Evaluating the Effect of ADRB2 Blockers on PKA/BAD/CREB Signaling in Patients Undergoing Prostatectomy
Overview
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Mean Level of CREB Phosphorylation
Overview
Brief Summary
This randomized pilot clinical trial studies how well propranolol hydrochloride works in treating patients with prostate cancer who are undergoing surgery. When stressed, the body makes a molecule that may prevent tumor cells from dying, and propranolol hydrochloride may affect the signals in cells that cause tumor cells survival and death.
Detailed Description
PRIMARY OBJECTIVES:
I. To compare activation of ADRB2/PKA/BAD signaling pathway in the prostate glands of men two hours after taking or not taking propranolol hydrochloride (propranolol) prior to prostatectomy, as indicated by phosphorylated CREB.
SECONDARY OBJECTIVES:
I. To compare activation of ADRB2/PKA/BAD signaling pathway in the prostate glands of men two hours after taking or not taking propranolol prior to prostatectomy as indicated by phosphorylated BAD.
II. To determine the difference in candidate transcript levels associated with ADRB2/PKA activation between individuals two hours after taking propranolol or not taking propranolol prior to prostatectomy.
III. To determine plasma propranolol levels in individuals taking propranolol two hours after administration prior to prostatectomy.
IV. To determine if plasma catecholamine levels in men with prostate cancer can be used as a biomarker to identify patients who show activation of ADRB2 signaling pathway in prostate tumors.
V. To determine perceived stress level differences in men with prostate cancer prior to surgery to examine possible association between perceived stress level and catecholamine levels in blood and activation of ADRB2 pathway in tumors.
VI. To determine perceived distress level differences in men with prostate cancer prior to surgery to examine possible association between distress level and catecholamine levels in blood and activation of ADRB2 pathway tumors.
OUTLINE: Patients are randomized into 1 of 2 groups.
GROUP I: Patients receive propranolol hydrochloride orally (PO) 2 hours prior to standard of care prostatectomy.
GROUP II: Patients receive no treatment prior to standard of care prostatectomy.
After completion of study treatment, patients are followed up for 30 days.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 19 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of prostate cancer undergoing prostatectomy
- •Individuals able to understand and willing to sign an Institutional Review Board (IRB)-approved informed consent document
Exclusion Criteria
- •Men taking propranolol on a daily for any reason are excluded
- •Men with baseline systolic blood pressure (SBP) \< 110 or heart rate (HR) \< 60
- •Men unable to swallow pills
- •History of current or past medical or psychiatric illness that would make participation difficult or not feasible at the discretion of the principal investigator or co-investigators
Arms & Interventions
Group I (propranolol hydrochloride)
Patients receive propranolol hydrochloride PO 2 hours prior to standard of care prostatectomy.
Intervention: Laboratory Biomarker Analysis (Other)
Group I (propranolol hydrochloride)
Patients receive propranolol hydrochloride PO 2 hours prior to standard of care prostatectomy.
Intervention: Propranolol Hydrochloride (Drug)
Group I (propranolol hydrochloride)
Patients receive propranolol hydrochloride PO 2 hours prior to standard of care prostatectomy.
Intervention: Questionnaire Administration (Other)
Group I (propranolol hydrochloride)
Patients receive propranolol hydrochloride PO 2 hours prior to standard of care prostatectomy.
Intervention: Survey Administration (Other)
Group II (no treatment)
Patients receive no treatment prior to standard of care prostatectomy.
Intervention: Laboratory Biomarker Analysis (Other)
Group II (no treatment)
Patients receive no treatment prior to standard of care prostatectomy.
Intervention: Questionnaire Administration (Other)
Group II (no treatment)
Patients receive no treatment prior to standard of care prostatectomy.
Intervention: Survey Administration (Other)
Outcomes
Primary Outcomes
Mean Level of CREB Phosphorylation
Time Frame: 2 hours after taking or not taking propranolol prior to prostatectomy
Determined using western blot in prostate tissue from men. CREB is a type of protein that binds to DNA in very specific places. CREB is related to long-term memory formation in the brain and is important in the formation of spatial memory. Phosphorylation alters the structural conformation of a protein, causing it to become activated, deactivated, or otherwise modifying its function. The level of CREB phosphorylation is an indicator of BAD activity.
Secondary Outcomes
- BAD Phosphorylation(2 hours after taking or not taking propranolol prior to prostatectomy)
- Distress Score - National Comprehensive Cancer Network Distress Thermometer Questionnaire(On the day of surgery before taking propranolol, prior to prostatectomy)
- Levels of Transcripts That Reflect ADRB2/PKA Activation(2 hours after taking or not taking propranolol prior to prostatectomy)
- Plasma Catecholamine Levels (Including Epinephrine)(2 hours after taking or not taking propranolol prior to prostatectomy)
- Plasma Propranolol Levels(2 hours after taking or not taking propranolol prior to prostatectomy)
- Self-perceived Stress(On the day of surgery before taking propranolol, prior to prostatectomy)