Sorry hux, this is not the most popular kind of problem, generally giving one a tough time trying to help troubleshooting it from a distance and way over my head.
I experienced something similar only once and it had to do with a certain combination of plugins plus a SynthEdit based plugin. My remedy was removing the SE plugin.
- Does the project only have the plugins you mentioned or are there also some other plugins in there? Does it happen with other projects? Can you upload the .RPP project file?
- Another approach to the plugin question: Start the problem project in "recovery mode" (open your project from the 'File->Open' dialog and check the "Recovery mode" checkbox). Then play the loop and bring the plugins back online one by one and give each one enough time to make Reaper go bonkers.
- Did you try playing with the 'Track performance options' like "Prevent anticipative FX" e.g. for the tracks with the ampsims yet?
- If you monitor the memory usage while this happens, does it rise continually (memory leak)? Are your CPU cores showing a roughly equal load?
That's all I can think of atm.