIGF-1)

Subjects will receive twice daily subcutaneous injections of IGF-1.

Intervention Type: DRUG

Placebo

Subjects will receive twice daily subcutaneous injections of a saline solution (placebo).

Intervention Type: DRUG

Other Intervention Names

mecasermin [rDNA] injection; Increlex; saline

Eligibility Criteria

Inclusion Criteria

• Diagnosis of "classic" (or "typical") Rett Syndrome
• Genetic documentation of MECP2 mutation
• Subject must be post-regression (Hagberg Stage 2)
• Subject and caregiver's primary language must be English
• Subject must reside in North America (US and Canada)
• Caregiver must have internet access and be able to complete questionnaires online and communicate via email
• Subject is stable on current medications for at least 4 weeks
• Subject's regimen of non-pharmacological interventions (physical therapy, speech therapy, etc.) is stable for at least 90 days

Exclusion Criteria

• Severe scoliosis (curvature >40 degrees)
• Bone-age greater than 11 years
• Cardiomegaly (enlarged heart)
• Tanner stage 2 or higher breast development
• Allergy to IGF-1
• Prior use of IGF-1, growth hormone, or sex steroids

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

International Rett Syndrome Foundation

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mustafa Sahin

Associate Professor of Neurology

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

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Other Identifiers

IRB-P00005610

Identifier Type: -

Identifier Source: org_study_id