Hi @tomschulze,
From the little I know I believe that changing any config at runtime on any nodejs, react, angular, etc project is not possible. Strapi is built on NodeJS therefore I think the answer is no.
If you change config and/or .env files on such projects you need to restart and rebuild, when rebuild is needed e.g. react, angular, starpi admin frontends etc.
I don’t know if there any workaround I can’t think of.
Hope I helped a bit.
Cheers 