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There's a user permission problem with lets encrypt and mpm-itk.

Can you please add/modify following section in /etc/apache2/site-enabled/000-ispconfig.conf

[..]
<Directory /usr/local/ispconfig/interface/acme/.well-known/acme-challenge>
                                Require all granted
                                <IfModule mpm_itk_module>
                                          AssignUserId www-data www-data
                                </IfModule>
 </Directory>
[..]