There are numerous reports online of users having intermittent problems connecting to RemoteApp applications using remote gateway.  The information here relates specifically to remote gateway on server 2012 R2 )but similar issues may well exist on Server 2008 R2 gateway).

The main issue is that if you launch a Remote App from the browser

then depending on the version of the RDP client you have installed it may not close cleanly when you exit.  There is no visible sign of this unless you look in your Task manager and see that the mstsc.exe process is still running, but it will prevent you from starting the application again.

There are a number of workarounds to this:

1) Simply end the process in the Task manager – this will allow you to run the RemoteApp again.  Clearly this is not a great solution ultimately but is an easy short term fix.

2) Running the RDP connection directly (rather than as a RemoteApp) means it will run again – though it may still not exit cleanly and you will end up with multiple mstsc.exe processes in your task manager.  You can also on occasion be left with a black window on exiting which takes a few seconds before you can close it.

3) This problem seems to occur when the Remote desktop client supports a protocol less than 8.1.  Upgrading this has so far in our tests resolved the issue so ultimately is clearly the best approach/

Upgrade to a version that supports Protocol 8.1 or better – updates available here: http://support.microsoft.com/kb/2830477/en-us

If using 7.1 protocol - make sure that the RDP connection file does NOT have "bypass gateway for local connections ticked" as this attempts to connect (multiple times) on port 3389 and waits for a timeout adding a couple of 30 second delays into the connection.