Klinefelter Syndrome

Researchers are evaluating the use of XYOSTED as a testosterone replacement therapy in adolescent males aged 12 to under 18 years with primary or secondary hypogonadism, a condition where the body produces little or no testosterone. This Phase 3/4 open-label study aims to assess how well XYOSTED supports the continuation or start of puberty, along with its safety and the testosterone levels it maintains. Participants will receive XYOSTED injections at doses tailored to their weight and targeted pubertal stage. Dose adjustments will be made based on testosterone levels measured at specific intervals after dosing, with evaluations approximately every three months to reach the desired hormone levels. After completing the 52-week initial study period, participants may enter a 24-month extension to further monitor long-term safety and treatment effects. Throughout the study and extension, participants will undergo clinical examinations including pubertal staging, blood tests for testosterone and other labs, bone density scans, body composition assessments, and X-rays to monitor bone age. Researchers will track changes in puberty progression, bone health, body measurements, and hormone levels. Participants will attend regular clinic visits every six months during the extension phase to continue safety and pharmacokinetic evaluations.

Myelodysplastic syndromes (MDS) are chronic blood disorders marked by ineffective blood cell production and normal marrow richness. This research aims to understand the biological and clinical aspects of MDS, including its progression to acute leukemia, which occurs in 30 to 40% of cases. The study focuses on the genetic and molecular diversity of MDS and seeks to identify markers predicting disease progression through a biocollection. The study involves collecting and analyzing biological material from patients diagnosed or suspected of having MDS. It explores three key scientific projects: splicing abnormalities related to SF3B1 mutations, the role of chromosomal deletions such as 5q affecting splicing genes RBM22 and SLU7, and the progression of MDS to acute myeloid leukemia by studying the clonal architecture of malignant cells. These projects use advanced genetic and molecular analysis techniques to deepen understanding of MDS mechanisms. Participants provide biological samples and clinical data, which are used for detailed genetic and functional studies. The study monitors patients over time to observe disease evolution and identify prognostic markers. The primary outcome is an epidemiologic study of the MDS patient cohort over five years. Participation includes consenting to data and sample collection, enabling researchers to analyze molecular changes and better understand MDS progression and prognosis.

Researchers are evaluating whether testing embryos for chromosomal abnormalities, called aneuploidy, can help select embryos more likely to result in a healthy live birth. This study focuses on embryos from assisted reproductive technology (ART) that are already undergoing genetic testing for monogenic disorders (PGT-M). The goal is to see if preimplantation genetic testing for aneuploidy (PGT-A) can reduce miscarriages and improve the chance of healthy births by avoiding embryos unlikely to succeed. This observational study does not introduce new treatments but collects data on aneuploidy from embryo biopsies and the spent culture media, the fluid in which embryos grow. Both sources of DNA will be analyzed to predict whether embryos will lead to live births. The study will compare these predictions to actual clinical outcomes, assessing the positive predictive value (how often embryos predicted to succeed do so) and the negative predictive value (how often embryos predicted to fail do not result in live birth). Participants will undergo standard care with PGT-M biopsies, and additional samples may be collected before and after birth for further validation, including chorionic villus sampling, amniocentesis, fetal cells from maternal blood, and newborn DNA, though these are optional. Live birth data will be collected up to 10 months after embryo transfer. About 220 patients and 540 embryo transfers will be involved, with recruitment expected to take two years. The study aims to provide evidence on whether PGT-A should be used in clinical practice.

Researchers are investigating the impact of testosterone undecanoate compared to a placebo on reducing liver fat in overweight or obese men who have type 2 diabetes or prediabetes along with low testosterone (hypogonadism). This condition may contribute to metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD), which are increasing worldwide and linked to insulin resistance and fat buildup in the liver. The study also explores the role of testosterone in glucose metabolism and heart health in this high-risk group. Participants receive either intramuscular injections of testosterone undecanoate (1000mg/4ml) at the start, after 6 weeks, and then every 10 weeks for a total of 52 weeks, or a similar placebo injection on the same schedule. After this 52-week randomized, quadruple-blind phase, an additional open-label extension lasting 108 weeks will follow to examine long-term effects on cardiometabolic health. The study measures changes in liver fat, visceral fat, pancreatic fat, myocardial fat, glycemic control, and cardiovascular safety. During the study, participants undergo regular assessments including body measurements, blood tests for insulin sensitivity, HbA1c, lipid levels, blood pressure, and questionnaires on quality of life, sexual function, and diabetes management satisfaction. Imaging scans evaluate fat content in various organs and heart perfusion. Safety is closely monitored throughout both study phases. Total participation may last up to three years, combining the initial treatment and the extension period.

Researchers are studying endothelial dysfunction in men aged 30 to 50 who have vasculogenic erectile dysfunction (ED) confirmed by penile Doppler ultrasound. The study also investigates changes in endothelial function in men with hypogonadism before and after they begin testosterone therapy. The research aims to better understand how endothelial function is affected by ED and hormonal treatment and to fill gaps regarding the effects of PDE5 inhibitors and testosterone therapy on vascular health. Participants are divided into three groups: one group of men with vasculogenic ED receiving daily low-dose phosphodiesterase type 5 (PDE5) inhibitor therapy, a second group of hypogonadal men receiving testosterone therapy following clinical guidelines, and a third group of men with vasculogenic ED who receive no intervention. Endothelial function is measured using the EndoPAT device at the start of the study and again at 3 and 6 months after treatment begins or baseline for the no-intervention group. Throughout the study, participants undergo assessments of endothelial function by Reactive Hyperemia Index (RHI) using EndoPAT, as well as evaluations of cardiovascular health markers, sexual function scores, and monitoring for adverse events at baseline and at 3 and 6 months follow-ups. The study is non-randomized and open-label, with a total participation duration of 6 months to evaluate changes over time in endothelial and cardiovascular health linked to ED and hormonal therapy.

Researchers are evaluating how advanced treatments for male patients with non-small cell lung cancer (NSCLC) affect sexual health and hormone levels. The study focuses on assessing the incidence of endocrine toxicity and sexual dysfunction, including erectile dysfunction, in men undergoing active cancer treatment. This research highlights an important but often overlooked aspect of quality of life in oncology, especially for younger patients receiving targeted therapies, immunotherapy, or chemotherapy. The study includes male patients with advanced or metastatic NSCLC who are actively receiving various anticancer treatments. Participants are grouped based on their cancer subtype and treatment type, including targeted drugs such as Alectinib, Brigatinib, Lorlatinib, Osimertinib, Sotorasib, Dabrafenib, Trametinib, and Selpercatinib, immunotherapy agents like Pembrolizumab, Cemiplimab, and Nivolumab, and chemotherapy drugs including Carboplatin, Pemetrexed, and Paclitaxel. Treatment dosages and schedules vary, with some drugs taken daily and others administered intravenously every 14 to 21 days. Participants will be monitored from the start of treatment for up to one year to track the occurrence of sexual dysfunction, hypogonadism, and erectile dysfunction. The study involves collecting patient-reported outcomes and laboratory assessments to measure these effects. Male patients must be sexually active prior to treatment and have good performance status. The trial is observational, with no placebo or control group, and aims to provide comprehensive data on how anticancer treatments impact male sexual health during therapy.

Researchers are evaluating the safety and effectiveness of stem cell or stem cell-derived exosome therapy for people with gonadal failure, which includes testicular failure, hypogonadism, ovarian insufficiency, and premature ovarian failure (POF). The study focuses on adults aged 20 to 50 who have not responded well to usual treatments like hormone replacement therapy or assisted reproductive technologies. It aims to explore whether this regenerative treatment can restore hormone production and improve reproductive function, especially in a region where donor sperm and eggs are not allowed. Participants will receive a single injection of adipose-derived stem cells or exosomes directly into their testes or ovaries under anesthesia. The stem cells or exosomes are prepared in a specialized lab and checked for safety and quality before administration. This open-label pilot study includes 60 participants, divided equally between men and women. Follow-up visits occur at 3, 6, 9, and 12 months after treatment to track changes in hormone levels, gonadal function, and reproductive capacity. During the study, participants will have blood tests to measure hormones like testosterone and estradiol, imaging scans to assess gonadal tissue, and semen analysis for men. Researchers will monitor for any side effects or complications, including infections or immune reactions. The main outcome is the change in reproductive capacity after 12 months. Data collected will help guide future larger trials and contribute to developing new fertility treatments using regenerative medicine.

Researchers are conducting the GALAXY Registry study to learn more about individuals with X and Y chromosome variations, also known as sex chromosome aneuploidies. This observational study aims to collect detailed information from medical records of hundreds of patients seen at various clinics across the United States. The goal is to improve health outcomes and the care provided to people with these genetic variations. The study does not involve any treatment or intervention. Instead, it gathers data such as genetic test results, imaging, medications, and other health information over time. The registry collects this data longitudinally, following participants for up to 15 years to observe the development of various health conditions. Participants provide access to their medical records, and researchers track the occurrence of health conditions, including mental health diagnoses, obesity, dyslipidemia, hypertension, hypothyroidism, hyperthyroidism, and diabetes. The study monitors these outcomes from the start and continues for up to 15 years. Participants of all ages and genders can join, and the study includes regular data collection without requiring additional treatments or procedures.

Researchers are studying fertility challenges in individuals with Turner Syndrome, galactosemia, premature ovarian insufficiency (POI), and variations in sex characteristics. The study aims to understand why these conditions lead to early loss of ovarian function and whether freezing gonadal tissue can help preserve fertility for future use. The investigation includes examining the number and quality of follicles and gametes in the tissue and exploring the underlying biological reasons for follicle loss using advanced genetic sequencing techniques. Participants include children and adolescents aged 2 to 35 years who meet various condition-specific criteria. They may undergo medical history screening, physical exams, blood tests, body measurements, and ultrasound imaging. Some participants will have surgery to remove gonadal tissue, which will be frozen and stored for fertility preservation and used for research. The tissue storage is funded by NIH for one year, after which participants may be responsible for ongoing costs. Follow-up care includes checkups six weeks after surgery and periodic visits or phone calls for up to 30 years. During the study, participants will complete surveys about quality of life and health, and researchers will track hormone levels and analyze tissue samples before and after freezing. The study will monitor surgical outcomes and long-term effects of tissue freezing. Researchers will also develop a national database to better understand outcomes and explore treatments to improve follicle preservation. Participation involves extensive evaluations, long-term follow-up, and contributes to advancing knowledge on fertility preservation in these conditions.

Researchers are studying adults with rare and complex genetic syndromes that affect multiple body systems and often include intellectual disability. These patients typically receive specialized care from multiple specialists during childhood, but as medical advances have extended life expectancy, many are now living into adulthood. The study aims to understand the medical needs, comorbidities, medication use, and quality of life impacts for adults with these rare syndromes, addressing a gap in adult care and guidelines. This research involves a retrospective review of medical files, including medical history, laboratory results, additional tests, and records of physical and psychological complaints. There is no active treatment or intervention, as the study collects and analyzes existing data to gain insights about health issues and medication adaptations needed for these syndromes. Participants' medical records will be analyzed to evaluate the presence of physical health problems, laboratory values, physical and psychological complaints, and medication use over a one-year period. The study uses statistical software for analysis and aims to improve understanding of adult care needs for these rare genetic conditions. The study began in October 2018 and will continue through January 2030.