The dosage of carvedilol will be gradually increased from the initial recommended starting dose of 3.125 mg twice/daily, the target dose will be 25mg twice daily (50 mg/day) and participants will take 50 mg/day carvedilol for 6 months.Subjects that cannot tolerate the 50 mg daily dose, will be offered to continue at the 25 mg daily dose.

REM Sleep Behavior Disorder

Pre-motor Parkinson Disease

Symptomatic Parkinson Disease

At the end of Baseline visit, carvedilol 3.125 twice daily will be initiated and maintained for 1 week, increased to 6.25twice daily (dispensed at week 1visit), to 12.5mg twice daily (dispensed at week 2) and a max dose of 25mg twice daily (dispensed at week 4 visit), as tolerated. A subject that cannot tolerate at least a 25 mg daily dose will be excluded from the study. Subjects that cannot tolerate the 50 mg daily dose, will be offered to continue at the 25 mg daily dose. The project will include a washout period at study end.

Carvedilol

Cedars Sinai Medical Center

Adrenergic Blockers for Cardiac Changes in Early Parkinson's Disease

The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease

123I-MIBG reuptake will be measured by early and late Heart to Mediastinal ratio (H/M) and Washout ratio (WR) which will be calculated using the following formula: [(early heart counts/pixel - early mediastinum counts/pixel) - (late heart counts/pixel decay-corrected - late mediastinum counts/pixel decay-corrected)]/(early heart counts/pixel - early mediastinum counts/pixel). Care will be taken to exclude lung or liver from the myocardial and large vessels and lung from the mediastinum region of interest. MIBG abnormality cutoffs will be set for values of late H/M <2.2 and WR >30%.

Safety will be monitored collecting the type and frequency of adverse events, including clinical symptoms, changes in vital signs, clinical laboratory measures and EKG abnormalities.

Twenty-four-hour Holter monitoring of all patients will be conducted at two points during the study: 1) After MIBG and prior to the administration of the study drug and 2) within one week of the end of the six-month treatment trial. Two-channel Holter recordings will obtained and analyzed on a commercially available scanner in the cardiac laboratory at Cedars Sinai Medical Center, according to published guidelines.

The Movement disorder society-unified Parkinson's disease rating scale (MDS-UPDRS) Part III will be administered at baseline and 26 weeks after study medication titration. Each item of the MDS-UPDRS has a possible rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe.Clinical scales will be performed OFF medication in those subjects that might be receiving dopaminergic drugs

RBD questionnaire (RBDSQ) changes from Screening at 26 weeks after study drug titration

University of Pennsylvania Smell Identification Test (UPSIT) changes from screening at 26 weeks after study medication titration

Functional constipation will be assessed at screening and at 26 weeks after study medication titration using a questionnaire based on modified ROME III diagnostic criteria, which focuses on symptoms including straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction or blockage, manual maneuvers to facilitate evacuation, and two or fewer bowel movements per week. This questionnaire is based on a six item self-report measures with a three point summated rating scale. The total score has a range of 0 to 12, with scores > 4 identifying functional constipation.

Color vision changes will be assessed using HRR Pseudochromatic Plates from screening at 26 weeks after study medication titration

DaT/SPECT uptake at baseline will be quantified at baseline and 26 weeks after study medication titration

The NMSS measures non-motor symptoms over the previous month. Each symptom is scored with respect to: Severity: 0 = None, 1 = Mild; 2 = Moderate; 3 = Severe and Frequency: 1 = Rarely (<1/wk); 2 = Often (1/wk); 3 = Frequent (several times per week); 4 = Very Frequent (daily or all the time).

The SCOPA-AUT scale consists of 25 items assessing autonomic symptoms in the following regions: gastrointestinal (7), urinary (6), cardiovascular (3), thermoregulatory (4), pupillomotor (1), and sexual (2 items for men and 2 items for women) dysfunction.

Peripheral IR will be defined by testing for fasting plasma insulin (FPI), fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) from baseline at 26 weeks after study medication titration. HOMA index will be calculated by the formula: HOMA-IR = (FPI x FPG)/405. [A cutoff HOMA index of 2.0, equivalent to <50% sensitivity, will be used to define IR. Subjects were considered to have IR if they either had a HOMA≥2.0 and/or HbA1c≥5.7.

Measures of insulin sensitivity in neuronal-origin enriched plasma EVs (central IR) will be used to test the association of changes in such sensitivity to changes in MIBG uptake and clinical scores from baseline to 26 weeks after carvedilol titration. For that purpose, plasma samples will be collected and stored and -80oC to allow for isolation of neuronal origin EVs at the completion of the study.

Michele Tagliati, MD

Professor of Neurology, Director of Movement Disorders

Treatment: carvedilol titration; Experimental treatment with carvedilol will be offered at stabilized medical treatment. The dosage of carvedilol will be gradually increased from the initial recommended starting dose of 3.125mg twice daily and will be doubled every week according to patient tolerability, as measured by subjective complaints, arterial blood pressure and heart rate. The target dose will be 25mg twice daily (50 mg/day). Subjects that cannot tolerate the 50 mg daily dose, will be offered to continue at the 25 mg daily dose.

Healthy volunteers. Liver donor groups; Course of the research: Blood samples from all groups shall be taken for S100β and NSE in preoperative period, in the operating room and after 1 and 6 months in postoperative period. Mortality and morbidity of the patients shall be recorded. Neurological damage and its effect on prognosis shall be examined within the patients who were transplanted liver with S100β and NSE. Demographic data of the patients, accompanying diseases, American Society of Anesthesia classification, etiology, Model For End-Stage Liver Disease score, Child classification, sodium, potassium, total bilirubin, alanine aminotransferase, aspartate aminotransferase, Alkaline phosphatase, International Normalized Ratio, creatinine and urea shall be recorded. Intraoperative medicine administration and fluid balance, duration of operation, graft hot ischemia and graft cold ischemia durations, initial pulmonary artery pressure, blood component transplantations shall be recorded.

Liver transplant groups;Course of the research Blood samples from all groups shall be taken for S100β and NSE in preoperative period, in the operating room and after 1 and 6 months in postoperative period. Mortality and morbidity of the patients shall be recorded. Neurological damage and its effect on prognosis shall be examined within the patients who were transplanted liver with S100β and NSE. Demographic data of the patients, accompanying diseases, American Society of Anesthesia classification, etiology, Model For End-Stage Liver Disease score, Child classification, sodium, potassium, total bilirubin, alanine aminotransferase, aspartate aminotransferase, Alkaline phosphatase, International Normalized Ratio, creatinine and urea shall be recorded. Intraoperative medicine administration and fluid balance, duration of operation, graft hot ischemia and graft cold ischemia durations, initial pulmonary artery pressure, blood component transplantations shall be recorded.

analyzing S100β and neuron specific enolase serum concentrations

Liver Transplantation

S100β is 10.4 kDa protein. Synthesized with end feet processes of astrocytes in the brain S100β belongs to low molecular weight EF-hand type acidic calcium binding protein superfamily. This protein is metabolized in the kidneys and removed with urine. It is shown that S100β does not show differences due to ethnical groups or genders and is not affected by circadian rhythm. Although S100β is also found in other tissues, it is in higher concentrations in the brain so it can be used as an early indicator for brain damage.NSE is an SSS protein which exists in neurons and neuroendocrine tissues. NSE plays a role in glycolytic route in neurons as intracytoplasmic enzyme increasing serum level in case of neuron damage. Whilst S100β is the marker of astroglia dysfunction, NSE is the marker of neuronal dysfunction.

S100β and Neuron specific enolase (NSE)

Akdeniz University Medical Faculty Department of Anesthesiology and Reanimation

S100β and Neuron Specific Enolase Levels in Liver Transplantation

Evaluation of Preoperative and Postoperative S100β and Neuron Specific Enolase Levels in Patients Undergoing Liver Transplantation

Blood sample is taken in preoperative period before induction of anesthesia in the operating room to analyze S100β serum concentrations and neurologic damage of liver transplantation patients besides evaluating its effect on prognosis.

Blood sample is taken first month in postoperative period to analyze S100β serum concentrations and neurologic damage of liver transplantation patients besides evaluating its effect on prognosis

Blood sample is taken sixth month in postoperative period to analyze S100β serum concentrations and neurologic damage of liver transplantation patients besides evaluating its effect on prognosis.

Blood sample is taken in preoperative period before induction of anesthesia in the operating room to analyze Neuron specific Enolase serum concentrations and neurologic damage of liver transplantation patients besides evaluating its effect on prognosis.

Blood sample is taken first month in postoperative period to analyze Neuron specific Enolase serum concentrations and neurologic damage of liver transplantation patients besides evaluating its effect on prognosis.

Blood sample is taken sixth month in postoperative period to analyze Neuron specific Enolase serum concentrations and neurologic damage of liver transplantation patients besides evaluating its effect on prognosis.

The aim of the study is to evaluate neurological damage and analyze its effect on prognosis by considering S100β and NSE levels in liver transplantation.

Bora Dinc

Assistant Professor Department of Anesthesiology and Reanimation

Osteoarthritis

AquaCal and AquaPT are produced by Marigot Ltd according to EU and FDA requirements.
The daily dose of 4 capsules of AquaCal provide 800mg calcium, (the EU RDA for calcium) and 74 mgs Magnesium (EU RDA 375mg).

AquaCal

AquaCal and AquaPT are produced by Marigot Ltd according to EU and FDA requirements.
The daily dose of 4 capsules of AquaPT provides 720mg calcium, 200mgs green tea (polyphenols) and 50 mgs pine bark extract.

AquaPT

Cork University Hospital

A Study to Determine if Aquamin Modulates Inflammatory Biomarkers in the Blood of Osteoarthritis and Healthy Subjects

Randomised, Placebo Controlled Study to Determine if Aquamin (as AquaCal and AquaPT) Modulates Inflammatory Biomarkers in the Blood of Osteoarthritis and Healthy Subjects

Plasma cytokine concentrations (including TNFα, IL-β, NFκB, COX2 & IL-6)

Western Ontario and McMaster Universities Arthritis Index

Haemaglobin, white cell count, platelet count, haematocrit, differential white count

Including Sodium, Potassium, Chloride, Urea, Creatinine, Protein, Albumin

Andrea Doolan

Human Studies Manager

Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration). Patients also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration) alone.

Androgen-Deprivation Therapy and Docetaxel

Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration).

Androgen-Deprivation Therapy Alone

Total

Sex: Female, Male

Overall survival is defined as the time from randomization to death or date last known alive. Survival data reflects the database as of December 23, 2013.

Overall Survival

Time to clinical progression is defined as the time from randomization to clinical progression. Clinical progression is defined as increasing symptomatic bone metastases, progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria or clinical deterioration due to cancer per investigator's opinion. Patients without documented clinical progression were censored at the date of last disease assessment. Secondary endpoint data reflect the database as of December 23, 2014.

Time to Clinical Progression

Time to castration resistant prostate cancer is defined as the time from randomization to PSA progression or clinical progression, whichever occurred first. Patients without documented progression were censored at the date of last disease assessment. Secondary endpoint data reflect the database as of December 23, 2014.

Time to Castration Resistant Prostate Cancer (Hormone Refractory Disease)

PSA CR is defined as a PSA level less than 0.2 ng/ml measured for 2 consecutive measurements at least 4 weeks apart. Patients who met the criterion of PSA CR and had PSA level less than 0.2 ng/ml before and after the 6-month time point are considered as having a PSA CR at 6 months.

Proportion of Patients With PSA Complete Response (CR) at 6 Months

PSA CR is defined as a PSA level less than 0.2 ng/ml measured for 2 consecutive measurements at least 4 weeks apart. Patients who met the criterion of PSA CR and had PSA level less than 0.2 ng/ml before and after the 12-month time point are considered as having a PSA CR at 12 months.

Proportion of Patients With PSA Complete Response (CR) at 12 Months

The primary QOL change was evaluated by the Functional Assessment of Cancer Therapy - Prostate (FACT-P) instrument. FACT-P is a self-report measure of both general and disease-specific QOL. Higher scores represent better QOL. The FACT-P (version 4) contains 39 likert items distributed over 5 subscales: physical (7 items), social/family (7 items), emotional (6 items), and functional (7 items) well-being, and the additional concerns related to prostate cancer scale (12 items). The FACT-P total score is calculated by summing all these 5 subscales and ranges from 0 to 156.

QOL Change From Baseline to 3 Months

Overall Study

Study Statistician

Arm A

Arm B

Metastatic Hormone-sensitive Prostate Cancer

LHRH analogs are administered with a variety of techniques such as subcutaneously, intramuscularly, or insertion, while antiandrogens (flutamide and bicalutamide) were given orally.

androgen-deprivation therapy

docetaxel

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Providence Cancer Center

Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital

Mayo Clinic Hospital

Mayo Clinic Scottsdale

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Alta Bates Summit Comprehensive Cancer Center

Peninsula Medical Center

California Cancer Care, Incorporated - Greenbrae

USC/Norris Comprehensive Cancer Center and Hospital

Tibotec Therapeutics - Division of Ortho Biotech Products, LP

Mather Veteran Affairs Medical Center

Mercy Cancer Center at Mercy Medical Center

Memorial Medical Center

Sutter Health - Western Division Cancer Research Group

University of California Davis Cancer Center

Saint Helena Hospital

California Pacific Medical Center - California Campus

Sutter Pacific Medical Foundation

Tahoe Forest Cancer Center

Sutter Solano Medical Center

University of Colorado Cancer Center at UC Health Sciences Center

Veterans Affairs Medical Center - Denver

Shaw Regional Cancer Center

Poudre Valley Hospital

Front Range Cancer Specialists

St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center

Montrose Memorial Hospital Cancer Center

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

Yale Cancer Center

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

George Washington University Medical Center

Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital

University of Florida Shands Cancer Center

Mayo Clinic - Jacksonville

Ella Milbank Foshay Cancer Center at Jupiter Medical Center

CCOP - Mount Sinai Medical Center

Northeast Georgia Medical Center

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Saint Luke's Mountain States Tumor Institute - Fruitland

Idaho Urologic Institute, PA

Mountain States Tumor Institute - Meridian

Saint Luke's Mountain States Tumor Institute

Mountain States Tumor Institute at St. Luke's

Rush-Copley Cancer Care Center

Illinois CancerCare - Bloomington

Graham Hospital

Illinois CancerCare - Canton

Illinois CancerCare - Carthage

Memorial Hospital

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Hematology and Oncology Associates

Decatur Memorial Hospital Cancer Care Institute

Eureka Community Hospital

Illinois CancerCare - Eureka

Evanston Hospital

St. Francis Hospital

Galesburg Clinic, PC

Illinois CancerCare - Cottage

Illinois CancerCare - Havana

Kellogg Cancer Care Center

Veterans Affairs Medical Center - Hines

Hinsdale Hematology Oncology Associates

Joliet Oncology-Hematology Associates, Limited - West

Provena St. Mary's Regional Cancer Center - Kankakee

Illinois CancerCare - Kewanee Clinic

La Grange Memorial Hospital

North Shore Oncology and Hematology Associates, Limited - Libertyville

Illinois CancerCare - Macomb

McDonough District Hospital

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Illinois CancerCare - Monmouth

Good Samaritan Regional Health Center

Hematology Oncology Consultants - Naperville

Cancer Care and Hematology Specialists of Chicagoland - Niles

BroMenn Regional Medical Center

Community Cancer Center

Illinois CancerCare - Community Cancer Center

Mid-Illinois Hematology-Oncology Associates at Community Cancer Center

Community Hospital of Ottawa

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Cancer Treatment Center at Pekin Hospital

Illinois CancerCare - Pekin

Proctor Hospital

CCOP - Illinois Oncology Research Association

Oncology Hematology Associates of Central Illinois, PC - Peoria

Methodist Medical Center of Illinois

Illinois CancerCare - Peru

Illinois Valley Community Hospital

Illinois CancerCare - Princeton

Hematology Oncology Associates - Skokie

Illinois CancerCare - Spring Valley

Regional Cancer Center at Memorial Medical Center

CCOP - Carle Cancer Center

Elkhart Clinic, LLC

Michiana Hematology-Oncology, PC - Elkhart

Elkhart General Hospital

Fort Wayne Medical Oncology and Hematology

Indiana University Melvin and Bren Simon Cancer Center

Veterans Affairs Medical Center - Indianapolis

Androgen Ablation Therapy With or Without Chemotherapy in Treating Patients With Metastatic Prostate Cancer

CHAARTED: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer

Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

manganese/atrofia

Adrenergic Blockers for Cardiac Changes in Early Parkinson's Disease

S100β and Neuron Specific Enolase Levels in Liver Transplantation

A Study to Determine if Aquamin Modulates Inflammatory Biomarkers in the Blood of Osteoarthritis and Healthy Subjects

Androgen Ablation Therapy With or Without Chemotherapy in Treating Patients With Metastatic Prostate Cancer

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