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

Each time the patient was seen after the study intervention was initiated, the clinician compared the patient's overall clinical condition to the CGI-S score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment.

The possible range for reported scores is 1-7.

The PGI-S is the parent version of the CGI-S. Parents/caregivers/LAR are asked to rate the severity of their child's symptoms at baseline on a 7-point scale from not at all impaired to the most impaired. The parents/caregivers/LAR will complete the PGI-S at each study visit.

The scores that correspond to each possible grouping are as follows:

1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired.

The possible range for reported scores is 1-7.

As part of each visit after the study intervention was initiated, the parent/caregiver was asked to compare the patient's overall clinical condition to the score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment.

The possible range for reported scores is 1-7.

The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).

The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).

The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).

The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

The Kerr clinical severity scale (Kerr scale) is a quantitative measure of global disease severity. The Kerr scale is a summation of individual items related to Rett syndrome phenotypic characteristics. The items are based on the severity or degree of abnormality of each characteristic on a discrete scale (0, 1, 2) with the highest level corresponding to the most severe or most abnormal presentations.

The possible range of scores is 0-48. The higher the score, the more severe the symptoms.

Remaining subscales of the ADAMS that are not primary outcome measures include: Manic/hyperactive, Depressed mood, General anxiety, Obsessive/compulsive behavior.

The range for each subscale is as follows:

Manic/Hyperactive Behavior: 0-15 Depressed Mood: 0-21 General Anxiety: 0-21 Obsessive/Compulsive Behavior: 0-9

The higher the score for each subscale, the more problematic the behavior.

The MSEL is a standardized developmental test for children ages 3 to 68 months consisting of five subscales: gross motor, fine motor, visual reception, expressive language, and receptive language.

The raw score is reported for each subscale domain. The potential score ranges are as follows:

Visual Reception: 33 items, score range=0-50, Fine Motor: 30 items, score range= 0-49, Receptive Language: 33 items, score range= 0-48, Expressive Language: 28 items, score range= 0-50. The gross motor subscale was not included in this population.

A higher raw score indicates more advanced abilities in that section.

The VABS-II is a survey designed to assess personal and social functioning. Within each domain (Communication, Daily Living Skills, Socialization, and Motor Skills), items can given a score of "2" if the participant successfully performs the activity usually; a "1" if the participant successfully performs the activity sometimes, or needs reminders; a "0" if the participant never performs the activity, and a "DK" if the parent/caregiver is unsure of the participant's ability for an item.

The raw scores in each sub-domain are reported and the ranges for these are as follows: [Communication Domain], Receptive Language=0-40, Expressive Language=0-108, Written Language=0-50; [Daily Living Skills Domain], Personal=0-82, Domestic=0-48, Community=0-88; [Socialization Domain], Interpersonal Relationships=0-76, Play and Leisure Time=0-62, Coping Skills=0-60; [Motor Skills Domain]: Gross Motor Skills=0-80, Fine Motor Skills=0-72.

A higher score indicates more advanced abilities.

The CSBS-DP was designed to measure early communication and symbolic skills in infants and young children (that is, functional communication skills of 6 month to 2 year olds). The CSBS-DP measures skills from three composites: (a) Social (emotion, eye gaze, and communication); (b) Speech (sounds and words); and (c) Symbolic (understanding and object use) and asks about developmental milestones. The data reported are the composite scores for these three categories.

The possible scores for the three composite categories are as follows:

Social Composite = 0-48; Speech Composite = 0-40; Symbolic Composite = 0-51.

A higher score indicates more advanced abilities in that area.

The ABC-C is a global behavior checklist implemented for the measurement of drug and other treatment effects in populations with intellectual disability. Behavior based on 58 items that describe various behavioral problems.

Each item is rated on the parents perceived severity of the behavior. The answer options for each item are:

0 = Not a problem

1. = Problem but slight in degree
2. = Moderately serious problem
3. = Severe in degree

The measure is broken down into the following subscales with individual ranges as follows:

Subscale I (Irritability): 15 items, score range = 0-45 Subscale II (Lethargy): 16 items, score range = 0-48 Subscale III (Stereotypy): 7 items, score range = 0-21 Subscale IV (Hyperactivity): 16 items, score range = 0-48 Subscale V (Inappropriate Speech) was not included in the breakdown because it was not applicable (no participants in the study had verbal language).

Respiratory data was collected using non-invasive respiratory inductance plethysmography from a BioCapture® recording device. BioCapture® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It can be configured with the pediatric chest and abdominal plethysmography bands and the 3 lead ECG signals we plan to use for monitoring cardiac safety throughout the study. Each transducer is placed on the patient independently to provide a customized fit that yields the highest signal quality for each patient irrespective of body shape and proportion. The transducer signals captured by the BioCapture® are transmitted wirelessly to a laptop computer where all signals are displayed in real-time.

The apnea index is given as apneas/hour. Data on apneas greater than or equal to 10 seconds are displayed below. The higher the frequency of apnea, the more severe the breathing abnormality.

The ADAMS is completed by the parent/caregiver/LAR and consists of 29 items which are scored on a 4-point rating scale that combines frequency and severity ratings. The instructions ask the rater to describe the individual's behavior over the last six months on the following scale: "0" if the behavior has not occurred, "1" if the behavior occurs occasionally or is a mild problem, "2" if the behavior occurs quite often or is moderate problem, or "3" if the behavior occurs a lot or is a severe problem.

The Social Avoidance subscale of the ADAMS will be used as a primary outcome measure for this trial. The range for this subscale is 0-21. The higher the subscale score, the more problematic the behavior.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

This scale is used to judge the severity of the subject's disease prior to entry into the study. The clinician will rate the severity of behavioral symptoms at baseline on a 7-point scale from not impaired to the most impaired.

The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired.

The possible range for reported scores is 1-7.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

Each time the patient was seen after the study intervention was initiated, the clinician compared the patient's overall clinical condition to the CGI-S score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment.

The possible range for reported scores is 1-7.

Data was not collected at Visit 1 because participants had not yet been exposed to either intervention.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

The PGI-S is the parent version of the CGI-S. Parents/caregivers/LAR are asked to rate the severity of their child's symptoms at baseline on a 7-point scale from not at all impaired to the most impaired. The parents/caregivers/LAR will complete the PGI-S at each study visit.

The scores that correspond to each possible grouping are as follows:

1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired.

The possible range for reported scores is 1-7.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

As part of each visit after the study intervention was initiated, the parent/caregiver was asked to compare the patient's overall clinical condition to the score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment.

The possible range for reported scores is 1-7.

Data was not collected at visit 1 because participants had not yet been exposed to either intervention.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).

The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).

The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS).

The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

The Kerr clinical severity scale (Kerr scale) is a quantitative measure of global disease severity. The Kerr scale is a summation of individual items related to Rett syndrome phenotypic characteristics. The items are based on the severity or degree of abnormality of each characteristic on a discrete scale (0, 1, 2) with the highest level corresponding to the most severe or most abnormal presentations.

The possible range of scores is 0-48. The higher the score, the more severe the symptoms.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

The RSBQ is a parent-completed measure of abnormal behaviors typically observed in individuals with RTT. Each item, grouped into eight subscales, is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true."

The total sum of each subscale is reported. The higher the score, the more severe the symptoms of that subscale in the participant.

The range for each subscale is as follows:

General Mood: 0-16 Body rocking and expressionless face: 0-14 Hand behaviors: 0-12 Breathing Problems: 0-10 Repetitive Face Movements: 0-8 Night-time behaviors: 0-6 Walking Standing: 0-4

The fear/anxiety subscale was used as a primary outcome measure in this study and results can be found in that section.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

Remaining subscales of the ADAMS that are not primary outcome measures include: Manic/hyperactive, Depressed mood, General anxiety, Obsessive/compulsive behavior.

The range for each subscale is as follows:

Manic/Hyperactive Behavior: 0-15 Depressed Mood: 0-21 General Anxiety: 0-21 Obsessive/Compulsive Behavior: 0-9

The higher the score for each subscale, the more problematic the behavior.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

The MSEL is a standardized developmental test for children ages 3 to 68 months consisting of five subscales: gross motor, fine motor, visual reception, expressive language, and receptive language.

The raw score is reported for each subscale domain. The potential score ranges are as follows:

Visual Reception: 33 items, score range=0-50, Fine Motor: 30 items, score range= 0-49, Receptive Language: 33 items, score range= 0-48, Expressive Language: 28 items, score range= 0-50. The gross motor subscale was not included in this population.

A higher raw score indicates more advanced abilities in that section.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

In some cases, the number of participants analyzed is less than 15 for each group due to subject's inability or unwillingness to complete the testing.

The VABS-II is a survey designed to assess personal and social functioning. Within each domain (Communication, Daily Living Skills, Socialization, and Motor Skills), items can given a score of "2" if the participant successfully performs the activity usually; a "1" if the participant successfully performs the activity sometimes, or needs reminders; a "0" if the participant never performs the activity, and a "DK" if the parent/caregiver is unsure of the participant's ability for an item.

The raw scores in each sub-domain are reported and the ranges for these are as follows: [Communication Domain], Receptive Language=0-40, Expressive Language=0-108, Written Language=0-50; [Daily Living Skills Domain], Personal=0-82, Domestic=0-48, Community=0-88; [Socialization Domain], Interpersonal Relationships=0-76, Play and Leisure Time=0-62, Coping Skills=0-60; [Motor Skills Domain]: Gross Motor Skills=0-80, Fine Motor Skills=0-72.

A higher score indicates more advanced abilities.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

The CSBS-DP was designed to measure early communication and symbolic skills in infants and young children (that is, functional communication skills of 6 month to 2 year olds). The CSBS-DP measures skills from three composites: (a) Social (emotion, eye gaze, and communication); (b) Speech (sounds and words); and (c) Symbolic (understanding and object use) and asks about developmental milestones. The data reported are the composite scores for these three categories.

The possible scores for the three composite categories are as follows:

Social Composite = 0-48; Speech Composite = 0-40; Symbolic Composite = 0-51.

A higher score indicates more advanced abilities in that area.

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

The ABC-C is a global behavior checklist implemented for the measurement of drug and other treatment effects in populations with intellectual disability. Behavior based on 58 items that describe various behavioral problems.

Each item is rated on the parents perceived severity of the behavior. The answer options for each item are:

0 = Not a problem

1. = Problem but slight in degree
2. = Moderately serious problem
3. = Severe in degree

The measure is broken down into the following subscales with individual ranges as follows:

Subscale I (Irritability): 15 items, score range = 0-45 Subscale II (Lethargy): 16 items, score range = 0-48 Subscale III (Stereotypy): 7 items, score range = 0-21 Subscale IV (Hyperactivity): 16 items, score range = 0-48 Subscale V (Inappropriate Speech) was not included in the breakdown because it was not applicable (no participants in the study had verbal language).

In some cases, the number of participants analyzed is less than 15 for each group due to caregiver(s) not completing the forms.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

Respiratory data was collected using non-invasive respiratory inductance plethysmography from a BioCapture® recording device. BioCapture® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It can be configured with the pediatric chest and abdominal plethysmography bands and the 3 lead ECG signals we plan to use for monitoring cardiac safety throughout the study. Each transducer is placed on the patient independently to provide a customized fit that yields the highest signal quality for each patient irrespective of body shape and proportion. The transducer signals captured by the BioCapture® are transmitted wirelessly to a laptop computer where all signals are displayed in real-time.

The apnea index is given as apneas/hour. Data on apneas greater than or equal to 10 seconds are displayed below. The higher the frequency of apnea, the more severe the breathing abnormality.

In some cases, the number of participants analyzed is less than 15 for each group due to inability to complete testing session.

One participant from the "rhIGF-1 First, Then Placebo" group was removed from the study prior to Visit 10, so there is only data for 14 participants included at that time point.

This group includes subjects who had a reported Adverse Event (AE) while they were receiving rhIGF-1 treatment.

This group includes subjects who had a reported Adverse Event (AE) while they were not receiving any treatment. This includes the period between Screening and Baseline, the 20-week washout period between study arms, and the 12-week follow up period after study completion.

Participant was in car accident on way to study visit. No injuries sustained.