MSSQL Timeout Expired in ASP.NET C# WebForms application

I have the following issue on my database which is used by a c# ASP.NET application:

Timeout expired. The timeout period elapsed prior to completion of the operation or the server is not responding.

I've tried sp_who and sp_who2 to check the cmd's visible there, which shows there is an average connectioncount of 10 users with AWAITING COMMAND and one CHECKPOINT.

The only way I can fix this database for several days is to take the application offline and take the database offline. Afterwards I can put the database back online and it will function without problems for a few days.

This is not a solid solution because the problem keeps coming back. But I'm out of thoughts what I can try.

What are the next steps for me to find the cause of this issue?