Prostate Cancer
Conditions
Brief summary
Genistein is a natural supplement that comes from soy. The purpose of this study is to see if genistein has any effect on preventing or reducing heart disease and diabetes risk in men receiving Androgen Deprivation Therapy for prostate cancer. A combination of nutritional measures, blood markers and imaging tools will assess body composition, lipid levels and insulin resistance. Information from this pilot study will increase understanding of interventions which may prevent or reduce health risks during prostate cancer treatment. This project involves 24 men who will receive androgen deprivation therapy for prostate cancer.
Detailed description
This is a double-blind, randomized, placebo-controlled trial of daily oral genistein in 24 men initiating Androgen Deprivation Therapy (ADT) for prostate cancer (PCa). Genistein is a natural supplement that comes from soy. The purpose of this study is to see if genistein has any effect on preventing or reducing heart disease and diabetes risk in men receiving ADT for PCa. A combination of nutritional measures, blood markers and imaging tools will assess body composition, lipid levels and insulin resistance. Information from this study will increase understanding of interventions which may prevent or reduce health risks during prostate cancer treatment. All participants will receive standard counseling for diet and exercise by their oncology care team. Participants will be asked to withhold from any additional dietary supplements (with the exception of 1 standard daily multivitamin) during the study period. Participants will also be asked to complete a food diary for three days (on two weekdays and 1 weekend day). Subjects will be randomized and stratified by diabetes status to either 60 mg/day oral genistein (30 mg taken twice daily), or matching placebo. The goal for randomizing based on diabetes status is to ensure approximately the same number of subjects who have diabetes and do not have diabetes receive genistein and placebo. During follow-up, subjects will receive weekly reminders via phone call, text, or email to enhance compliance and monitor for potential adverse events. The 3-month study visit will be scheduled to coincide with the subject's standard of care follow-up visit. Three-month assessments will be the same as baseline assessments. Investigators seek to assess indexes of insulin dynamics (insulin sensitivity and secretion) determined from an oral glucose tolerance test before and 12 weeks after a daily genistein or placebo supplement. Measures of vascular function before and 12 weeks after a daily genistein or placebo supplement will also be assessed via ultrasound along with other metabolic measures via blood draw.
Interventions
DRUGGenistein
Genistein is a natural supplement that comes from soy. Genistein will be taken orally (30 mg twice daily) for 12 weeks.
DRUGPlacebo
A placebo pill will be taken orally for 12 weeks.
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Medical indication for androgen deprivation therapy (ADT) via luteinizing hormone-releasing hormone (LHRH) analog ± oral anti-androgen * Diagnosis of prostate cancer * ECOG performance status ≤ 2 * Life expectancy \> 6 months * Ability to provide informed consent
Exclusion criteria
* Transmural myocardial infarction, unstable angina, or congestive heart failure requiring hospitalization within the last 6 months * Acute coronary event within the past month * Use of intravenous antibiotics within the last 6 months * Chronic liver disease * Current use of cytotoxic or immunosuppressive drugs * Chronic glucocorticoid or acute glucocorticoid or other synthetic steroid intake within the last month * Chronic diarrhea or malabsorptive diseases (e.g., Crohn's disease) * Stage 5 chronic kidney disease or need for hemodialysis * Supplemental oxygen dependency * Brain metastasis * Severe cognitive dysfunction impairing ability to provide informed consent or consume study drug * Dysphagia or requirement for artificial feeding * Surgery or hospitalization within the last month * Chemotherapy or radiation therapy within the last 60 days * Insulin dependent diabetes * HIV/AIDS * History of organ transplant * ECOG performance status \> 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline | Baseline, Week 8 post-baseline | The Matsuda index is a measurement of insulin sensitivity from plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). Insulin sensitivity was calculated at baseline and after 8 weeks with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\]. Higher values are reflective of better insulin sensitivity. This test is not used to clinically diagnose disease, and there is no accepted, standard cutoff to define impaired insulin sensitivity or insulin resistance based on this index. |
| β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline | Baseline, Week 8 post-baseline | β-cell insulin secretion was determined from the OGTT. It is calculated as the ratio of the change in insulin values over the first 30 minutes of the OGTT and the change in glucose values over the first 30 minutes. Higher values are reflective of higher insulin secretion. This test is not used to clinically diagnose disease, and there is no accepted, standard cutoff to define impaired insulin secretion based on this index. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arterial Stiffness | Baseline, Week 8 | Arterial stiffness will be assessed by applanation tonometry. Results will be reported in m/s (meters/seconds). A higher value indicates a worse outcome. |
| Vascular Endothelial Function at Baseline and Week 8 Post-baseline | Baseline, Week 8 post-baseline | Vascular endothelial function was measured with flow-mediated dilation (FMD in %) via ultrasound. A lower FMD indicates a worse outcome. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled between October 2017 and March 2021. 10 participants consented to take part in the study and 2 withdrew at some point in the study. Results are presented on all data provided by all participants before withdrawal, where applicable.
Participants by arm
| Arm | Count |
|---|---|
| Genistein Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily).
Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily).
Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks. | 6 |
| Placebo Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks. | 4 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Genistein | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69.5 years | 67.5 years | 69.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| 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 | 1 Participants | 2 Participants | 3 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 2 Participants | 7 Participants |
| Region of Enrollment United States | 6 participants | 4 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 5 / 6 | 4 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 |
Outcome results
Primary
Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline
The Matsuda index is a measurement of insulin sensitivity from plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). Insulin sensitivity was calculated at baseline and after 8 weeks with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\]. Higher values are reflective of better insulin sensitivity. This test is not used to clinically diagnose disease, and there is no accepted, standard cutoff to define impaired insulin sensitivity or insulin resistance based on this index.
Time frame: Baseline, Week 8 post-baseline
Population: Number of patients included only subjects that were able to complete the outcome assessment in each visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Genistein | Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline | Baseline | 4.4 index |
| Genistein | Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline | 8 weeks post-baseline | 4.1 index |
| Placebo | Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline | 8 weeks post-baseline | 7.7 index |
| Placebo | Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline | Baseline | 6.1 index |
Primary
β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline
β-cell insulin secretion was determined from the OGTT. It is calculated as the ratio of the change in insulin values over the first 30 minutes of the OGTT and the change in glucose values over the first 30 minutes. Higher values are reflective of higher insulin secretion. This test is not used to clinically diagnose disease, and there is no accepted, standard cutoff to define impaired insulin secretion based on this index.
Time frame: Baseline, Week 8 post-baseline
Population: Number of patients included only subjects that were able to complete the outcome assessment in each visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Genistein | β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline | Week 8 post-baseline | 2.1 index |
| Genistein | β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline | Baseline | 1.1 index |
| Placebo | β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline | Baseline | 0.7 index |
| Placebo | β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline | Week 8 post-baseline | 1.4 index |
Secondary
Arterial Stiffness
Arterial stiffness will be assessed by applanation tonometry. Results will be reported in m/s (meters/seconds). A higher value indicates a worse outcome.
Time frame: Baseline, Week 8
Population: Number of patients included only subjects that were able to complete the outcome assessment in each visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Genistein | Arterial Stiffness | Baseline | 7.4 m/s |
| Genistein | Arterial Stiffness | Week 8 | 9.1 m/s |
| Placebo | Arterial Stiffness | Week 8 | 7.2 m/s |
| Placebo | Arterial Stiffness | Baseline | 7.2 m/s |
Secondary
Vascular Endothelial Function at Baseline and Week 8 Post-baseline
Vascular endothelial function was measured with flow-mediated dilation (FMD in %) via ultrasound. A lower FMD indicates a worse outcome.
Time frame: Baseline, Week 8 post-baseline
Population: Number of patients included only subjects that were able to complete the outcome assessment in each visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Genistein | Vascular Endothelial Function at Baseline and Week 8 Post-baseline | Baseline | 4.9 percentage of FMD |
| Genistein | Vascular Endothelial Function at Baseline and Week 8 Post-baseline | Week 8 post-baseline | 4.4 percentage of FMD |
| Placebo | Vascular Endothelial Function at Baseline and Week 8 Post-baseline | Baseline | 4.7 percentage of FMD |
| Placebo | Vascular Endothelial Function at Baseline and Week 8 Post-baseline | Week 8 post-baseline | 2.7 percentage of FMD |