dextroamphetamine and Bilateral Headache studies

Dextroamphetamine: The d-form of AMPHETAMINE. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic.
(S)-amphetamine : A 1-phenylpropan-2-amine that has S configuration.

Research Excerpts

Excerpt	Relevance	Reference
" It is the gynecologist (who is more familiar with the condition of sympathetic neural hyperalgesia edema syndrome because it is the most common cause of pelvic pain) who may be the physician to introduce dextroamphetamine sulfate as a treatment since this condition is unknown by many specialists in other fields."	7.80	Dextroamphetamine sulfate, a very effective drug for pelvic pain relieved severe retroorbital stabbing pain in a woman with keratoconus who failed to respond to bilateral corneal implants. ( Check, JH; Cohen, R; DiAntonio, G, 2014)
" It is the gynecologist (who is more familiar with the condition of sympathetic neural hyperalgesia edema syndrome because it is the most common cause of pelvic pain) who may be the physician to introduce dextroamphetamine sulfate as a treatment since this condition is unknown by many specialists in other fields."	3.80	Dextroamphetamine sulfate, a very effective drug for pelvic pain relieved severe retroorbital stabbing pain in a woman with keratoconus who failed to respond to bilateral corneal implants. ( Check, JH; Cohen, R; DiAntonio, G, 2014)
" Safety assessments included adverse events."	2.75	Lisdexamfetamine dimesylate: linear dose-proportionality, low intersubject and intrasubject variability, and safety in an open-label single-dose pharmacokinetic study in healthy adult volunteers. ( Buckwalter, M; Ermer, J; Homolka, R; Martin, P; Purkayastha, J; Roesch, B, 2010)
" Most adverse events were mild to moderate and occurred during the first 4 weeks."	2.73	Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. ( Childress, AC; Findling, RL; Krishnan, S; McGough, JJ, 2008)
"The relative bioavailability of oral lisdexamfetamine dimesylate, a prodrug of d-amphetamine, and active d-amphetamine was assessed in an open-label, single-dose, 3-treatment, 3-period, randomized, crossover study in 18 healthy adult volunteers."	2.73	Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study. ( Krishnan, S; Zhang, Y, 2008)

Research

Studies (16)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Aberrant Behavior Checklist - Community Edition (ABC-C)

Timeframe	Studies, this research(%)	All Research%
pre-1990	8 (50.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	5 (31.25)	29.6817
2010's	3 (18.75)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Check, JH	3
DiAntonio, G	1
Cohen, R	1
Findling, RL	1
Childress, AC	1
Krishnan, S	2
McGough, JJ	1
Rostain, AL	1
Ermer, J	1
Homolka, R	1
Martin, P	1
Buckwalter, M	1
Purkayastha, J	1
Roesch, B	1
YOUNG, JV	1
HAYDON, GB	1
GRAY, CP	1
HECKER, SP	1
LEE, PR	1
Jafri, SH	1
Cook, JW	1
Reed, RR	1
Beebe, DK	1
Boimel, P	1
Katsoff, D	1
Zhang, Y	1
Frye, PE	1
Arnold, LE	2
Lechin, F	1
van der Dijs, B	1
Stunkard, A	1
Rickels, K	1
Hesbacher, P	1
Wender, PH	1
McCloskey, K	1
Snyder, SH	1
Sproule, BC	1
Lewis, RK	1
Hazelrig, CG	1
Fricke, FJ	1
Russell, RO	1
Scanlon, J	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation With Recombinant Human IGF-1(Mecasermin [rDNA] Injection)[NCT01777542]	Phase 2	30 participants (Actual)	Interventional	2013-01-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"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~= Problem but slight in degree~= Moderately serious problem~= 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)." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Anxiety, Depression, and Mood Scale (ADAMS)

Intervention	units on a scale (Median)
	Visit 1 - First Intervention: Subscale I	Visit 3 - First Intervention: Subscale I	Visit 5 - First Intervention: Subscale I	Visit 6 - Second Intervention: Subscale I	Visit 8 - Second Intervention: Subscale I	Visit 10 - Second Intervention: Subscale I	Follow-up: Subscale I (Irritability)	Visit 1 - First Intervention: Subscale II	Visit 3 - First Intervention: Subscale II	Visit 5 - First Intervention: Subscale II	Visit 6 - Second Intervention: Subscale II	Visit 8 - Second Intervention: Subscale II	Visit 10 - Second Intervention: Subscale II	Follow-up: Subscale II (Lethargy)	Visit 1 - First Intervention: Subscale III	Visit 3 - First Intervention: Subscale III	Visit 5 - First Intervention: Subscale III	Visit 6 - Second Intervention: Subscale III	Visit 8 - Second Intervention: Subscale III	Visit 10 - Second Intervention: Subscale III	Follow-up: Subscale III (Stereotypy)	Visit 1 - First Intervention: Subscale IV	Visit 3 - First Intervention: Subscale IV	Visit 5 - First Intervention: Subscale IV	Visit 6 - Second Intervention: Subscale IV	Visit 8 - Second Intervention: Subscale IV	Visit 10 - Second Intervention: Subscale IV	Follow-up: Subscale IV (Hyperactivity)
Placebo First, Then rhIGF-1	9.00	9.00	7.00	7.00	4.00	5.00	3.00	13.00	11.00	9.00	11.00	8.00	6.00	6.00	13.00	10.00	11.00	11.00	10.00	8.00	8.00	13.00	12.00	11.00	11.00	7.00	10.00	9.00
rhIGF-1 First, Then Placebo	6.00	4.00	2.00	4.00	3.00	5.00	2.00	8.00	7.00	6.00	5.00	5.00	4.00	5.00	12.00	10.00	9.00	11.00	9.00	9.00	9.00	8.00	8.00	6.00	7.00	4.00	5.00	5.00

"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." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale

Intervention	units on a scale (Median)
	Visit 1- First Intervention: Manic/Hyperactive	Visit 2- First Intervention: Manic/Hyperactive	Visit 3- First Intervention: Manic/Hyperactive	Visit 4- First Intervention: Manic/Hyperactive	Visit 5- First Intervention: Manic/Hyperactive	Visit 6- Second Intervention: Manic/Hyperactive	Visit 7- Second Intervention: Manic/Hyperactive	Visit 8- Second Intervention: Manic/Hyperactive	Visit 9- Second Intervention: Manic/Hyperactive	Visit 10- First Intervention: Manic/Hyperactive	Follow-up: Manic/Hyperactive Subscale	Visit 1- First Intervention: Depressed Mood	Visit 2- First Intervention: Depressed Mood	Visit 3- First Intervention: Depressed Mood	Visit 4- First Intervention: Depressed Mood	Visit 5- First Intervention: Depressed Mood	Visit 6- Second Intervention: Depressed Mood	Visit 7- Second Intervention: Depressed Mood	Visit 8- Second Intervention: Depressed Mood	Visit 9- Second Intervention: Depressed Mood	Visit 10- Second Intervention: Depressed Mood	Follow-up: Depressed Mood Subscale	Visit 1- First Intervention: General Anxiety	Visit 2- First Intervention: General Anxiety	Visit 3- First Intervention: General Anxiety	Visit 4- First Intervention: General Anxiety	Visit 5- First Intervention: General Anxiety	Visit 6- Second Intervention: General Anxiety	Visit 7- Second Intervention: General Anxiety	Visit 8- Second Intervention: General Anxiety	Visit 9- Second Intervention: General Anxiety	Visit 10- Second Intervention: General Anxiety	Follow-up: General Anxiety Subscale	Visit 1- First Intervention: Obsessive Compulsive	Visit 2- First Intervention: Obsessive Compulsive	Visit 3- First Intervention: Obsessive Compulsive	Visit 4- First Intervention: Obsessive Compulsive	Visit 5- First Intervention: Obsessive Compulsive	Visit 6- Second Intervention: Obsessive Compulsive	Visit 7- Second Intervention: Obsessive Compulsive	Visit 8- Second Intervention: Obsessive Compulsive	Visit 9- Second Intervention: Obsessive Compulsive	Visit 10- First Intervention: Obsessive Compulsive	Follow-up: Obsessive Compulsive Behavior Subscale
Placebo First, Then rhIGF-1	8.00	7.00	7.00	7.00	7.00	8.00	6.50	6.00	6.00	5.00	5.00	2.00	4.00	3.00	2.00	2.00	2.00	3.00	2.00	3.00	2.00	2.00	8.00	6.00	6.00	5.00	5.00	6.00	6.00	6.00	4.00	4.00	5.50	4.00	4.00	4.00	3.00	3.00	3.00	3.00	3.00	3.00	2.00	3.50
rhIGF-1 First, Then Placebo	7.00	7.00	6.00	5.00	4.00	6.00	5.00	5.00	4.00	4.50	5.00	4.00	5.00	3.00	3.00	4.00	4.00	3.00	3.00	2.00	3.00	3.50	6.00	7.00	6.00	5.00	5.00	7.00	5.00	4.00	3.00	4.00	4.00	3.00	4.00	4.00	3.00	3.00	3.00	3.00	3.00	2.00	2.50	3.00

"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." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Clinical Global Impression - Improvement (CGI-I)

Intervention	units on a scale (Median)
	Visit 1 - First Intervention	Visit 2 - First Intervention	Visit 3 - First Intervention	Visit 4 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 7 - Second Intervention	Visit 8 - Second Intervention	Visit 9 - Second Intervention	Visit 10 - Second Intervention	Follow-up
Placebo First, Then rhIGF-1	6.00	5.00	5.00	6.00	5.00	4.00	4.00	4.00	3.00	3.50	4.00
rhIGF-1 First, Then Placebo	4.00	5.00	4.00	4.00	3.00	4.00	4.00	4.00	3.00	3.50	3.00

"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." (NCT01777542)
Timeframe: Every 10 weeks during each of the two 20-week treatment periods

Clinical Global Impression - Severity (CGI-S)

Intervention	units on a scale (Median)
	Visit 3 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 8 - Second Intervention	Visit 10 - Second Intervention
Placebo First, Then rhIGF-1	4.00	4.00	4.00	4.00	4.00
rhIGF-1 First, Then Placebo	4.00	4.00	4.00	4.00	4.00

"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." (NCT01777542)
Timeframe: Every 10 weeks during each of the two 20-week treatment periods

Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP)

Intervention	units on a scale (Median)
	Visit 1 - First Intervention	Visit 3 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 8 - Second Intervention	Visit 10 - Second Intervention
Placebo First, Then rhIGF-1	4.00	4.00	4.00	4.00	4.00	4.00
rhIGF-1 First, Then Placebo	4.00	4.00	4.00	4.00	4.00	4.50

"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." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Kerr Clinical Severity Scale

Intervention	units on a scale (Median)
	Visit 1 - First Intervention: Social	Visit 2: Social Composite Score	Visit 3: Social Composite Score	Visit 4: Social Composite Score	Visit 5: Social Composite Score	Visit 6 - Second Intervention: Social	Visit 7 - Second Intervention: Social	Visit 8 - Second Intervention: Social	Visit 9 - Second Intervention: Social	Visit 10 - Second Intervention: Social	Follow-up: Social Composite Score	Visit 1 - First Intervention: Speech	Visit 2 - First Intervention: Speech	Visit 3 - First Intervention: Speech	Visit 4 - First Intervention: Speech	Visit 5 - First Intervention: Speech	Visit 6 - Second Intervention: Speech	Visit 7 - Second Intervention: Speech	Visit 8 - Second Intervention: Speech	Visit 9 - Second Intervention: Speech	Visit 10 - Second Intervention: Speech	Follow-up: Speech Composite Score	Visit 1 - First Intervention: Symbolic	Visit 2 - First Intervention: Symbolic	Visit 3 - First Intervention: Symbolic	Visit 4 - First Intervention: Symbolic	Visit 5 - First Intervention: Symbolic	Visit 6 - Second Intervention: Symbolic	Visit 7 - Second Intervention: Symbolic	Visit 8 - Second Intervention: Symbolic	Visit 9 - Second Intervention: Symbolic	Visit 10 - Second Intervention: Symbolic	Follow-up: Symbolic Composite Score
Placebo First, Then rhIGF-1	19.00	20.00	18.00	18.00	20.00	18.00	20.00	21.00	21.00	22.50	22.50	4.00	3.00	5.00	5.50	6.50	4.00	4.00	5.00	5.00	5.00	6.00	9.50	10.50	10.50	12.00	11.50	13.00	10.25	11.50	11.50	13.75	14.25
rhIGF-1 First, Then Placebo	22.00	24.00	24.00	24.00	23.00	28.00	25.00	27.00	29.00	27.00	28.00	7.00	5.00	8.00	5.00	8.00	8.50	7.00	6.50	5.00	7.25	6.00	14.00	14.50	15.00	14.00	16.50	18.50	17.00	17.00	18.00	17.00	18.00

"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." (NCT01777542)
Timeframe: At the start and end of each 20-week treatment period

Mullen Scales of Early Learning (MSEL)

Intervention	units on a scale (Median)
	Visit 1 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 10 - Second Intervention
Placebo First, Then rhIGF-1	16.50	15.00	15.00	14.00
rhIGF-1 First, Then Placebo	18.00	18.00	19.00	20.00

"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." (NCT01777542)
Timeframe: At the start and end of each 20-week treatment period

Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1

Intervention	units on a scale (Median)
	Visit 1- First Intervention: Visual Reception	Visit 5- First Intervention: Visual Reception	Visit 6- Second Intervention: Visual Reception	Visit 10: Visual Reception Raw Score	Visit 1- First Intervention: Fine Motor	Visit 5- First Intervention: Fine Motor	Visit 6- Second Intervention: Fine Motor	Visit 10- Second Intervention: Fine Motor	Visit 1- First Intervention: Receptive Language	Visit 5- First Intervention: Receptive Language	Visit 6- Second Intervention: Receptive Language	Visit 10- Second Intervention: Receptive Language	Visit 1- First Intervention: Expressive Language	Visit 5- First Intervention: Expressive Language	Visit 6- Second Intervention: Expressive Language	Visit 10- Second Intervention: Expressive Language
Placebo First, Then rhIGF-1	17.00	26.00	23.00	28.00	10.00	9.00	11.00	9.00	20.00	30.00	31.00	31.00	8.00	9.00	6.00	8.00
rhIGF-1 First, Then Placebo	26.00	39.50	42.00	44.00	7.00	7.00	10.00	8.50	25.50	32.00	38.00	36.50	9.00	8.00	10.00	8.00

"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." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2

Intervention	units on a scale (Median)
	Visit 1 - First Intervention	Visit 2 - First Intervention	Visit 3 - First Intervention	Visit 4 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 7 - Second Intervention	Visit 8 - Second Intervention	Visit 9 - Second Intervention	Visit 10 - Second Intervention	Follow-up
Placebo First, Then rhIGF-1	6.50	4.70	5.65	5.05	4.80	4.95	4.55	5.65	4.15	4.80	5.60
rhIGF-1 First, Then Placebo	8.80	4.80	5.35	5.10	5.15	5.20	4.65	5.00	5.15	5.05	5.08

Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3

Intervention	units on a scale (Median)
	Visit 1 - First Intervention	Visit 2 - First Intervention	Visit 3 - First Intervention	Visit 4 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 7 - Second Intervention	Visit 8 - Second Intervention	Visit 9 - Second Intervention	Visit 10 - Second Intervention	Follow-up
Placebo First, Then rhIGF-1	7.75	4.50	5.85	5.00	5.00	5.35	5.50	5.15	3.80	4.90	5.15
rhIGF-1 First, Then Placebo	6.35	5.25	5.95	5.40	5.45	7.10	5.85	5.00	5.13	4.95	5.20

Parental Global Impression - Improvement (PGI-I)

Intervention	units on a scale (Median)
	Visit 1 - First Intervention	Visit 2 - First Intervention	Visit 3 - First Intervention	Visit 4 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 7 - Second Intervention	Visit 8 - Second Intervention	Visit 9 - Second Intervention	Visit 10 - Second Intervention	Follow-up
Placebo First, Then rhIGF-1	7.85	4.70	5.65	4.15	5.00	6.20	4.80	4.85	4.60	4.13	4.55
rhIGF-1 First, Then Placebo	5.70	5.00	5.20	5.35	5.10	5.35	4.95	5.15	5.25	4.55	5.10

"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." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Parental Global Impression - Severity (PGI-S)

Intervention	units on a scale (Median)
	Visit 2 - First Intervention	Visit 3 - First Intervention	Visit 4 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 7 - Second Intervention	Visit 8 - Second Intervention	Visit 9 - Second Intervention	Visit 10 - Second Intervention	Follow-up
Placebo First, Then rhIGF-1	4.00	3.00	3.00	3.00	4.00	3.00	3.00	3.00	3.00	3.00
rhIGF-1 First, Then Placebo	4.00	4.00	4.00	3.00	3.00	3.00	3.00	3.00	3.00	3.00

"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." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Quantitative Measures of Respiration: Apnea Index

Intervention	units on a scale (Median)
	Visit 1 - First Intervention	Visit 2 - First Intervention	Visit 3 - First Intervention	Visit 4 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 7 - Second Intervention	Visit 8 - Second Intervention	Visit 9 - Second Intervention	Visit 10 - Second Intervention	Follow-up
Placebo First, Then rhIGF-1	4.00	4.00	4.00	4.00	4.00	4.00	4.00	4.00	4.00	4.00	4.00
rhIGF-1 First, Then Placebo	6.00	4.00	4.00	4.00	4.00	4.00	4.00	6.00	6.00	5.00	4.00

"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." (NCT01777542)
Timeframe: Every 10 weeks during each of the two 20-week treatment periods

Rett Syndrome Behavior Questionnaire (RSBQ)

Intervention	Apneas/Hour (Median)
	Visit 1 - First Intervention: Apnea Index	Visit 3 - First Intervention: Apnea Index	Visit 5 - First Intervention: Apnea Index	Visit 6 - Second Intervention: Apnea Index	Visit 8 - Second Intervention: Apnea Index	Visit 10 - Second Intervention: Apnea Index
Placebo First, Then rhIGF-1	7.58	4.80	6.93	7.90	7.28	8.91
rhIGF-1 First, Then Placebo	4.05	3.48	3.07	3.62	5.55	5.56

"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." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale

Intervention	units on a scale (Median)
	Visit 1- First Intervention: General Mood	Visit 2- First Intervention: General Mood	Visit 3- First Intervention: General Mood	Visit 4- First Intervention: General Mood	Visit 5- First Intervention: General Mood	Visit 6- Second Intervention: General Mood	Visit 7- Second Intervention: General Mood	Visit 8- Second Intervention: General Mood	Visit 9- Second Intervention: General Mood	Visit 10- Second Intervention: General Mood	Follow-up: General Mood	Visit 1- First Intervention: Body Rocking	Visit 2- First Intervention: Body Rocking	Visit 3- First Intervention: Body Rocking	Visit 4- First Intervention: Body Rocking	Visit 5- First Intervention: Body Rocking	Visit 6- Second Intervention: Body Rocking	Visit 7- Second Intervention: Body Rocking	Visit 8- Second Intervention: Body Rocking	Visit 9- Second Intervention: Body Rocking	Visit 10- Second Intervention: Body Rocking	Followup: Body Rocking	Visit 1- First Intervention: Hand Behaviors	Visit 2- First Intervention: Hand Behaviors	Visit 3- First Intervention: Hand Behaviors	Visit 4- First Intervention: Hand Behaviors	Visit 5- First Intervention: Hand Behaviors	Visit 6- Second Intervention: Hand Behaviors	Visit 7- Second Intervention: Hand Behaviors	Visit 8- Second Intervention: Hand Behaviors	Visit 9- Second Intervention: Hand Behaviors	Visit 10- Second Intervention: Hand Behaviors	Follow-up: Hand Behaviors	Visit 1- First Intervention: Breathing Problems	Visit 2- First Intervention: Breathing Problems	Visit 3- First Intervention: Breathing Problems	Visit 4- First Intervention: Breathing Problems	Visit 5- First Intervention: Breathing Problems	Visit 6- Second Intervention: Breathing Problems	Visit 7- Second Intervention: Breathing Problems	Visit 8- Second Intervention: Breathing Problems	Visit 9- Second Intervention: Breathing Problems	Visit 10- Second Intervention: Breathing Problems	Follow-up: Breathing Problems	Visit 1- First Intervention: Repetitive Face Movem	Visit 2- First Intervention: Repetitive Face Movem	Visit 3- First Intervention: Repetitive Face Movem	Visit 4- First Intervention: Repetitive Face Movem	Visit 5- First Intervention: Repetitive Face Movem	Visit 6- Second Intervention: Repetitive Face Mov	Visit 7- Second Intervention: Repetitive Face Mov	Visit 8- Second Intervention: Repetitive Face Mov	Visit 9- Second Intervention: Repetitive Face Mov	Visit 10- Second Intervention: Repetitive Face Mov	Follow-up: Repetitive Face Movements	Visit 1- First Intervention: Night time Behaviors	Visit 2- First Intervention: Night time Behaviors	Visit 3- First Intervention: Night time Behaviors	Visit 4- First Intervention: Night time Behaviors	Visit 5- First Intervention: Night time Behaviors	Visit 6- Second Intervention: Night time Behavior	Visit 7- Second Intervention: Night time Behavior	Visit 8- Second Intervention: Night time Behavior
Placebo First, Then rhIGF-1	7.00	5.00	6.00	5.00	5.00	4.00	5.50	5.00	6.00	4.00	5.50	6.00	5.00	5.00	6.00	5.00	4.00	5.00	5.00	4.00	5.00	4.50	8.00	9.00	8.00	8.00	8.00	9.00	8.00	8.00	8.00	7.00	7.50	6.00	4.00	5.00	5.00	5.00	6.00	4.50	6.00	5.00	6.00	5.00	2.00	2.00	3.00	2.00	3.00	3.00	3.00	3.00	3.00	3.00	2.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	1.00
rhIGF-1 First, Then Placebo	4.00	3.00	2.00	2.00	3.00	4.00	2.00	2.00	1.00	2.50	2.00	4.00	4.00	3.00	4.00	4.00	4.00	3.00	4.00	3.00	4.00	4.00	8.00	8.00	8.00	9.00	9.00	8.00	9.00	9.00	7.00	9.00	8.50	4.00	4.00	4.00	5.00	4.00	4.00	3.00	3.00	3.00	4.00	3.00	2.00	2.00	3.00	2.00	2.00	3.00	2.00	2.00	2.00	1.50	2.00	1.00	1.00	0.00	0.00	1.00	1.00	0.00	0.00

"The RSBQ is an informant/parent-completed measure of abnormal behaviors typically observed in individuals with RTT, which is completed by a parent/caregiver/LAR. Each item, grouped into eight domains/factors: General mood, Breathing problems, Body rocking and expressionless face, Hand behaviors, Repetitive face movements, Night-time behaviors, Fear/anxiety and Walking/standing), 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 items in each subscale is reported.~For the fear/anxiety subscale, the sum total could be between 0-8. The higher the sum total score, the greater the frequency of fear/anxiety behaviors." (NCT01777542)
Timeframe: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends

Vineland Adaptive Behavior Scales, Second Edition (VABS-II)

Intervention	units on a scale (Median)
	Visit 1 - First Intervention	Visit 2 - First Intervention	Visit 3 - First Intervention	Visit 4 - First Intervention	Visit 5 - First Intervention	Visit 6 - Second Intervention	Visit 7 - Second Intervention	Visit 8 - Second Intervention	Visit 9 - Second Intervention	Visit 10 - Second Intervention	Follow-up
Placebo First, Then rhIGF-1	4.00	5.00	4.00	4.00	3.00	4.00	4.00	3.00	3.00	4.00	3.50
rhIGF-1 First, Then Placebo	5.00	3.00	3.00	3.00	3.00	4.00	3.00	4.00	3.00	3.00	3.50

"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." (NCT01777542)
Timeframe: At the start and end of each 20-week treatment period

Article	Year
Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. CNS spectrums, 2008, Volume: 13, Issue:7 Topics: Administration, Oral; Appetite; Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetam	2008
Lisdexamfetamine in the treatment of attention-deficit/hyperactivity disorder in adults. Current psychiatry reports, 2009, Volume: 11, Issue:5 Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous Sy	2009
Lisdexamfetamine dimesylate: linear dose-proportionality, low intersubject and intrasubject variability, and safety in an open-label single-dose pharmacokinetic study in healthy adult volunteers. Journal of clinical pharmacology, 2010, Volume: 50, Issue:9 Topics: Adult; Area Under Curve; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nerv	2010
Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study. Journal of clinical pharmacology, 2008, Volume: 48, Issue:3 Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Blood Pressure; Capsules; Cr	2008
Fenfluramine in the treatment of obesity. Lancet (London, England), 1973, Mar-10, Volume: 1, Issue:7802 Topics: Adult; Appetite Depressants; Body Weight; Clinical Trials as Topic; Constipation; Dextroamphetamine;	1973
Levoamphetamine and dextroamphetamine: comparative efficacy in the hyperkinetic syndrome. Assessment by target symptoms. Archives of general psychiatry, 1972, Volume: 27, Issue:6 Topics: Aggression; Amphetamine; Attention; Body Weight; Child; Clinical Trials as Topic; Dextroamphetamine;	1972
Double-blind trial of anorectic agents. The Medical journal of Australia, 1969, Feb-22, Volume: 1, Issue:8 Topics: Adolescent; Adult; Aged; Amphetamine; Appetite Depressants; Clinical Trials as Topic; Dextroamphetam	1969

Article	Year
Dextroamphetamine sulfate, a very effective drug for pelvic pain relieved severe retroorbital stabbing pain in a woman with keratoconus who failed to respond to bilateral corneal implants. Clinical and experimental obstetrics & gynecology, 2014, Volume: 41, Issue:1 Topics: Corneal Transplantation; Dextroamphetamine; Female; Headache; Humans; Keratoconus; Pelvic Pain; Symp	2014
Dextroamphetamine sulfate treatment eradicates long-term chronic severe headaches from temporomandibular joint syndrome--a case that emphasizes the role of the gynecologist in treating headaches in women. Clinical and experimental obstetrics & gynecology, 2016, Volume: 43, Issue:1 Topics: Adult; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Femal	2016
NEPHROPATHY ASSOCIATED WITH THE USE OF ANALGESIC MEDICATIONS. Annals of internal medicine, 1965, Volume: 62 Topics: Acute Kidney Injury; Amobarbital; Analgesics; Analgesics, Non-Narcotic; Anti-Bacterial Agents; Antip	1965
Acute onset of bilateral myoclonus in a 16-year-old female. Journal of the Mississippi State Medical Association, 2004, Volume: 45, Issue:6 Topics: Acetaminophen; Acute Disease; Adolescent; Aspirin; Attention Deficit Disorder with Hyperactivity; Ca	2004
Sympathomimetic amine therapy may improve refractory gastroparesis similar to its effect on chronic pelvic pain--case report. Clinical and experimental obstetrics & gynecology, 2007, Volume: 34, Issue:3 Topics: Adult; Dextroamphetamine; Dopamine Uptake Inhibitors; Edema; Female; Flushing; Gastroparesis; Headac	2007
Persistent amphetamine-induced compulsive rituals: response to pyridoxine(B6). Biological psychiatry, 1981, Volume: 16, Issue:6 Topics: Child; Compulsive Behavior; Dextroamphetamine; Headache; Humans; Male; Pyridoxine; Stereotyped Behav	1981
A new treatment for headache: pathophysiologic considerations. Headache, 1977, Volume: 16, Issue:6 Topics: Adolescent; Adult; Aged; Child; Dextroamphetamine; Female; Headache; Humans; Male; Middle Aged; Prop	1977
Therapy of idiopathic postural hypotension. Archives of internal medicine, 1972, Volume: 129, Issue:6 Topics: Adult; Aged; Amines; Amphetamine; Blood Pressure; Blood Volume; Cheese; Dextroamphetamine; Female; F	1972
Treatment of hyperkinetic child with dextroamphetamine and ephedrine. Pediatrics, 1970, Volume: 46, Issue:6 Topics: Asthma; Dextroamphetamine; Ephedrine; Headache; Humans; Hyperkinesis	1970

Intervention	units on a scale (Median)
	Visit 1 - First Intervention: Receptive	Visit 5 - First Intervention: Receptive	Visit 6 - Second Intervention: Receptive Language	Visit 10 - Second Intervention: Receptive Language	Visit 1 - First Intervention: Expressive	Visit 5 - First Intervention: Expressive	Visit 6 - Second Intervention: Expressive Lang.	Visit 10 - Second Intervention: Expressive Lang.	Visit 1 - First Intervention: Written	Visit 5 - First Intervention: Written	Visit 6: - Second Intervention Written Language	Visit 10 - Second Intervention: Written Language	Visit 1 - First Intervention: Personal	Visit 5 - First Intervention: Personal	Visit 6 - Second Intervention: Personal	Visit 10 - Second Intervention: Personal	Visit 1 - First Intervention: Domestic	Visit 5 - First Intervention: Domestic	Visit 6 - Second Intervention: Domestic	Visit 10 - Second Intervention: Domestic	Visit 1 - First Intervention: Community	Visit 5 - First Intervention: Community	Visit 6 - Second Intervention: Community	Visit 10 - Second Intervention: Community	Visit 1 - First Intervention: Interpersonal Rel.	Visit 5 - First Intervention: Interpersonal Rel.	Visit 6 - Second Intervention: Interpersonal Rel.	Visit 10 - Second Intervention: Interpersonal Rel.	Visit 1 - First Intervention: Play and Leisure	Visit 5 - First Intervention: Play and Leisure	Visit 6 - Second Intervention: Play and Leisure	Visit 10 - Second Intervention: Play and Leisure	Visit 1 - First Intervention: Coping Skills	Visit 5 - First Intervention: Coping Skills	Visit 6 - Second Intervention: Coping Skills	Visit 10 - Second Intervention: Coping Skills	Visit 1 - First Intervention: Gross Motor	Visit 5 - First Intervention: Gross Motor	Visit 6 - Second Intervention: Gross Motor	Visit 10 - Second Intervention: Gross Motor	Visit 1 - First Intervention: Fine Motor	Visit 5 - First Intervention: Fine Motor	Visit 6 - Second Intervention: Fine Motor	Visit 10 - Second Intervention: Fine Motor
Placebo First, Then rhIGF-1	13.00	15.00	18.00	20.00	16.00	17.00	18.00	20.00	0.00	0.00	4.00	6.00	9.00	10.00	9.00	10.00	0.00	0.00	0.00	0.00	0.00	1.00	1.00	2.00	18.00	18.00	19.00	20.00	8.00	11.00	12.00	11.00	3.00	2.00	3.00	4.00	31.00	34.00	27.00	27.00	6.00	6.00	7.00	5.00
rhIGF-1 First, Then Placebo	18.00	21.00	22.00	24.50	18.00	22.00	25.00	24.00	4.00	5.00	7.00	7.00	8.00	9.00	8.50	9.50	0.00	0.00	0.00	0.00	3.00	3.00	5.00	5.00	21.00	22.00	21.00	22.50	13.00	12.00	13.00	12.50	3.00	4.00	6.00	4.50	10.00	10.00	11.50	10.50	2.00	3.00	4.00	4.00

dextroamphetamine and Bilateral Headache