Alcobra just announced results from their trial of a proprietary formulation of metadoxine in fragile X subjects, and there is a glimmer of hope in their announcement (see here). While the drug did not show any beneficial effect on the primary outcome measure (essentially, an ADHD scale) it did result in some statistically significant improvement on 2 of 5 secondary measures. One of those showing improvement, the Vineland Adaptive Behavior Scale (VABS), is a well known and well validated outcome measure which has been used in other fragile X trials (though none of the other drugs resulted in improvement.) The other outcome measure showing improvement was the KiTAP, a computerized test of attention and distractibility. In both cases, the improvement was not only statistically significant, but also likely clinically meaningful; in other words, it was a relatively large effect.
The folks at Alcobra rightly note that this is the best showing to date for any drug in fragile X, and that both the KiTAP and VABS are appropriate and relevant outcome measures, and either could have been designated the primary outcome measure. The scale which was chosen as the primary endpoint, the ADHD RS-IV Inattentive subscale, was apparently chosen because the drug is thought to work mainly by enhancing attention, but the precise effect in fragile X could not have been anticipated.
It is possible that the VABS and KiTAP are just better or more useful scales for fragile X research, but it is also worth remembering that sometimes one or two secondary measures show apparent improvement which can’t be reproduced in subsequent trials. Alcobra has expressed interest in pursuing these findings, and they will presumably feature the VABS and KiTAP more prominently in the next round of metadoxine trials for fragile X. If they are able to reproduce these results, then this could be an important new treatment for fragile X.