For what it's worth, I can in theory create a ST_GEOMETRY function-based spatial index:
create index atn_startpoint_shape on infrastr.active_transportation (sde.st_geomfromwkb(sde.st_asbinary(sde.st_startpoint(sde.st_geometryn(shape,1))),300125)) indextype is SDE.ST_SPATIAL_INDEX parameters ('ST_GRIDS=320 ST_SRID=300125');
Index ATN_STARTPOINT_SHAPE created.
But there doesn't seem to be a way to utilize that index in the map in ArcGIS Pro. For example, I wouldn't insert a row into USER_SDO_GEOM_METADATA for ST_GEOMETRY spatial index, since that's designed for SDO_GEOMETRY columns only.
When I try to test a view that would use the index in ArcMap...
create or replace view atn_startpoint_vw as ( select objectid, sde.st_geomfromwkb(sde.st_asbinary(sde.st_startpoint(sde.st_geometryn(shape,1))),300125) shape from infrastr.active_transportation where sde.st_geomfromwkb(sde.st_asbinary(sde.st_startpoint(sde.st_geometryn(shape,1))),300125) is not null )