I tried the Reg Defragmentation once after I installed Reg Organizer ( Despite the fact that reg defrag does not improve anything I believe. As such I usually do not do it. ) and I kept Avast / MCShield and Glasswire active, and nothing bad happened. ( So no explosions and the likes. )When I tested it, I also have experienced a slow-down of the reg. scan.
However, during the registry cleaning and defragmentation it's needed to close all the apps, including AV.