Clinical Research Studies at NICHD 2025

NICHD’s DIR leads numerous clinical protocols; visit https://www.clinicaltrials.gov/search?term=nichd for a complete listing of NICHD clinical trials. The following describes selected DIR clinical trials that are actively recruiting participants and provide contact information for the investigator(s) conducting those studies. For detailed information on all related research projects, please review the listed investigator’s section of the annual report.

Developmental Endocrinology, Metabolism, Genetics, and Endocrine Oncology

• Research on characterization of dysmorphology subjects with Creatine Transport Deficiency CTD. This study characterizes the shared facial phenotypes in pediatric patients with creatine transporter deficiency (CTD). Analysis of patient photographs by a dysmorphology expert aims to define a distinct facial profile. The objective is to establish these traits as a diagnostic aid to facilitate the early identification of individuals with CTD. Contact Laverne Mensah, M.D. at laverne.mensah@nih.gov or 301-496-8368.

• Patient-oriented research into etiology, pathophysiology, genetics, diagnosis, localization, and treatment of pheochromocytoma and paraganglioma. This research on pheochromocytoma and paraganglioma (PPGL) aims to increase understanding of these diagnoses and improve disease management for children and adults with these disorders. The study is identifying PPGL-associated genes with the aim to improve diagnostic capabilities. Lastly, bench-level studies include tumor pathology and chemistry research, designed to aid in the development of new clinical therapies. Contact Catherine Gordon, M.D.,M.S. at catherine.gordon@nih.gov, Alberta Derkyi, DNP or Ms. Sara Talvacchio, RN at ppglgroup@mail.nih.gov.

• Research on endocrine, genetic, and other pediatric disorders associated with endocrine and other tumors, which may affect the pituitary and other related organs. This observational study investigates the genetic underpinnings of pituitary and hypothalamic tumors. Through the collection and molecular analysis of patient biospecimens, the research aims to elucidate the developmental pathways contributing to oncogenesis. The study also evaluates the cognitive, psychological, and patient-reported health outcomes associated with these conditions, particularly in pediatric patients, to improve diagnosis and guide the development of future therapeutic strategies. Contact Deborah Merke, M.D., M.S. at dmerke@nih.gov. Research investigating the long-term effects of Cushing disease in childhood. Contact Deborah Merke, M.D., M.S. at dmerke@nih.gov.

• Evaluation of patients with endocrine disorders associated with excess androgen, including different forms of congenital adrenal hyperplasia. This longitudinal study characterizes the long-term effects of hypercortisolemia in survivors of pediatric Cushing's Disease. Following patients for up to 20 years post-cure, the research evaluates the persistence of endocrine, metabolic, cardiovascular, and neurocognitive abnormalities. The primary goal is to define the life-long health sequelae, using metrics like BMI z-score, to improve future monitoring and treatment strategies for this population. Contact Deborah Merke, M.D.,M.S. at dmerke@nih.gov, Amy Moon at amy.moon@nih.gov, or Lee Ann Keener at leeann.keener@nih.gov or 240-858-9033.

• Studies of genetic disorders related to altered cholesterol metabolism, including Smith-Lemli-Opitz syndrome (SLOS) and Niemann-Pick Disease, type C (NPC). This natural history study investigates Smith-Lemli-Opitz Syndrome (SLOS) and related inborn errors of cholesterol metabolism. By collecting longitudinal clinical data and biospecimens from affected individuals and carriers, the research characterizes the genetic, biochemical, and phenotypic aspects of these disorders. The primary objective is to define comorbidities and identify outcome measures to facilitate future therapeutic trials. For SLOS studies, contact Forbes Porter, M.D., PhD. at fdporter@mail.nih.gov or. For NPC studies, contact Desiree Labor, NP at desiree.labor@nih.gov or Derek Alexander, MPH at 301-827-0387.

• Studies of people with genetic disorders related to abnormal function of the creatine transporter gene and creatine transport deficiency. This observational protocol investigates the natural history of Creatine Transporter Deficiency (CTD) in males. As an addendum to a multi-site study, this research focuses on establishing baseline characteristics through extensive neurological and metabolic evaluations. Utilizing procedures such as EEG, Magnetic Resonance Spectroscopy (MRS), and lumbar puncture, the study aims to identify and validate potential biomarkers of brain metabolism to provide meaningful endpoints for future therapeutic trials. Contact Derek Alexander, MPH at 301-827-0387.

• Study of those with MEHMO (Mental disability, Epileptic seizure, Hypopituitarism/hypogenitalism, Microcephaly, Obesity) syndrome, or an eIF2-pathway related disorder, and their family members. This prospective natural history study characterizes MEHMO syndrome and other eIF2-pathway-related conditions. The research longitudinally follows affected individuals, carriers, and unaffected family members to delineate disease pathophysiology and natural progression. Through the systematic collection of clinical data and biomaterials, the study aims to identify fluid biomarkers and establish a disease severity scale to guide future therapeutic interventions. Contact An Ngoc Dang Do, M.D., PhD. at an.dangdo@nih.gov or Kisha Jenkins, RN at 301-594-2005.

• Investigations of Juvenile Neuronal Ceroid Lipofuscinosis (CLN3) and CLN3-Related Conditions. This natural history study prospectively evaluates individuals with CLN3 disease or related neuronal ceroid lipofuscinoses (NCLs) through extensive clinical assessments, imaging, and biospecimen collection. The study aims include better characterization of disease progression, discovery of biomarkers, and translation of these findings into research and clinical care. Contact An Ngoc Dang Do, M.D., PhD. at an.dangdo@nih.gov or Kisha Jenkins, RN at 301-594-2005.

• Identifying Genome Variants and Evaluating PRDM9 and piRNA Clusters as Candidates for Infertility in a Cohort of individuals with Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI). This study enrolls adults with non-obstructive azoospermia (NOA) or primary ovarian insufficiency (POI) to identify genetic causes of infertility using genome sequencing and targeted long-read sequencing of PRDM9 and piRNA clusters. The goal is to determine whether variants in these genes contribute to infertility and to improve genetic diagnosis and prognosis for affected individuals. Contact Todd S. Macfarlan, PhD. at macfarlants@mail.nih.gov.

• Children's Growth and Behavior Study. This longitudinal observational study aims to disentangle patterns of disinhibited eating in youth by identifying biopsychosocial mechanisms that increase risk for excessive weight gain and obesity-related comorbidities. The study will enroll 500 healthy boys and girls with and without obesity ages 8–17 and their parents, conducting extensive baseline experimental assessments and annual follow-up evaluations to clarify early risk factors and inform targeted interventions for pediatric obesity. Contact Bobby Cheon, PhD. at bobby.cheon@nih.gov.

Lymphatic Disorders

• Studies of patients with suspected or confirmed disorders of the lymphatic system. This prospective, multicenter natural history study characterizes lymphatic anomalies by systematically evaluating disease phenotypes and long-term outcomes. The research establishes a longitudinal cohort and biospecimen repository to define clinical features, determine best practices for genetic diagnosis, and assess malignant potential. The primary goal is to improve prognostication, establish screening guidelines, and identify novel endpoints for future clinical trials. Contact Sarah Sheppard, M.D., PhD. at sarah.sheppard@nih.gov, Andrea Bowling, DNP at Andrea.Bowling@nih.gov or the study team at NICHD_LymphaticAnoma@mail.nih.gov,.

Maternal-Fetal Medicine and Translational Imaging

• Studies of mirror neuron network (MNN) dysfunction as an early biomarker of neurodevelopmental disorder. In this study, researchers use fNIRS combined with electroencephalography (EEG) to measure brain activity in the MNN, which is associated with the development of sophisticated social behaviors that emerge in typical infants. The first part of the study is investigating whether MNN activation can be elicited in adult participants using a motor observation and a simultaneous execution paradigm of EEG/fNIRS systems. The researchers will next measure the same signals in typically developing infants and infants at risk for developmental delays when they are between 9 and 12 months of age. At-risk infants will be evaluated again at 24 months of age to detect any deviations in their social communicative development. Examining their developmental status at 24 months in relation to their initial neural data will help determine whether MNN activation can predict developmental outcomes. Contact Amir Gandjbakhche, PhD. at gandjbaa@mail.nih.gov.

• Development of a Wearable Point of Care Monitoring Device for Pediatric Obstructive Sleep Apnea. This prospective clinical study (POSA-NIRS) evaluates wearable point-of-care near-infrared spectroscopy (NIRS) devices to measure cerebral and peripheral tissue oxygen saturation in children with and without obstructive sleep apnea (OSA) during overnight polysomnography at the NIH Clinical Center. The study aims to characterize NIRS-derived hemodynamic and oxygenation changes during sleep and apnea events, correlate these measures with standard polysomnography parameters, and explore changes in tissue oxygenation before and after OSA treatment (tonsillectomy/adenoidectomy or CPAP). Contact Bruce Tromberg, PhD. at bruce.tromberg@nih.gov and Thien Nguyen, PhD. at thien.nguyen4@nih.gov.

Pediatric and Adolescent Gynecology

• Data collection study on pediatric and adolescent gynecology conditions. This study is performing deep phenotyping and data collection of children and adolescents presenting with gynecologic conditions, including congenital anomalies. Contact Veronica Gomez-Lobo, M.D. at veronica.gomez-lobo@nih.gov or Harveen Kaur at harveen.kaur@nih.gov.

• Hormone Replacement Therapy in Adolescents with Premature Ovarian insufficiency. This Phase III clinical trial evaluates transdermal 17β-estradiol and micronized progesterone as hormone replacement therapy (HRT) in adolescents with premature ovarian insufficiency (POI). The study characterizes the clinical and genetic features of adolescents with POI and examines longitudinal changes in bone mineral density, musculoskeletal, metabolic, cardiovascular outcomes, and quality-of-life over a two-year treatment period compared with healthy control participants. Contact Catherine Gordon, M.D., M.S. at catherine.gordon@nih.gov or Milena Jovanovic, PhD. at milena.jovanovic@nih.gov.

• Gonadal tissue freezing for fertility preservation in individuals at risk for ovarian dysfunction, premature ovarian insufficiency and clinically indicated gonadectomy. Children and adolescents with Turners Syndrome, galactosemia, premature ovarian/gonadal insufficiency or a condition that is associated with increased risk of gonadal tumor will undergo removal of one ovary and ovarian tissue cryopreservation/freezing to see if this procedure allows for the possibility of preserving fertility. The researchers are also obtained tissue to find out how these conditions affect the ovaries, testes, or gonads and why people with these conditions have trouble having their own genetic/biological children. The researcher are looking to see if Ovarian or Gonadal Tissue Cryopreservation(freezing) has the possibility of preserving fertility and is safe for people like you. Of note, ovarian tissue is cryopreserved and stored for the participant’s own future use. Contact Veronica Gomez-Lobo, M.D. at veronica.gomez-lobo@nih.gov or Harveen Kaur at harveen.kaur@nih.gov.

• Biorepository for those who undergo ovarian tissue freezing before gonadotoxic therapy. In this study, researchers are creating a databank of ovarian tissue obtained during ovarian tissue cryopreservation (OTC), which is performed as standard care for fertility preservation in individuals who will receive gonadotoxic therapy. The NIH will provide OTC as a clinical service and will request a portion of the tissue to use for research. Contact Veronica Gomez-Lobo, M.D. at veronica.gomez-lobo@nih.gov or Harveen Kaur at harveen.kaur@nih.gov.

• Studies on androgen receptor sensitivity and implications for health and wellbeing: A natural history study of patients with androgen insensitivity. Research on androgen-receptor genes and receptor abnormalities can improve care for those affected with this rare condition. The research may also elucidate possible androgen receptor-mediated explanations for differences in physiology and health in other populations. Contact Veronica Gomez-Lobo, M.D. at veronica.gomez-lobo@nih.gov or Harveen Kaur at harveen.kaur@nih.gov.

• Implications of maternal 45, X mosaicism as a secondary genomic finding following cell-free DNA sequencing during pregnancy. This natural history study will identify health risks among people with 45, X mosaicism discovered during pregnancy. Mosaicism is a condition in which cells within the same person have a different genetic makeup. Sometimes, a type of mosaicism called 45, X may not be discovered until a person undergoes routine tests during pregnancy. This work seeks to expand knowledge about discovery of 45, X mosaicism during pregnancy and how it may affect long-term health. Contact Veronica Gomez-Lobo, M.D. at veronica.gomez-lobo@nih.gov or Harveen Kaur at harveen.kaur@nih.gov.

Physical Biology and Medicine

• Clinical and Laboratory Study of Rare Skeletal Disorders. This is a single-site, retrospective and prospective clinical and laboratory study conducted at the NIH Clinical Center to evaluate individuals with known or suspected rare skeletal disorders, including affected participants and their unaffected family members .The study aims to define or further clarify the genetic causes of skeletal disorders and establish genotype–phenotype correlations through clinical evaluation and genetic testing, ultimately improving diagnosis, counseling, and understanding of natural history. Contact Carlos Ferreira, M.D. at carlos.ferreira@nih.gov.

• Uncovering Genes Behind Cartilage Tumors and Vascular Anomalies Using Genomic Sequencing. This natural history study will comprehensively evaluate patients with Ollier Disease and Maffucci Syndrome through detailed clinical assessments, imaging and biospecimen collection to better define disease presentation and progression, of these rare disorders. This translational study will perform genomic and molecular analyses of serum and tumor samples to identify the genetic drivers of these disorders and examine genotype-phenotype correlations. The primary intramural site is the NIH Clinical Center where patient evaluations take place, with Johns Hopkins University serving as the coordinating center. Contact Catherine Gordon, M.D., M.S. at catherine.gordon@nih.gov or Milena Jovanovic, PhD. at milena.jovanovic@nih.gov.

Epidemiology Branch

• Study of Pregnancy and Neonatal Health (SPAN). Study of Pregnancy and Neonatal Health (SPAN), Pregnancy Cohort Investigating Paternal Contributions, Placental/Fetal Genetics, and Timing of Delivery on Neonatal Health. This multi-site study will recruit a cohort of pregnant women and their male partners. SPAN integrates research approaches to understand environmental and genetic mechanisms that underpin key pathways important for health and disease. Contact Edwina Yeung, PhD. at edwina.yeung@nih.gov.