Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Gland and Hormone Related Diseases

Neoplasms

Syndrome

Infertility

Azoospermia

Klinefelter Syndrome

Testicular Neoplasms

Hypogonadism

Oligospermia

Gonadal Disorders

Endocrine System Diseases

Infertility, Male

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Male Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

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Methyltestosterone

Androgens

Testosterone

Testosterone undecanoate

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Testosterone 17 beta-cypionate

Castor Oil

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Antineoplastic Agents, Hormonal

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Castor

Testosterone undecanoate 1000mg injection at baseline (0-week), 6-week, 18-week, 30-week

Injection 4 ml of castor oil at baseline (week-0), week-6, week-18, week-30

Testosterone undecanoate 1000mg (in 4 ml of castor oil injections) at baseline (0-week), 6-week, 18-week, 30-week

4 ml of Castor Oil injected at baseline (0-week), 6-week, 18-week, 30-week.

Andrea Lenzi, MD

Andrea Isidori, MD, PhD

Vincenzo Bonifacio, MD, PhD

Patients with infertility often presents alterations at ultrasonographic examination of the testis. These alterations include a much higher incidence of small, multiple, non-palpable hypoechoic micro-nodules that can show internal vascularization. This finding often create alarm and anxiety, because it has to be placed in a differential diagnosis versus low-stage malignant germ cell tumors. Nevertheless, explorative surgery reveal that a consistent number of these lesion are benign, due to Leydig cell hyperplasia or Leydig cell tumours. The purpose of this study is to evaluate the effects of androgen therapy on the size and number of non-palpable hypoechoic micro-nodules in patients with elevated gonadotropin levels.

Patients with the testicular dysgenesis syndrome, that comprises a variable spectrum of clinical manifestations, such as infertility, cryptorchidism, hypospadias, impaired spermatogenesis and testicular germ cell neoplasms, often develop alterations in the Leydig cell compartment. These alterations range from abnormal localization and clustering to hyperplasia or tumorous formation.

Leydig cell tumors (LCTs), although uncommon in the general population, are the most frequent non-germ cell testicular neoplasms, and their incidence has been reported increasingly growing, especially in infertile patients. Given that the focal areas of Leydig cell hyperplasia are nowadays easily detectable at ultrasonography of the testis (US), as small non-palpable hypoechoic micro-nodules that can show internal vascularization, their finding create a diagnostic challenge versus low-stage malignant germ cell tumors.

Patients with testicular dysgenesis syndrome in general exhibit an elevation of Follicle-Stimulating Hormone (FSH), but in these patients, very frequently, even Luteinizing Hormone (LH) is above the reference range. The latter can work as a growth factor for Leydig cells. Since exogenous testosterone can suppress LH levels, it could be that androgen therapy could revert the LH-induced growth stimulation of Leydig cell compartment.

The purpose of this study is to evaluate the effects of androgen therapy on the size and number of non-palpable hypoechoic micro-nodules in patients with elevated gonadotropin levels.

The purpose of this study is also to evaluate whether the behavior (UltraSonographic appearance, US) of the non-palpable hypoechoic micro-nodules during a 4-month trial of testosterone therapy can offer a novel diagnostic tool in the differential diagnosis of benign versus malignant testicular nodules.

The trial will be open only for patients with multiple non-palpable hypoechoic micro-nodules that have an elevation of both FSH and LH and that are not seeking conception.

Participants in the study will be randomized to one of two treatment groups, receiving either testosterone undecanoate (low-dose androgen) or placebo, for two 6 months. All participants will be evaluated for safety at the beginning of the study and at 2, 4, and 6 months with careful history, physical examination, blood sampling and testicular ultrasonography. Patients will also be offered the possibility to perform Magnetic Resonance Imaging (MRI) of the testis at baseline and after treatment, and/or surgical enucleation of the lesions.

Androgen for Leydig Cell Proliferation

Androgen Treatment in Leydig Cell Proliferation

Percentage change of the area of the lesions multiplied by the number of the measured lesions: \[(area_1 + area_2 + area_3 + ... + area_n)\*n\].

The latter measure account for reduction in the number of lesions (disappearance).

Percentage change in the area of the lesion (measured with computer assisted graphics).

Reduction of the serum Luteinizing Hormone (LH) levels during testosterone therapy

Evaluation of sperm cell production after testosterone withdrawal.

Changes in the number of areas / nodules / lesions in the long-term safety assessment

University of Roma La Sapienza

Professor of Endocrinology

Nervous System Diseases

Musculoskeletal Diseases

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Behaviors and Mental Disorders

Heart and Blood Diseases

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Skin and Connective Tissue Diseases

Rare Diseases

Sclerosis

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Hypoparathyroidism

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Chronobiology Disorders

Muscular Dystrophy

Becker Muscular Dystrophy

Duchenne Muscular Dystrophy

Tuberous Sclerosis Complex

22q13.3 Deletion Syndrome

22q11.2 Deletion Syndrome

Lymphatic Malformations

Psychoeducation around the diagnosed disorder, early development, and service navigation along with parent-child interaction activities, parent coaching, and family/parent well-being support.

Parent-Infant Inter(X)action Intervention (PIXI)

Anne Wheeler, PhD

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.

The primary goal of the proposed project is to develop and test, through an iterative process, an intervention to address and support the development of infants with a rare neurogenetic condition (e.g., fragile X, Angelman, Prader-Willi, Dup15q, Phelan-McDermid, Rhett, Smith Magenis, Williams, Turner, Kleinfelter, Down syndromes, Duchenne muscular dystrophy) identified prior to emergence of symptoms. PiXI aims to utilize the foundational knowledge available around the development of and early intervention for at-risk infants to both understand the needs of and provide intervention services for families of infants diagnosed pre-symptomatically with rare neurogenetic disorders.

The investigators aim to 1) develop PIXI with a pilot sample of families, 2) test the preliminary effects of PIXI on infant and parent outcomes

The intervention, called Parent-infant Interaction Intervention (PIXI) is a comprehensive intervention provided across the first year of life for parents/caregivers of infants identified with a rare neurogenetic disorder. It includes psychoeducation around the disorder, early development, and service navigation along with parent-child interaction activities, parent coaching, and family/parent well-being support.

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

Piloting an Early Intervention Program for Infants With Rare Neurogenetic Disorders

A social validity measure will be completed to better understand to inquire about family satisfaction with aspects of the intervention including curriculum, timing, goals targeted, and perceived effects of the intervention.

A social validity measure will be completed to better understand to inquire about family satisfaction with aspects of the intervention including curriculum, timing, goals targeted, and perceived effects of the intervention. Qualitative interviewing will be also be conducted to examine parent perceptions of feasibility and acceptability.

Overall intervention fidelity will be measured by determining if the following goals were achieved:

Enrollment target of 10-15 families 80% retention rate with at least 75% completing the 20 sessions across Phase 1 and Phase 2

Internal parent implementation and engagement forms will be used to measure parent participation across both intervention phases. These components include parent readiness for the session, attention to materials, participation in topic discussion, appropriateness of intervention activity practice, and general presentation with their child.

Descriptive statistics around early learning, motor, communication skills, interpersonal, and adaptive skills in the sample will be derived from the Vineland Adaptive Behavior Scales, Third Edition: Parent/Caregiver Report (Vineland-3). Subdomain v-Scaled scores range from 1-24 with higher numbers indicating greater performance; while domain scores are presented in standard score formats with a range of 20-140 with higher scores indicating greater performance.

A combination of measures will be used across study engagement to assess parent reported autism symptomology. These measures include the Communication and Symbolic Behavior Scale (CSBS). The parent report developmental profile is a standardized measure is completed to evaluate language and social communication predictors. A total of 57 points are available with age corresponding cutoff scores for clinical concern.

A combination of measures will be used across study engagement to assess parent reported autism symptomology. These measures include the Modified Checklist for Autism in Toddlers (MCHAT). The Modified Checklist for Autism in Toddlers is a scientifically validated tool for screening children between 16 and 30 months of age that assesses risk for autism spectrum disorder (ASD).Scores range from 0-20 with corresponding ranges for cutoff scores warranting further follow-up.

A combination of measures will be used across study engagement to assess parent reported autism symptomology. These measures include the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). The ADOS-2 is a semi-structured, standardized assessment of communication, social interaction, play, and restricted and repetitive behaviors. It is directly administered to the participant and behaviors are scored. Total scores range based on age of participant/module administered. Scores are calculated and compared against cutoff scores for autism spectrum and autism.

A combination of measures will be used across study engagement to assess parent reported autism symptomology. These measures include the TELE-ASD-PEDS. The TELE-ASD-PEDS was developed by researchers at Vanderbilt University to assess remotely autism symptomology. The TELE-ASD-PEDS measures communication, social interaction, play, and restricted and repetitive behaviors. It is administered via telehealth and behaviors are scored. Total scores range based on age of participant/module administered. Scores are calculated and compared against cutoff scores for autism spectrum and autism.

A combination of measures will be used across study engagement to assess parent reported autism symptomology. These measures include the Repetitive Behavior Scales (RBS). The RBS-EC is a questionnaire measure of restricted and repetitive behaviors designed for use in children from infancy through early school age. It is intended to capture individual differences across a broad range of behaviors associated with the repetitive behavior domain. Total scores range from 0-136 with a higher score indicating greater need/presence of behaviors.

University of North Carolina, Chapel Hill

RTI International

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Androgen for Leydig Cell Proliferation	NCT01206270	Klinefelter Syn... Hypergonadotrop... Hypergonadotrop... Hypergonadotrop...	Testosterone un... Castor Oil	18 Years - 60 Years	University of Roma La Sapienza
Androgen for Leydig Cell Proliferation	NCT01206270	Klinefelter Syn... Hypergonadotrop... Hypergonadotrop... Hypergonadotrop...	Testosterone un... Castor Oil	18 Years - 60 Years	University of Roma La Sapienza
Parent and Infant Inter(X)Action Intervention (PIXI)	NCT03836300	Fragile X Syndr... Angelman Syndro... Prader-Willi Sy... Dup15Q Syndrome Duchenne Muscul... Phelan-McDermid... Rett Syndrome Smith Magenis S... Williams Syndro... Turner Syndrome Klinefelter Syn... Chromosome 22q1... Tuberous Sclero... Down Syndrome	Parent-Infant I...	- 99 Years	RTI International

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