Mechanisms of Metabolic and Hormone Action on Plaque Formation in Brain and Carotid Vessels in Patients With Prostate Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
This trial studies the mechanisms of metabolic and hormone action on plaque formation in brain and carotid vessels in patients with prostate adenocarcinoma. Studying the biomarkers in the laboratory may help doctors know the impact of androgen deprivation on metabolic, brain and cardiovascular endpoints.

Detailed Description
-----------------
OUTLINE: Patients undergo clinical evaluations over 12 months including physical exam and vital signs, waist to hip circumference, medical history and events, laboratory evaluations, imaging evaluations, cognitive function evaluations, gait assessment, and quality of life questionnaires.

Official Title
-----------------
Mechanisms of Metabolic and Hormone Action on Plaque Formation in Brain and Carotid Vessels in Men Undergoing Androgen Deprivation Therapy

Conditions
-----------------
Prostate Adenocarcinoma

Intervention / Treatment
-----------------
* Procedure: Evaluation
* Other: Quality-of-Life Assessment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent Histologically confirmed adenocarcinoma of the prostate Non-castrate disease with a serum testosterone level >= 50 ng/dL (1.73 nmol/L) at baseline No evidence of distant metastatic disease on baseline computed tomography-chest, abdomen and pelvis (CT-CAP) and bone scans Patients will be stratified by the presence or absence of pre-existing cardiovascular disease defined as at least one of the following: Prior myocardial infarction >= 30 days before enrollment Prior revascularization procedure >= 30 days before consent, including: Coronary artery stent placement or balloon angioplasty Coronary artery bypass graft surgery Stent placement or balloon angioplasty to a carotid, iliac, femoral, or popliteal artery Carotid endarterectomy surgery Vascular bypass surgery of the iliac, femoral, or popliteal artery Results from angiogram or CT angiogram of coronary, carotic, iliac, femoral, or popliteal arteries that documents at least one vascular stenosis >= 50% at any time point before enrollment Carotid ultrasound results that shows stenosis >= 50% at any time point before enrollment Ankle-brachial pressure index < 0.9 at any time point before enrollment Intent to initiate continuous androgen deprivation therapy (ADT) for at least 12 months Exclusion Criteria: No prior treatment with ADT at time of study entry. (Prior neoadjuvant/adjuvant ADT is allowed only if the last injection of a depot formulation wore off at least 12 months prior to enrollment) Previous or concurrent hormonal or systemic therapy for prostate cancer including: anti-androgens, estrogens, megestrol acetate, ketoconazole, abiraterone, enzalutamide, or chemotherapy. (Prior or planned neoadjuvant bicalutamide for prevention of tumor flare is allowed) Plans to start or continue treatment with an investigational product after enrollment Poorly controlled type 1 or type 2 diabetes mellitus, based on hemoglobin A1c, as judged by the investigator Prior or planned surgical castration Poorly controlled hypertension at time of study entry, as judged by the investigator Myocardial infarction or stroke < 30 days prior to enrollment Coronary, carotid, or peripheral artery revascularization < 30 days prior to enrollment Planned or scheduled cardiac surgery or percutaneous coronary intervention (PCI) procedure that is known at the time of enrollment Mental incapacity or language barrier precluding adequate understanding or cooperation Inability to tolerate magnetic resonance imaging (MRI) imaging, or both Lupron and Degarelix Any other clinically significant disorder which may affect the subject's health or the outcome of the trial as judged by the investigator Estimated glomerular filtration rate (eGFR) < 45 History of allergy to gadolinium contrast agent
Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Clinical Evaluations<br>Patients undergo clinical evaluations over 12 months including physical exam and vital signs, waist to hip circumference, medical history and events, laboratory evaluations, imaging evaluations, cognitive function evaluations, gait assessment, and quality of life questionnaires. | Procedure: Evaluation<br>* Undergo clinical evaluations<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in visual characterization of 18F-florbetapir (Amyvid) positron emission tomography (PET) scans results after Andorgen Deprivation Therapy | Change From Baseline visual characterization scan results at 12 months | 12 Months | 
| Change standardized uptake values of 18F-florbetapir (Amyvid) positron emission tomography (PET) scans results | Change from baseline standardized uptake values in select regions of interest at 12 months | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive test results: Story recall | Change in baseline Story Recall results at 12 months | 12 months | 
| Cognitive Test Results: Change in Montreal Cognitive Assessment (MOCA) | Change in baseline MOCA score results at 12 months | 12 Months | 
| Cognitive Test Results: Change in Clinical Dementia Rating Scale | Change in baseline Clinical Dementia Rating Scale score at 12 months | 12 Months | 
| Cognitive Test Results: Digit span | Change in baseline Digit span results at 12 months | 12 Months | 
| Cognitive Test Results: Letter number sequencing | Change in baseline Letter number sequencing results at 12 months | 12 Months | 
| Cognitive Test Results: Stroop Test Results | Change in baseline Stroop Test Results at 12 months | 12 Months | 
| Cognitive Test Results: Symbol Digit Modalities Test | Change in baseline Symbol Digit Modalities Test score at 12 months | 12 Months | 
| Cognitive Test Results: Visuo-Spatial Learning Test | Change in baseline Visuo-Spatial Learning Test results at 12 months | 12 Months | 
| Cognitive Test Results: Rey auditory verbal learning test (RVLT) | Change in baseline Rey auditory verbal learning test (RVLT) score at 12 months | 12 Months | 
| Inflammatory and immune markers: Change in CRP | Change in baseline CRP values at 12 months | 12 Months | 
| Inflammatory and immune markers: Change in IGFBP3 | Change in baseline IGFBP3 at 12 months | 12 Months | 
| Inflammatory and immune markers: Change in IGFBP1 | Change in baseline IGFBP1 at 12 months | 12 Months | 
| Inflammatory and immune markers: Change in IGF-1 | Change in baseline IGF-1 at 12 months | 12 Months | 
| Inflammatory and immune markers: Change in IL-6 | Change in baseline IL-6 at 12 months | 12 Months | 
| Metabolic Markers: Change in HgbA1C | Change in baseline HgbA1C at 12 months | 12 Months | 
| Metabolic Markers: Change in Estradiol | Change in baseline Estradiol at 12 months | 12 Months | 
| Metabolic Markers: Change in Follicle Stimulating Hormone (FSH) | Change in baseline Change in Follicle Stimulating Hormone (FSH) at 12 months | 12 Months | 
| Metabolic Markers: Change in Leptin | Change in baseline Leptin at 12 months | 12 Months | 
| Metabolic Markers: Change in Adiponectin | Change in baseline Adiponectin at 12 months | 12 Months | 
| Metabolic Markers: Change in homeostatic model assessment of insulin resistance (HOMA-IR) | Change in baseline HOMA-IR values at 12 months; Calculated based on fasting glucose and insulin test results. | 12 Months |