Prostate Carcinoma
Conditions
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPropranolol Hydrochloride
Given PO
OTHERQuestionnaire Administration
Ancillary studies
OTHERSurvey Administration
Ancillary studies
Sponsors
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
19 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Level of CREB Phosphorylation | 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
| Measure | Time frame | Description |
|---|---|---|
| BAD Phosphorylation | 2 hours after taking or not taking propranolol prior to prostatectomy | Will be assessed by western blot in prostate tissue from men. BAD is a protein that plays a critical role in cell survival. Phosphorylation alters the structural conformation of a protein, causing it to become activated, deactivated, or otherwise modifying its function. This analysis shows how much phosphorylation of BAD protein is happening in cells. |
| Distress Score - National Comprehensive Cancer Network Distress Thermometer Questionnaire | On the day of surgery before taking propranolol, prior to prostatectomy | Will be measured by The Distress Thermometer from men. The NCCN Distress Thermometer (DT) is a one-item, 11-point Likert scale represented on a visual graphic of a thermometer that ranges from 0 (no distress) to 10 (extreme distress), with which patients indicate their level of distress over the course of the week prior to assessment. Scoring scale ranges from 0 (no distress) to 10 (extreme distress) with higher scores indicating more distress. |
| Levels of Transcripts That Reflect ADRB2/PKA Activation | 2 hours after taking or not taking propranolol prior to prostatectomy | Difference in levels of transcripts that reflect ADRB2/PKA activation will be measured by real-time polymerase chain reaction in prostate tissue from men. |
| Plasma Catecholamine Levels (Including Epinephrine) | 2 hours after taking or not taking propranolol prior to prostatectomy | 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. |
| Plasma Propranolol Levels | 2 hours after taking or not taking propranolol prior to prostatectomy | 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. |
| Self-perceived Stress | On the day of surgery before taking propranolol, prior to prostatectomy | Will be measured by The Perceived Stress Questionnaire from men. The perceived stress questionnaire is a set of 4 questions asking participants about their feelings/problems with stress over the last two weeks. Scoring scale ranges from 0 to 16 with higher scores indicating a higher level of stress. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAshok Hemal
Wake Forest University Health Sciences
Participant flow
Recruitment details
January 15, 2019 to June 8, 2021
Participants by arm
| Arm | Count |
|---|---|
| Group I (Propranolol Hydrochloride) Patients receive propranolol hydrochloride PO 2 hours prior to standard of care prostatectomy.
Laboratory Biomarker Analysis: Correlative studies
Propranolol Hydrochloride: Given PO
Questionnaire Administration: Ancillary studies
Survey Administration: Ancillary studies | 23 |
| Group II (no Treatment) Patients receive no treatment prior to standard of care prostatectomy.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Survey Administration: Ancillary studies | 23 |
| Total | 46 |
Baseline characteristics
| Characteristic | Group II (no Treatment) | Total | Group I (Propranolol Hydrochloride) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 29 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 17 Participants | 8 Participants |
| Age, Continuous | 64.61 years STANDARD_DEVIATION 64.61 | 66.48 years STANDARD_DEVIATION 6.71 | 68.35 years STANDARD_DEVIATION 6.21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 18 Participants | 33 Participants | 15 Participants |
| Region of Enrollment United States | 23 participants | 46 participants | 23 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 23 Participants | 46 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Mean Level of CREB Phosphorylation
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.
Time frame: 2 hours after taking or not taking propranolol prior to prostatectomy
Population: levels of total CREB signal were below detection limit in missing participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Propranolol Hydrochloride) | Mean Level of CREB Phosphorylation | 1.34 West blot band intensity,arbitrary units | Standard Deviation 0.33 |
| Group II (no Treatment) | Mean Level of CREB Phosphorylation | 1.43 West blot band intensity,arbitrary units | Standard Deviation 0.46 |
Secondary
BAD Phosphorylation
Will be assessed by western blot in prostate tissue from men. BAD is a protein that plays a critical role in cell survival. Phosphorylation alters the structural conformation of a protein, causing it to become activated, deactivated, or otherwise modifying its function. This analysis shows how much phosphorylation of BAD protein is happening in cells.
Time frame: 2 hours after taking or not taking propranolol prior to prostatectomy
Population: BAD phosphorylation not detected
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Propranolol Hydrochloride) | BAD Phosphorylation | 0 kDa | Standard Deviation 0 |
| Group II (no Treatment) | BAD Phosphorylation | 0 kDa | Standard Deviation 0 |
Secondary
Distress Score - National Comprehensive Cancer Network Distress Thermometer Questionnaire
Will be measured by The Distress Thermometer from men. The NCCN Distress Thermometer (DT) is a one-item, 11-point Likert scale represented on a visual graphic of a thermometer that ranges from 0 (no distress) to 10 (extreme distress), with which patients indicate their level of distress over the course of the week prior to assessment. Scoring scale ranges from 0 (no distress) to 10 (extreme distress) with higher scores indicating more distress.
Time frame: On the day of surgery before taking propranolol, prior to prostatectomy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Propranolol Hydrochloride) | Distress Score - National Comprehensive Cancer Network Distress Thermometer Questionnaire | 3.6 score on a scale | Standard Deviation 2.3 |
| Group II (no Treatment) | Distress Score - National Comprehensive Cancer Network Distress Thermometer Questionnaire | 2.7 score on a scale | Standard Deviation 2.6 |
Secondary
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.
Time frame: 2 hours after taking or not taking propranolol prior to prostatectomy
Population: insufficient material for RNA extraction
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group I (Propranolol Hydrochloride) | Levels of Transcripts That Reflect ADRB2/PKA Activation | NA relative gene expression |
| Group II (no Treatment) | Levels of Transcripts That Reflect ADRB2/PKA Activation | NA relative gene expression |
Secondary
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.
Time frame: 2 hours after taking or not taking propranolol prior to prostatectomy
Population: one blood sample was missing during Epi measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Propranolol Hydrochloride) | Plasma Catecholamine Levels (Including Epinephrine) | 0.36 nano mole (nm) per liter (L) | Standard Deviation 0.22 |
| Group II (no Treatment) | Plasma Catecholamine Levels (Including Epinephrine) | 0.34 nano mole (nm) per liter (L) | Standard Deviation 0.22 |
Secondary
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.
Time frame: 2 hours after taking or not taking propranolol prior to prostatectomy
Population: Number of samples collected for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Propranolol Hydrochloride) | Plasma Propranolol Levels | 10.89 nanograms per milliliter (ng/ml) | Standard Deviation 4.58 |
| Group II (no Treatment) | Plasma Propranolol Levels | 0.00 nanograms per milliliter (ng/ml) | Standard Deviation 0 |
Secondary
Self-perceived Stress
Will be measured by The Perceived Stress Questionnaire from men. The perceived stress questionnaire is a set of 4 questions asking participants about their feelings/problems with stress over the last two weeks. Scoring scale ranges from 0 to 16 with higher scores indicating a higher level of stress.
Time frame: On the day of surgery before taking propranolol, prior to prostatectomy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Propranolol Hydrochloride) | Self-perceived Stress | 7.4 score on a scale | Standard Deviation 2.3 |
| Group II (no Treatment) | Self-perceived Stress | 8.2 score on a scale | Standard Deviation 1.4 |