Propranolol Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

Evaluating the Effect of ADRB2 Blockers on PKA/BAD/CREB Signaling in Patients Undergoing Prostatectomy

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Other: Survey Administration; Drug: Propranolol Hydrochloride

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 Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center of Wake Forest University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (propranolol hydrochloride); Patients receive propranolol hydrochloride PO 2 hours prior to standard of care prostatectomy.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Other: Survey Administration; Ancillary studies; Drug: Propranolol Hydrochloride; Given PO; Other Names: Inderal; Innopran XL
Active Comparator: Group II (no treatment); Patients receive no treatment prior to standard of care prostatectomy.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Other: Survey Administration; Ancillary studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CREB phosphorylation	Will be determined by western blot in prostate tissue from men.	2 hours after taking or not taking propranolol prior to prostatectomy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BAD phosphorylation	Will be assessed by western blot in prostate tissue from men. 2-sample t-tests will be calculated to compare the groups who were randomized to receive propranolol (yes/no). Descriptive statistics will be calculated for each measure within each group. These statistics include n, mean, standard deviations and 95% confidence intervals.	2 hours after taking or not taking propranolol prior to prostatectomy
Distress score	Will be measured by The Distress Thermometer from men. 2-sample t-tests will be calculated to compare the groups who were randomized to receive propranolol (yes/no). Descriptive statistics will be calculated for each measure within each group. These statistics include n, mean, standard deviations and 95% confidence intervals.	On the day of surgery before taking propranolol, prior to prostatectomy
Levels of transcripts that reflect ADRB2/PKA activation	Difference in levels of transcripts that reflect ADRB2/PKA activation will be measured by real-time polymerase chain reaction in prostate tissue from men. 2-sample t-tests will be calculated to compare the groups who were randomized to receive propranolol (yes/no). Descriptive statistics will be calculated for each measure within each group. These statistics include n, mean, standard deviations and 95% confidence intervals.	2 hours after taking or not taking propranolol prior to prostatectomy
Plasma catecholamine levels (including epinephrine)	Will be measured by enzyme-linked immunosorbent assay from men. 2-sample t-tests will be calculated to compare the groups who were randomized to receive propranolol (yes/no). Descriptive statistics will be calculated for each measure within each group. These statistics include n, mean, standard deviations and 95% confidence intervals.	2 hours after taking or not taking propranolol prior to prostatectomy
Plasma propranolol levels	Will be measured by fluorometric detection from men. 2-sample t-tests will be calculated to compare the groups who were randomized to receive propranolol (yes/no). Descriptive statistics will be calculated for each measure within each group. These statistics include n, mean, standard deviations and 95% confidence intervals.	2 hours after taking or not taking propranolol prior to prostatectomy
Self-perceived stress	Will be measured by The Perceived Stress Questionnaire from men. 2-sample t-tests will be calculated to compare the groups who were randomized to receive propranolol (yes/no). Descriptive statistics will be calculated for each measure within each group. These statistics include n, mean, standard deviations and 95% confidence intervals.	On the day of surgery before taking propranolol, prior to prostatectomy

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ashok Hemal, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Actual): June 15, 2021
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: May 9, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 15, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: IRB00043227; P30CA012197 (U.S. NIH Grant/Contract); NCI-2017-00788 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CCCWFU 85716 (Other Identifier: Comprehensive Cancer Center of Wake Forest University)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No