Autonomic Phenotype Before and After Akt Inhibition

Some Akt inhibitors have produced functional cardiovascular effects such as marked hypotension that may limit their clinical benefit. There are no current data on whether this autonomic failure presents in humans at clinically used doses. We will test the hypothesis that Akt inhibition causes an acute decrease in sympathetic tone and lowers blood pressure.

Patients will have a diagnosis of Melanoma and be participating in a clinical trial with an arm using oral Akt therapy. Patients will be recruited from the Vanderbilt Ingram Cancer Center.

• Behavioral: Autonomic Function Tests
  Patients will undergo Autonomic Function testing (AFT) before and 8 hours after Akt Inhibition therapy. AFT includes: Supine & standing heart rate & blood pressure, 10 minute head up tilt, cardiac output, sinus arrhythmia, hyperventilation, sustained handgrip, valsalva manuever, and cold pressor test.
• Other: supine and standing catecholamines
  patients will have blood drawn from supine and standing catecholamines.

Inclusion Criteria:

• Diagnosed with melanoma with a BRAF mutation and relapse following therapy with a BRAF inhibitor
• Enrolled in a clinical trial through the Vanderbilt Ingram Cancer Center (VICC) including an arm with an oral Akt inhibitor
• Able and willing to provide informed consent

Exclusion Criteria:

• Factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule
• Unable to give informed consent