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Table 1 Double-blind, placebo-controlled treatment studies of individuals with fragile X

From: Updated report on tools to measure outcomes of clinical trials in fragile X syndrome

FDA register number Compound Mechanism Cohort (years) Sample size Outcomes measured (OM) Phase/sponsor Results/publications
      Primary1 Secondary2   
   14/22, 64%       
NCT00788073 Arbaclofen (STX209) GABA-B agonist 6–50 63 ABC-C_I ABC-CFX, CGI-S, CGI-I, Vineland-II, SRS, RBANS, SB5, PPVT II/Seaside OM:1 not met, 2↓ABC-CFX-SA [112]
NCT01282268 Arbaclofen GABA-B agonist 12–50 125 ABC-CFX_SA CGI-S, CGI-I, Vineland-II, ADHD-RS, SB5, PSI, CSHQ III/Seaside OM:1 not met [46]
NCT01325220 Arbaclofen GABA-B agonist 5–11 172 ABC-CFX_SA CGI-S, CGI-I, Vineland-II, ADHD-RS, SB5, PSI, CSHQ III/Seaside OM:1 not met, 2↓ABC-CFX-I, ↓PSI [46, 113]
NCT01725152 Ganaxolone GABA-A agonist 6–17 60 CGI-I ABC-CFX, ADAMS, PPI, KiTAP, ERP, ET, SNAP-IV, PARS II/Marinus Pending
NCT02126995 Metadoxine GABA transporter 14–50 62 ADHD-RS ABC-CFX, CGI-S, CGI-I, Vineland-II, SRS, KiTAP, ERP, ET, PARS II/Alcobra OM:1 not met, 2↑Vineland II DL [44, 64]
NCT00718341 Mavoglurant (AFQ056) mGluR5 antagonist 18–35 30 ABC-C_T ABC-CFX, CGI-S, CGI-I, SRS, KiTAP, ET, VAS, RBANS.. II/Novartis OM:1 not met,2 ↓ABC-C_T (n=7 FM) [261]
NCT01253629 Mavoglurant mGluR5 antagonist 18–45 175 ABC-C_T ABC-C, CGI-S, CGI-I, SRS, KiTAP IIb/Novartis OM:1 & 2 not met, tolerated well [9]
NCT01357239 Mavoglurant mGluR5 antagonist 12–17 139 ABC-C_T ABC-C, CGI-S, CGI-I, SRS, KiTAP IIb/Novartis OM:1 & 2 not met, tolerated well [9]
NCT01015430 Basimglurant (RO4917523) mGluR5 antagonist 18–50 40 Safety, PK ABC-C, ADAMS, CGI-S, CGI-I, KiTAP, ET, VAS, RBANS IIa/Roche Not in public domain
NCT01517698 Basimglurant mGluR5 antagonist 14–40 185 ADAMS_T ABC-C, ADAMS, CGI-S, CGI-I, WISC-IV, CBI-M IIb/Roche Not in public domain
NCT01750957 Basimglurant mGluR5 antagonist 5–13 180 Safety PK, ABC-C, ADAMS, CGI-S, CGI-I, WISC-IV, CBI-M IIb/Roche Not in public domain
NCT01911455 Acamprosate GABA/Glutamate 5–23 48 ABC-C_SW CGI-S, CGI-I, VAS, ABC, PARS, ADAMS, CSQ, ELS, SRS II/III Cinn Child Pending
NCT01894958 Trofinetide IGF-1 analog 14–40 70 Safety CGI-S, CGI-I, ABC-CFX, SRS, FXS scale, VAS-P/C, KiTAP II/Neuren OM: 1Tolerated well, 2-several improved [63]
NCT00054730 CX516 Ampakine 18+ 49 Memory CGI-I, multiple Z scores, SNAP-IV II/Cortex OM: 1 Tolerated well,2↑CGI-I in a subset [40]
NCT01053156 Minocycline MMP-9 3–16 66 CGI-I,VAS VAS-mb, ABC-C, Vineland-II, EVT-2 II/UC Davis OM:1 ↑CGI-I, 2↑VAS, ↓MMP-9; [87]
NCT01474746 Sertraline SSRI 2–6 30 CGI-I,VAS Vineland-II, PSI-4, PLS-5, MSEL II/UC Davis OM:1↑CGI-I (46%),2 ↑VAS [262]
NCT01120626 Donepezil Cholinergic drug 12–29 45 ABC-C_T/CNT MRS, WM tests, CARS II/Stanford Pending
NCT01254945 Oxytocin Brain peptide 13–28 8 Eye gaze HR, RSA, HRV, cortisol Ib/Stanford OM:1↑Eye gaze, 2↓cortisol [77, 263]
NCT01329770 Vitamins C & E Antioxidants 6–18 30 DBC, WISC Tolerability II/Imabis Pending [264]
N/A Melatonin Hormone 2–15 15 Sleep times Actiwatch II/UC Davis OM:1↑sleep; [265]
N/A L-AcCarnitine Brain energy 6–13 63 ConnersGI-P Vineland-Survey, WISC-R II/TELETHON OM:1↓HI/I, 2↑Vineland [266]
N/A MPH/DAMP Stimulants 3–11 15 ConnersAbb ACTeRS, IQ measures II/Denver Child OM:1MPH:↓I, 2↓ACTeRS; [267]
  1. Modified from Table 1, Budimirovic and Phan [268] with permission
  2. Abbreviations: FDA Federal Drug Administration, GABA gamma-aminobutyric acid, ABC-C_I Aberrant Behavior Checklist-Community Edition (ABC-C), Irritability subscale, CGI-S Clinician Global Impression-Severity, CGI-I CGI improvement, VABS-II Vineland Adaptive Behavior Scale, Second Edition, SRS Social Responsiveness Scale, RBANS Repeatable Battery for the Assessment of Neurological Status, SB5 Stanford-Binet Version 5, ABC-C FX _SA ABC-CFX, Social Avoidance subscale, PSI Parenting Stress Index, CSHQ Children’s Sleep Habits Questionnaire, PPVT Peabody Picture Vocabulary Test, ADHD-RS Attention-Deficit Hyperactivity Disorder Rating Scale, ABC-C FX ABC-C, FXS-specific, ADAMS Anxiety Depression and Mood Scale, PPI prepulse inhibition, KiTAP Tests of Attentional Performance for Children, ERP evoked response potentials, ET eye tracking, SNAP-IV Swanson, Nolan and Pelhram Rating Scale, PARS Pediatric Anxiety Rating Scale, ABC-C_T ABC-C total score, ADAMS_T ADAMS total score, WISC-IV Wechsler Intelligence Scale for Children, 4th ed, CBI-M Caregiver Burden Inventory-Modified, MMP9 matrix metallopeptidase 9, VAS visual analog scale (VAS-C, clinician rated; VAS-mb, multiple behaviors; VAS-P, parent rated), mGluR5antagonist metabotropic glutamate receptor 1/5 antagonist, GABA/Glutamate GABA/glutamate normalizer, ABC-C_SW ABC-C, Lethargy/Social Withdrawal subscale, CSQ Caregiver Strain Questionnaire, ELS Expressive Language Sampling, Trofinetide Neu-2566-FXS-001 study, IGF-1 insulin-like growth factor, PLS-5 Preschool Language Scale-Version 5, MSEL Mullen Scales of Early Learning, CNT Contingency Naming Task, MRS magnetic resonance spectroscopy, WM working memory tests, CARS Childhood Autism Rating Scale, HR heart rate, RSA respiratory sinus arrhythmia, HRV heart rate variability, SSRI selective serotonin reuptake inhibitor, DBC Developmental Behavior Checklist, EVT-2 Expressive Vocabulary Test, 2nd ed, PK pharmacokinetics, ConnersGI-P Conners General Index-Parent Version, WISC-R WISC-Revised, MPH methylphenidate, DAMP dextroamphetamine, Conners Abb Conners Abbreviated Version, ACTeRS ADD-H Comprehensive Teacher’s Rating Scales, IQ intellectual quotient
  3. 1reflects a primary outcome measure (OM)
  4. 2reflects a secondary outcome measure (OM)
  5. Italized under Mechanism are clinical trials targeting excitatory-inhibitory imbalance in FXS