Clinical Research Directory

Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders

This basket trial will enroll prepubertal children and adolescents with clinically diagnosed and genetically confirmed (if applicable) TS, SHOX-D, SGA, or ISS between ages of ≥2 and \<18 years with open growth plates. The purpose of the study is to see how well treatment with once-weekly lonapegsomatropin works compared to treatment with daily somatropin. Approximately 186 participants will be distributed equally (1:1), to receive either lonapegsomatropin for 2 years or somatropin for 1 year followed by lonapegsomatropin for 1 year. This trial will be conducted in the United States, France, Germany, Italy, Romania, Spain and South Korea.

Cryopreservation of Ovarian Cortex in Girls With Turner Syndrome

Ovarian insufficiency is common in Turner syndrome related to premature and rapid follicular apoptosis and spontaneous pregnancies are rare in this population. Ovarian cryopreservation has been used in an effort to preserve fertility in patients undergoing treatments which lead to premature and severe ovarian insufficiency. This study aims to assess the relevance of ovarian tissue cryopreservation in girls with Turner syndrome. Based on ovarian follicular density as primary outcome and karyotypic, clinical and hormonal markers as secondary outcomes, analysis of the study will allow to select the patients to whom the procedure would benefit the most.

Natural History of Noncirrhotic Portal Hypertension

Background: \- Noncirrhotic Portal Hypertension (NCPH) is caused by liver diseases that increase pressure in the blood vessels of the liver. It seems to start slowly and not have many warning signs. Many people may not even know that they have a liver disease. There are no specific treatments for NCPH. Objectives: \- To learn more about how NCPH develops over time. Eligibility: \- People age 12 and older who have NCPH or are at risk for getting it. In the past year, they cannot have had other types of liver disease that typically result in cirrhosis, liver cancer, or active substance abuse. Design: * Participants will have 2 screening visits. * Visit 1: to see if they have or may develop NCPH. * Medical history * Physical exam * Urine and stool studies * Abdominal ultrasound * Fibroscan. Sound waves measure liver stiffness. \<TAB\>- Visit 2: * Blood tests * Abdominal MRI * Echocardiogram * Questionnaire * Liver blood vessel pressure (hepatic venous portal gradient (HVPG)) measurement. This is done with a small tube inserted in a neck vein. * They may have a liver biopsy. * All participants will visit the clinic every 6 months for a history, physical exam, and blood tests. They will also repeat some of the screening tests yearly. * Participants with NCPH will also have: * Upper endoscopy test. A tube inserted in the mouth goes through the esophagus and stomach. * At least every 2 years: Esophagogastroduodenoscopy. * At least every 4 years: testing including HVPG measurements and liver biopsy. * Participants without NCPH will also have: * Liver biopsy and HVPG measurements to see if they have NCPH. * Every 2 years: abdominal MRI and stool studies. * The study will last indefinitely.

Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy

Background: Turner Syndrome, galactosemia, and premature ovarian insufficiency are all conditions that may make it very hard or impossible for a person to become pregnant and have their own child. Researchers want to learn more about why this happens and if freezing Gonadal tissue allows for fertility preservation. Objective: To find out why people with certain conditions have can have premature ovarian insufficiency (POI or early menopause) and individuals with variations in sex characteristics have trouble getting pregnant and if freezing the gonads tissue from them will help to have their own child in the future. Eligibility: Individuals aged 2-21 who have Turner Syndrome or galactosemia. Also, females aged 13-21 with premature ovarian insufficiency, individuals with variations in sex characteristics, and individuals 2-35 receiving high-risk gonadotoxic therapy Design: Participants will be screened with a medical history. Participants may have a physical exam and blood tests. Their body measurements may be taken. These include weight, height, arm span, skin fold, and sitting height. They may fill out surveys about their quality of life, body image, and health. Participants may have a transabdominal pelvic ultrasound. A probe will be placed on their belly and will take pictures of the organs in the pelvis. They may have a transvaginal pelvic ultrasound performed while asleep in the operating room if needed. Participants may have surgery to remove an gonads and skin biopsy. The removed tissue will be frozen and stored. The tissue will have to be stored for many years. NIH will pay to store the tissue for 1 year. After that, participants will have to pay for storage. A piece of the gonads (no more than 20%) will be used for research Travel, lodging and meals for participants traveling greater than 50 miles will be reimbursed based off the government rate. Local participants will not be reimbursed. Participants will have a checkup 6 weeks after surgery one or more follow-up visits 6-18 months after surgery. They may have phone follow-up every 12-24 months after surgery. Participation will last 30 years.

A Basket Study of Vosoritide in Children With Turner Syndrome, Short Stature Homeobox-Containing Gene Deficiency, and Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment

The purpose of this basket study in children with Turner syndrome, SHOX deficiency, and Noonan syndrome is to evaluate the effect of 3 doses of vosoritide on growth as measured by AGV after 6 months of treatment. The long-term efficacy and safety of vosoritide at the therapeutic dose will be evaluated up to FAH.

Pathogenetic Basis of Aortopathy and Aortic Valve Disease

The main purpose of this study is to define the complex genetic and pathogenic basis of thoracic aortic aneurysm (TAA) and other forms of aortopathy and/or aortic valve disease by identifying novel disease-causing genes and by identifying important genetic modifiers for aortic and aortic valve disease severity.

A Study Comparing Different Treatment Approaches for the Initiation of Puberty in Girls With Turner Syndrome Using a TRIFECTA-DARED Approach for Rare Diseases

Turner syndrome is a condition in which a girl's body does not make enough estrogen on its own, so doctors give estrogen to help start breast and uterine (womb) development. Hence, the goal of this clinical trial is to learn whether two different ways of giving estrogen help girls and young women with Turner syndrome go through puberty normally, and to compare how well each method works and how safe they are. The main questions the trial aims to answer are: 1. Does taking an oral estrogen tablet (Progynova) or applying an estrogen gel (Oestrogel) lead to better breast development? 2. Does one method lead to a larger uterine size as seen on ultrasound? 3. Do participants start menstrual-like (withdrawal) bleeding, and does one method cause it sooner? 4. What side effects (for example, headaches, nausea, changes in blood tests) happen with each method? Who can take part? * Girls and young women aged 11-30 years with a confirmed diagnosis of Turner syndrome and no previous estrogen treatment. * They have not yet begun puberty (no breast growth, and a small uterus on ultrasound). * They agree to adhere to the study schedule and keep a diary of any bleeding or side effects What will happen to the participants during the clinical trial? * Get assigned at random to one of two groups (1:1 ratio): 1. Gel group: Apply Oestrogel (17β-estradiol) to the skin, starting twice a week, then daily with increasing doses over 19 months. 2. Tablet group: Swallow Progynova (estradiol valerate) tablets, starting twice a week, then daily with increasing doses over 19 months. * Visit the clinic at the start of study (baseline), month 1, 7, 13, and 19 for: 1. A physical exam (including breast staging). 2. An ultrasound to measure uterine length and thickness. 3. A blood test for safety checks (triglycerides and other markers). 4. Keep a diary noting any spotting or bleeding (called withdrawal bleeding) and any side effects. Why does this matter? Girls and young women with Turner syndrome often need estrogen to begin puberty safely. This trial will show which method-gel or tablets-best mimics natural puberty (breast and uterine growth), how quickly menstrual-like bleeding begins, and which has fewer unwanted effects. The findings will help doctors choose the most effective and safe treatment for people with Turner syndrome.

Genetic and Epigenetic Background of Inner Ear Dysfunction in Turner Syndrome

The goal of this case-control study is to pave the way for new revolutionary treatment measures within hearing loss that could either replace or delay the need for hearing aids. The study focuses on people with Turner syndrome (TS). The aim is to find out if there are specific DNA methylation patterns and/or RNA expression profiles linked to sensorineural hearing loss (SNHL) in people with TS. Additionally, the structure and function of the inner ear in these individuals will be examined to see if there is a connection to their epigenetic profile. The main question it aims to answer is: Does epigenetics constitute a common denominator for some of the unexplained SNHL cases? Turner Syndrome (TS) represents an ideal model for studying epigenetics related to sensorineural hearing loss (SNHL). Participants will undergo the following tests: * Ear examinations * Hearing tests * Balance tests * Blood tests * MRI scans * CBCT (cone-beam computed tomography) scans

Parental Project Amongst 93 Patients With Turner Syndrome

The aim is to describe the parental project, spontaneous pregnancies and pregnancies resulting from egg donation or adoption in women diagnosed with Turner syndrome treated at Strasbourg University Hospitals.

A Trial to Investigate Different Doses of Lonapegsomatropin Compared to Somatropin in Individuals With Turner Syndrome

A 104 week dose finding open label trial followed by an optional 78 week open label extension of lonapegsomatropin, a long-acting growth hormone product, administered once-a-week versus daily somatropin product in prepubertal individuals with Turner syndrome. Approximately 48 individuals (12 individuals per arm) will be randomized to receive one of three doses of lonapegsomatropin or a daily injection of somatropin. This is a trial that will be conducted in the United States.

A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9

The purpose of this study is to find out if somapacitan is safe and how well somapacitan works in children either born small for gestational age or with Turner syndrome, Noonan syndrome or idiopathic short stature. Somapacitan is a new growth hormone medicine for treatment of low level of growth hormone. The study will last for about 3 years. During the study, the participants will be treated with somapacitan once a week. Somapacitan can be injected anytime during the day. The study doctor or nurse will show how to inject somapacitan, so that the participant knows how to do it at home.

Bleeding Patterns in Sequential and Continuous Progesterone Supplementation in Adolescents With Turner Syndrome

This is a single-site open label non-randomized study comparing effects of sequential versus continuous use of progesterone supplementation amongst Turner Syndrome (TS) patients with primary ovarian insufficiency (POI) prescribed hormone replacement therapy (HRT).

Parent and Infant Inter(X)Action Intervention (PIXI)

The objective is to develop and test, through an iterative process, an intervention to address and support the development of infants with a confirmed diagnosis of a neurogenetic disorder with associated developmental delays or intellectual and developmental disabilities. The proposed project will capitalize and expand upon existing empirically based interventions designed to improve outcomes for infants with suspected developmental delays. Participants will be infants with a confirmed diagnosis of a neurogenetic disorder (e.g., fragile X, Angelman, Prader-Willi, Dup15q, Phelan-McDermid, Rhett, Smith Magenis, Williams, Turner, Kleinfelter, Down syndromes, Duchenne muscular dystrophy) within the first year of life and their parents/caregivers. The intervention, called the Parent and Infant Inter(X)action Intervention (PIXI) is a comprehensive program inclusive of parent education about early infant development and the neurogenetic disorder for which they were diagnosed, direct parent coaching around parent-child interaction, and family/parent well-being support. The protocol includes repeated comprehensive assessments of family and child functioning, along with an examination of feasibility and acceptability of the program.

Role of Cardiac AngioMR in Diagnosis of Cardiac and Vascular Anomalies in Adult Patients with Turner Syndrome

Considering the high prevalence of cardiovascular disease in Turner syndrome patients, noninvasive cardiac imaging is crucial for diagnosis and follow-up. From the review of the literature, it was evident that the imaging techniques used involved the evaluation of only the thoracic findings, in particular the heart and the thoracic aorta, while no data are currently available on the distal abdominal aorta or iliac arteries, since ultrasound and MRI are interrupted at the diaphragmatic level.

Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome

Rationale: Infertility due is a major concern for girls with Turner syndrome (TS) and their parents. Physicians are often asked about possible options to preserve their fertility. However, despite some experimental case reports, clear evidence for fertility preservation in these girls is lacking and many questions remain. Without evidence on the effectiveness of fertility preservation it cannot routinely be offered to girls with TS. Objective: To investigate the occurrence of live birth in women with TS after ovarian tissue cryopreservation in childhood followed by auto transplantation in adulthood. Study design: A national multicentre exploratory intervention study Study population: Girls diagnosed with Turner Syndrome, aged 2-18 years. Intervention: Ovarian tissue cryopreservation in childhood followed by auto transplantation in adulthood. In order to obtain the ovarian tissue for cryopreservation, all girls must undergo a laparoscopy under general anaesthesia which will be performed in academic/university clinics with paediatric surgery. During the laparoscopic intervention, a unilateral oophorectomy will be performed, thereby leaving the other ovary intact for hormone production, ovulation, spontaneous pregnancies and as an auto transplantation site for cryopreserved-thawed ovarian cortical tissue later on. Furthermore, a small sample of the ovarian cortex will be used to assess the oocyte quality and genetics (e.g. the presence of germ line mosaicism). Oocytes will be karyotyped by using Fluorescence in situ hybridization (FISH). Karyotypic and hormonal data will be collected once at the yearly clinical visit at the paediatric-endocrinologist. Therefore, a buccal swab and one extra blood sample will be taken and evaluated during the routine laboratory evaluation. In the future, auto transplantation of frozen-thawed ovarian cortex strips will be performed.

Characterization of Hepatopathy in Turner Syndrome: Analysis of Determinants

The present study is therefore aimed at investigating the prevalence of hepatic alterations (laboratory and imaging) in adult patients with TS and generating hypothesissto the possible etiopathogenetic factors most involved, as well as evaluating the correlation between biochemical and structural abnormalities. Thus, the study could provide relevant etiopathogenetic and prognostic results on the development of hepatopathy in TS patients.

Cardiopulmonary Exercise Testing in Girls (8-18y) with Turner Sydrome.

The goal of this clinical trial is to have a beter insight in the exercise tolerance in girls with Turner Syndrome aged 8-18 years . The main question it aims to answer is: Is there a difference in VO2 max comparing Turner syndrome girls with standard values? How do cardiovascular parameters change during exercise (heart rate, bloodpressure, ...) Participants will perform a cyclo-ergometry in a standardised way.

Neuropsychological Assessment of Children and Adolescents With Turner Syndrome

Turner syndrome (TS) is a rare chromosomal disorder characterized by partial or complete loss of one of the X chromosomes that affects about one in every 2000 female babies born. These young patients described difficulties making friends, understanding others' emotions and intentions, and controlling their own emotions. Difficulties in these domains could led to social withdrawal, to reduced social skills and could have a significant impact on self esteem and mental health as well as on long-term academic and social functioning in affected individuals. The purpose of this project is to identify functional and dysfunctional cognitive and socio-cognitive abilities in these young patients which could account social difficulties described by some of them and their family. To this end, 35 girls with TS and 35 girls with isolated growth hormone deficiency and normal cerebral MRI will be recruited. Subjects will be 7 to 16 years and 11 months of age. Socio-cognitive and cognitive functions will be assessed with neuropsychological and experimental tasks. Questionnaires completed by patient, parents or teacher, will evaluate social and behavioral functioning.

Inspiring New Science In Guiding Healthcare in Turner Syndrome Registry

INSIGHTS is a registry research study that collects key information on medical history for girls and women with Turner syndrome and the clinical care they receive. This includes genetic tests, imaging, medications, and more for hundreds of patients seen at a number of clinics across the US. In addition to learning a lot about the current state of health for individuals with TS, INSIGHTS serves as an infrastructure to conduct future studies are meaningful to patients and their families.

Long Term Effects of Oral Versus Transdermal Estrogen Replacement Therapy in Turner Syndrome

This 14-month, phase IV, randomized controlled crossover trial aims to compare the effects of oral versus transdermal estrogen replacement therapy (ERT) in women with Turner syndrome (TS). The study's objectives are to clarify endocrine, metabolic, cardiovascular, and thromboembolic risk factors in TS after a wash-out period without estrogen (E2) treatment; compare the effects of oral versus transdermal (TD) ERT regimens; and examine the long-term effects of E2 administration via these two routes. The study involves 50 TS women aged 18-50 years and 50 control participants. TS participants are randomized to receive either oral or TD ERT for six months, followed by crossover to the alternate treatment for another six months. Prior to randomization, any existing ERT will be discontinued for a 1-month washout period. A second 1-month washout period will occur between the two 6-month treatment phases. Laboratory analyses and clinical investigations are performed after the first wash-out period, after the first six months of treatment, and after the last six months of treatment. We anticipate that this study may provide a basis for new and improved recommendations for sex hormone replacement therapy in TS.

Determining Dose Equivalence Between Oral and Transdermal Estrogen Treatment in Women With Turner Syndrome

This 5-week, phase IV randomized crossover trial aims to compare the effects of oral versus transdermal estrogen replacement therapy (ERT) in women with Turner syndrome (TS). The objective is to establish the equipotency between the two estradiol regimens by evaluating various estradiol-dependent surrogate markers. The study involves 50 women with TS, aged 18-50 years, who are randomized to receive either oral or transdermal ERT for 14 days, followed by a crossover to the alternate treatment for another 14 days, with a one-week washout period in between. Blood tests are conducted at baseline, after the first 14 days of treatment, after the washout period, and after the final 14 days of treatment. The investigators anticipate that this study will provide clinicians with a better understanding of ERT in treating women with TS.

Vosoritide for Short Stature in Turner Syndrome

Turner syndrome (TS) is characterized by a missing whole or part of the second sex chromosome in a phenotypic female, resulting in short stature due to haploinsufficiency of the short-stature homeobox-containing (SHOX) gene. Growth hormone (GH) is an approved therapy for this condition, although not associated with GH deficiency, and benefits are modest. Vosoritide, a C-type natriuretic peptide (CNP) analog, targets chondrocytes within the growth plate leading to increased cell proliferation and hypertrophy. We hypothesize that patients with TS and short stature will respond to vosoritide treatment leading to increased growth velocity. This study will enroll pre-pubertal girls with TS who are either naïve to GH or have had a poor response to GH therapy. All subjects will be treated with vosoritide for 12 months and will be assessed for safety monitoring and improvement in height outcomes. Annualized growth velocity (AGV) on vosoritide will be compared to AGV in the 6-18 months prior to initiation of vosoritide based on historical data available in the medical record. Subjects with a positive response to therapy will be given the option to continue in the extension phase of the study during which they will continue to receive vosoritide until growth cessation.

The Danish TURNER Cryopreservation Study

The goal of this clinical trial is to investigate if cryopreservation of ovarian tissue in girls with Turner syndrome can improve their fertility and lead to increased number of liveborn babies of Turner syndrome mothers. Women with Turner syndrome suffer from premature ovarian insufficiency which leads to infertility and lack of estrogen. The main questions it aims to answer are: * Does the number of pregnancies and liveborn children increase after cryopreservation of ovarian tissue in turner syndrome? * Is the possible to predict when a girl with Turner syndrome reach menopause using monitoring of sex hormones? * Is it possible to identify any genes causing ovarian failure in Turner syndrome females? Participants between 2-18 years old will be asked to participate in a laparoscopic surgery and removal of one ovary in order to cryopreserve the tissue until adulthood. The the cortical tissue will be autotransplanted in order to preserve fertility. The participant will during the study period be monitored using sex hormones. Furthermore, the investigators wish to investigate the ovarian tissue using RNA sequencing and DNA methylation analysis. No comparison group is present.

Lymphedema, Low-grade Inflammation and the Vasculature in Turner Syndrome

100 women with karyotype verified TS, previously examined at 4 study visits during a 19-year period will be asked to participate in a 5th study visit. Healthy age-matched females will be included as controls in a ratio 2:1. The aim is to examine and quantify the cardiovascular and lymphatic system in women with TS. The investigators will study a possible causal mechanism between the known pathologic phenotype and alterations in these systems to understand, prevent or treat the life-threatening complications in TS.