Behaviors and Mental Disorders

All Conditions

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Anxiety Disorders

Depression

Depressive Disorder

Dementia

Genetic Diseases, Inborn

Brain Diseases

Central Nervous System Diseases

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

All Drugs and Chemicals

Testosterone

Patients' records from institutional or national biobanks are reviewed.

Electronic Health Record Review

Kevin Nead

This study evaluates the association between testosterone levels and risk of dementia and adverse mental health outcomes (e.g. depression and anxiety). It is not known whether low testosterone levels may be associated with an increased risk of dementia. Learning about the association between testosterone levels and risk of dementia may help determine the long-term effects of androgen deprivation therapy and may help improve quality of life.

PRIMARY OBJECTIVE:

I. To use a Mendelian randomization study design to determine whether genetically predicted decreased testosterone levels are associated with an increased risk of dementia.

SECONDARY OBJECTIVE:

I. To examine whether genetically predicted decreased testosterone levels are associated with worse cognitive function and adverse mental health outcomes.

OUTLINE:

Patients' records from institutional or national biobanks are reviewed.

Evaluation of Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes

Evaluation of a Causal Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes: A Mendelian Randomization Analysis

Will utilize genetic variants associated with testosterone levels at genome-wide statistical significance thresholds (P \< 5 x 10-8) in published meta-analyses. Will additionally conduct a genome-wide association study with testosterone values in the UK Biobank. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).

Association between low testosterone levels and depression will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).

Association between low testosterone levels and anxiety will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).

Association between low testosterone levels and cognitive/mental health will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).

M.D. Anderson Cancer Center

Symptoms and General Pathology

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Syndrome

Lymphoma

Lymphadenopathy

Lymphoproliferative Disorders

Autoimmune Lymphoproliferative Syndrome

Neoplasms by Histologic Type

Lymphatic Diseases

Immunoproliferative Disorders

Autoimmune Diseases

Lymphosarcoma

Fluorodeoxyglucose F18

V. Koneti Rao, M.D.

This study will evaluate the usefulness of FDG-PET scanning in distinguishing autoimmune lymphoproliferative syndrome (ALPS) from lymphoma. Lymphoma is cancer of the lymph system. ALPS is a condition involving persistent enlargement of the lymph glands, spleen, or liver, and a range of other problems relating to blood cell counts and abnormal immune activity, in which the immune system attacks healthy tissues. People with ALPS particularly those with an abnormal Fas gene also have an increased risk of developing lymphoma. The Fas gene codes for a protein that causes immune cells called lymphocytes to die when they are no longer needed.

FDG-PET is a new nuclear imaging test that is very effective in detecting lymphoma. It is important to identify these cancers as quickly as possible, since some are very curable when caught early. Since ALPS and lymphoma share several common characteristics, a reliable, non-invasive method of distinguishing the two, such as FDG-PET might offer, is crucial. FDG-PET uses a radioactive sugar molecule to produce images that show the metabolic activity of tissues. Because cancer cells grow and divide more rapidly than normal cells, they metabolize more sugar for fuel. This increased activity identifies them as cancer in FDG-PET scanning. For this procedure, the subject is injected with the sugar molecule and lies in a doughnut-shaped machine (PET camera) for the imaging.

Adults and children 10 years old or older with ALPS, with or without lymphoma, may be eligible for this study. Candidates will be screened with a physical examination, blood tests, and computed tomography (CT) scan.

Participants will have an FDG-PET scan and a DEXA scan. The DEXA scan measures fat and non-fat tissue and is used help interpret the FDG-PET results. For this test, the subject lies on a table while a fast X-ray is taken from head to toe.

Patients who develop signs or symptoms suggesting the development or recurrence of lymphoma (such as further enlargement of lymph glands, unexplained fever or weight loss, or abnormal scans) may undergo a tissue biopsy. For this procedure, a small piece of lymph or other tissue is surgically removed for examination under the microscope. In addition, patients who develop these symptoms may be asked to undergo additional FDG-PET scans up to two a year in patients without lymphoma, and as many as needed in patients with lymphoma to evaluate their response to treatment and guide future therapy.

The Autoimmune Lymphoproliferative Syndrome (ALPS) is an inherited disorder associated with defective lymphocyte apoptosis, which is clinically characterized by prominent non-malignant lymphadenopathy, hepatosplenomegaly and overt autoimmune diseases such as hemolytic anemia, autoimmune thrombocytopenia and neutropenia. Additionally, ALPS patients have a significantly increased risk of developing non-Hodgkin's and Hodgkin's lymphoma.

The diagnosis of lymphoma is particularly troublesome in ALPS because many ALPS manifestations overlap with clinical features suggestive of lymphoma. Therefore, individuals with ALPS may undergo repeated biopsies during the course of the disease. Finding a non-invasive test that can predictably discriminate benign from malignant lymphadenopathy in ALPS, and that can help discern whether a more invasive lymph node biopsy is necessary, would be very desirable.

Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is an increasingly used non-invasive imaging technique for staging and monitoring therapeutic responses in patients with lymphoma. This technique might be able to assist us in distinguishing whether enlargement of lymph nodes is due to ALPS versus ALPS associated lymphoma. However, FDG-PET has not been studied in patients with ALPS. This study will first explore whether ALPS patients with lymphadenopathy show FDG uptake. If uptake is shown, the study will obtain initial quantitative data to compare FDG uptake in ALPS patients with lymphadenopathy, and ALPS patients with associated lymphoma. The ultimate goal is to assess FDG-PET as a reliable non-invasive method to differentiate lymphadenopathy due to ALPS versus that of ALPS associated lymphoma.

Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) to Evaluate Autoimmune Lymphoproliferative Syndrome (ALPS) and ALPS-associated Lymphoma

Study of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) for the Evaluation of the Autoimmune Lymphoproliferative Syndrome (ALPS) and ALPS-Associated Lymphoma

National Institute of Allergy and Infectious Diseases (NIAID)

Nutritional and Metabolic Diseases

Metabolic Diseases

Thymoglobulin

Antilymphocyte Serum

Immunologic Factors

Immunosuppressive Agents

Thymoglobulin 7.5 mg/kg/course prior to HSCT

Thymoglobulin 2.5 mg/kg of body weight IV administered daily for 3 days prior to HSCT.

Thymoglobulin infused over a minimum of 6 hours for the first infusion and over at least 4 to 6 hours on subsequent days of therapy.

Thymoglobulin (rATG)

Tal Schechter-Finkelstein, MD

This study will describe the pharmacokinetic disposition of biologically active rabbit anti-thymocyte globulin (rATG) after a consistent dose of 7.5 mg/kg/course given as part of the conditioning regimen in children undergoing hematopoeitic stem cell transplantation (HSCT).

Allogeneic hematopoeitic stem cell transplantation (HSCT) is a therapeutic option for patients with malignancies as well as metabolic and genetic diseases. Conditioning regimens given prior to donor cell infusion aim to ablate the recipient bone-marrow, to allow engraftment of the stem-cells infused, and to prevent acute versus host disease (aGVHD). Anti-thymocyte globulin (ATG) is one of the immunosuppressive drugs given as a preparative regimen for HSCT. Subjects will be given an ATG infusion daily for 3 days prior to HSCT and serum levels will be collected, as per schedule, with the last sample taken +100 days post-HSCT.

Pharmacokinetics of Thymoglobulin in Paediatric Haematopoietic Stem-cell Transplants

Pharmacokinetics and Pharmacodynamics of Thymoglobulin in Paediatric Haematopoietic Stem-cell Transplant Recipients

ATG pharmacokinetic parameters were estimated using a noncompartmental model. Maximum Observed Concentration (Cmax) of ATG After a 7.5 mg/kg/Course was measured

The Hospital for Sick Children

Staff Physician

This is a pharmacokinetic study. There was no risk for the patients for measuring drug levels.

Adverse Events were not monitored/assessed for this study.

Thymoglobulin 7.5 mg/kg/course prior to HSCT

Thymoglobulin (rATG): Thymoglobulin 2.5 mg/kg of body weight IV administered daily for 3 days prior to HSCT.

Thymoglobulin infused over a minimum of 6 hours for the first infusion and over at least 4 to 6 hours on subsequent days of therapy.

Age, Categorical

Sex: Female, Male

Dr Tal Schechter-Finkelstein

Blood samples for ATG concentration determination were obtained at 0, +1, +4, +7, +14, +28, +60, +75 and +100 days post-HSCT. ATG serum concentrations were analyzed using a validated immunoassay. ATG pharmacokinetic parameters were estimated using a noncompartmental model. The relationship between HSCT outcomes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes	NCT04743466	Anxiety Disorde... Depression Genetic Disorde... Hematopoietic a... Malignant Solid...	Electronic Heal...	-	M.D. Anderson Cancer Center
Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) to Evaluate Autoimmune Lymphoproliferative Syndrome (ALPS) and ALPS-associated Lymphoma	NCT00068146	Lymphoprolifera... Lymphoma		8 Years -	National Institutes of Health Clinical Center (CC)
Pharmacokinetics of Thymoglobulin in Paediatric Haematopoietic Stem-cell Transplants	NCT01135537	Malignancy Metabolic Disea... Genetic Disorde...	Thymoglobulin (...	- 21 Years	The Hospital for Sick Children

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