First off, I'm no expert. With that said...it sounds like you have tried:weekly water changes, substrate changes, regular testing all to no real change. It sounds like the fish in your tank are producing lots of waste, or possibly not all of the food is getting eaten(does not sound like this is the case).
If this were my tank I would definitley increase mechanical filtration, to remove waste more often. I would also use fine filtration in canisters and change weekly. And also do regular water changes 5-7 days. If these are not viable options, maybe cut back on feeding or remove some fish. BTW plecos are mass waste producers.
I have a largely over stocked 220g, that gets a 40%+ water change on average every 4 days, and I change out mechanical filtration every two days. With this process my nitrates stay below 40ppm, but if I fail to keep up the routine, the nitrates sky rocket.
Good luck and keep us updated on your progress.