Table 1.
Outcome Measures Used in Prior Published Trials in FXS
| Trial (First author, Year published (reference)) | Design1 | N2 | Measures Used3 | Measures Reliable4 | Measures Change- Sensitive5 | ||
|---|---|---|---|---|---|---|---|
| Behavioral | Cognitive | Biomarker | |||||
| High-dose folate, (Hagerman, 1986 (112)) | DB, PC, XO | 25 | CARS, AutBC | PPVT, TOLD, IQ | ND | None | |
| Methylphenidate, (Hagerman 1988 (113)) | DB, PC, XO | 15 | Conner Scales | ND | Conner | ||
| Folinic acid (Strom 1992 (114)) | DB, PC, XO | 21 | CTRS, CPRS ACTeRS | VABS, PPVT | ND | None | |
| Methylphenidate, Amphetamine salts, (Hagerman 2002 (115)) | OL | 19 | EDR | ND | EDR | ||
| CX516, (Berry-Kravis 2006 (116)) | DB, PC | 48 | ABC, SNAPIV, VAS, CGI, CARS, GARS, ADOS | RBANS, CELF, PLS-4, PPVT, TVPS, W- JMem, IVA, VABS | PPVT, PLS-4, RBANS (LR, LL, DS, SM subtests), W-JMem, SNAPIV, ADOS Comm, CARS, ABC Subscales, VAS Behavior | None | |
| N-acetyl-carnitine (Torrioli 2008 (117)) | DB, PC, XO | 63 | CGI-T, CGI-P | VABS, WISC | ND | CGI-T, CGI-T, VABS | |
| Lithium, (Berry-Kravis 2008 (80)) | OL | 15 | ABC, VAS, CGI | RBANS, PPVT, CFXCPT, NEPSY Tower, NVALT, Card Task, VABS | ERK, Eye Tracking, Auditory Filtering, Autonomic Testing – RSA, HR, HRV | CFXCPT (in concurrent study) | ABC, VAS, CGI, RBANS (LL), VABS-L, ERK |
| Fenobam, (Berry- Kravis 2009 (96)) | OL | 12 | CFXCPT | PPI | PPI (concurrent study) | PPI | |
| Donepezil, (Fung 2012, Kesler 2009, (73,111)) | OL | ABC, CBCL | CNT, HVLT | MRS | |||
| Memantine, (Erickson 2009 (118)) | OL | 6 | ABC, CGI, ADHDRS-IV, SRS | ND | None significant | ||
| Valproic acid, (Torrioli 2010 (119)) | OL | 10 | CTRS, CPRS, CGI, SNAPIV, K-SADS-PL | VABS | FMR1 re- activation | ND | CPRS-R |
| Minocycline, (Paribello 2010 (120)) | OL | 20 | ABC, CGI, VAS | RBANS, PPVT, NVALT | ND | ABC, CGI, VAS, RBANS (LL, SM) | |
| Aripiprazole, (Erickson 2010 (121)) | OL | 15 | ABC, CGI, CY-BOCS | ND | ABC, CY-BOCS, CGI | ||
| Riluzole, (Erickson 2011 (90)) | OL | 6 | CY-BOCS, CGI ADHDRS-IV, ABC, SRS | PPVT | ERK | ND | ADHDRS-IV, ERK |
| AFQ056, (Jacquemont 2011 (76)) | DB, PC, XO | 30 | ABC, RBS, CGI, VAS, SRS | KiTAP, RBANS, PPVT | ERK, Eye Tracking, PPI, FMR1 methylation, FMR1 mRNA | ND | CGI, ABC, RBS, VAS (in fully methylated group) |
| Oxytocin, (Hall 2012 (122)) | DB, PC | 8 | Eye tracking, cortisol, Autonomic Testing – RSA, HR, HRV | ND | Eye tracking, cortisol | ||
| Arbaclofen, (Berry- Kravis 2012 (72)) | DB, PC, XO | 62 | ABC, RBS, VAS, CGI, SRS, CASI, ADHDRS-IV | RBANS, PPVT, VABS, SB5- WM | PPI, APP | ABC-SW, VABS- P/L, CGI, VAS | |
| Acamprosate, (Erickson 2012 (123)) | OL | 12 | ABC, CGI, SRS, CASI, ADHDRS-IV | PPVT, VABS | APP | APP, ABC, CGI, SRS, ADHDRS-IV | |
DB=Double-blind, PC=Placebo-controlled, XO=Crossover, OL=Open label
Number of subjects in trial
Adaptive measures are included in the Cognitive section. Abbreviations for measures as follows: ABC=Aberrant Behavior Checklist-Community Edition (SW=Social Withdrawal Subscale), ACTeRS=ADD-H Comprehensive Teacher’s Rating Scales, ADHDRS-IV=ADHD Rating Scale IV, ADOS=Autism Diagnostic Observation Scale, APP=Amyloid precursor protein, AutBC=Autism Behavior Checklist, Card Task=Card Task Test of Visual Sequential Memory, CARS=Childhood Autism Rating Scale, CASI=Childhood Anxiety Sensitivity Index, CBCL=Child Behavior Checklist, CELF=Clinical Evaluation of Language Skills, CFXCPT=Carolina Project Fragile X Continuous Performance Test, CGI=Clinician Global Impression, CGI-P=Conner Global Index for Parents, CGI-T=Conner Global Index for Teachers, CNT+=Contingency Naming Task, CPRS=Conner Parent Rating Scale, CTRS=Conner Teacher Rating Scale, CY-BOCS =Children’s Yale-Brown Obsessive Compulsive Scale modified for pervasive developmental disorders, EDR=Electrodermal responses, ERK=ERK-related kinase activation rate, GARS=Gillam Autism Rating Scale, HR=Heart Rate, HRV=Heart Rate Variability, HVLT=Hopkins Verbal Learning Test, IVA=Integrated Visual-Auditory CPT, KiTAP=Tests of Attentional Performance for Children, K-SADS PL=Kiddie Schedule for Affective Disorder and Schizophrenia for School Age Children - Present and Lifetime Version, NVALT=Non-Verbal Associative Learning Task, PLS-4=Preschool Language Scale – Version 4, PPI=Prepulse Inhibition, PPVT=Peabody Picture Vocabulary Test, RBANS=Repeatable Battery for the Assessment of Neurological Status (LL=List Learning, SM=Story Memory, DS=Digit Span, LR=List Recall Subtests), RBS=Repetitive Behavior Scale, RSA=Respiratory Sinus Arrythmia, SB5-WM=Stanford-Binet Version 5 Working Memory Index, SNAPIV=Swanson, Nolan, and Pelham Questionaire for ADHD, SRS=Social Responsiveness Scale, TOLD=Test of Language Development, TVPS=Test of Visual Perceptual Skills, VABS=Vineland Adaptive Behavior Scale (P/L=Play and Leisure Subscale), VAS=Visual Analog Scale, W-JMem=Woodcock-Johnson Memory for Words
Reliability not assessed in all trials, data presented includes only those analyzed that had ICC or weighted Kappa>0.8 on test retest
Measures change-sensitive in trial are presented, it must be recognized that lack of change-sensitivity in the absence of a drug effect does not rule out change sensitivity for the measure, change sensitivity may be exaggerated or reported as present when measuring only placebo effect in open-label studies, if just a subtest was change-sensitive-subtest name given in parethesis