About this trial

This is a multicenter study designed to assess the effects of groundbreaking CAH therapies on a spectrum of clinical and biochemical outcomes, with a special emphasis on reproductive and sexual health. Fertility is a profound concern for individuals with CAH, given the high prevalence of gonadal dysfunction that arises from the hormonal derangements that characterize this complex disease. At our endo-ERN accredited center for rare diseases at Policlinico Umberto I, addressing these fertility issues in CAH patients represents a daily commitment. The revolution of the pharmacological management of CAH is one of the most debated topics to date. Data on the effects of novel management options for CAH on fertility are scarce, but the anecdotal improvements in sperm count and menstrual regularity reported in the latest clinical trials have significantly motivated us to design the CALLIOPE study. Thus, we aim to delve deeper into the fertility and sexual function of CAH patients, employing advanced seminal parameter evaluations, multiparametric gonadal ultrasound, and sophisticated hormonal analyses in both females and males performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Beyond fertility, the CALLIOPE trial aspires to provide further understanding of therapy's effects on body composition, metabolism, immune function, coagulation, and quality of life, among other factors. We will explore the immunological impact of novel CAH therapies by quantifying Peripheral Blood Mononuclear Cells (PBMCs) and analyzing transcriptomic profiles to unveil gene expression patterns and identify biomarkers that could signal therapeutic targets or disease management strategies in CAH. Moreover, seminal plasma will be used to assess the expression of adrenal miRNAs regulating steroidogenesis and metabolism.

The research will be conducted at our rare disease referral center (Policlinico Umberto I, Sapienza University of Rome) in collaboration with leading centers across Italy: Modena (Università degli Studi di Modena e Reggio Emilia), Naples (Università Federico II), Rome (Ospedale Sant'Andrea) and Bologna (Alma Mater Studiorum - Università di Bologna).

https://isidorilab.com/home

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult patients, males in the age range 18-65 years and pre-menopausal females in the age range 18-55 years;

a known/new diagnosis of CAH.

Disqualifiers

BMI > 40 Kg/m2;

Any other concomitant condition requiring steroid treatment;

Severe liver and/or kidney disease;

Thyroid dysfunctions (overt hyperthyroidism and hypothyroidism);

Trial population

Subjects with congenital adrenal hyperplasia (CAH) under glucocorticoid treatment

Trial design

Design model

Case-only

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

50 Participants

are grouped into 1 trial group

Group A: Patients with Congenital Adrenal Hyperplasia (CAH)

Trial outcomes

Primary outcomes

1

Change in sperm concentration (total count per ejaculate) at semen analysis (male subjects)

Sperm concentration will be evaluated through standard semen analysis in male participants, according to WHO guidelines. Measurements will be used to assess changes over time in relation to disease control and treatment modifications. Semen analyses will be repeated at follow-up visits if clinically indicated or in case of significant therapeutic changes. Unit of Measure: millions per ejaculate (10⁶/ejaculate)

Time frame

At baseline and during follow-up (up to 5 years)

2

Change in sperm concentration (concentration per mL) at semen analysis (male subjects)

Sperm concentration will be evaluated through standard semen analysis in male participants, according to WHO guidelines. Measurements will be used to assess changes over time in relation to disease control and treatment modifications. Semen analyses will be repeated at follow-up visits if clinically indicated or in case of significant therapeutic changes. Unit of Measure: millions per mL (10⁶/mL)

Time frame

At baseline and during follow-up (up to 5 years)

3

Change in Serum Testosterone:LH ratio (female subjects)

Assessment of changes in the ratio between serum total testosterone and luteinizing hormone (LH) concentrations in female participants. Blood samples will be collected in the early follicular phase or as appropriate based on menstrual status. The ratio will be calculated at each time point, and changes will be expressed as percent change from baseline or through paired comparison. The aim is to evaluate this ratio as a potential biomarker of hyperandrogenism severity and treatment response. Unit of Measure: Ratio (ng/dL per IU/L)

Time frame

At baseline and during follow-up (up to 5 years)

4

Change in serum Estradiol:FSH ratio (female subjects)

Evaluation of changes in the ratio between serum estradiol (E2) and follicle-stimulating hormone (FSH) concentrations in female participants. Blood samples will be collected in the early follicular phase when possible or based on clinical context. The E2:FSH ratio will be calculated at each visit and used to assess hypothalamic-pituitary-ovarian axis function and treatment effects over time. Changes will be analyzed using paired comparisons or percentage variation from baseline. This outcome is part of a broader hormonal assessment that includes additional ratios such as Testosterone:LH. Unit of Measure: Ratio (pg/mL per mIU/mL)

Time frame

At baseline and during follow-up (up to 5 years)

Secondary outcomes

1

Number of pregnancies and childbirths from baseline

For female participants and for partners of male participants who express the intention to conceive, data on the occurrence of pregnancies and childbirths will be collected during the study period. Outcomes will be reported as absolute numbers of confirmed pregnancies and live births. This measure aims to assess reproductive outcomes in patients with CAH under different treatment regimens. Unit of Measure: Count (number of pregnancies and number of childbirths)

Time frame

From baseline until the end of the study (up to 5 years)

2

Change in bilateral testicular volume and TARTs volume (scrotal ultrasound, male subjects)

Evaluation of bilateral testicular volume and testicular adrenal rest tumor (TART) volume in male participants, assessed via standardized scrotal ultrasound. Volumes will be calculated using the ellipsoid formula: Volume = width × depth × length × 0.52 Measurements will be recorded at each visit to monitor anatomical changes over time and assess the response to clinical management. Unit of Measure: volume (mL)

Time frame

At baseline and during follow-up (up to 5 years)

3

Change in fructose levels in seminal plasma (male subjects)

Biochemical evaluation of seminal plasma in male participants, specifically measuring fructose concentration. This marker reflects the function of seminal vesicles and prostate, and may provide indirect information on androgen status and reproductive function. Unit of Measure: mg/dL

Time frame

At baseline and during follow-up (up to 5 years)

4

Change in Circadian, multi-matrix, serum, urinary and salivary LC-MS/MS steroid profiles

* From blood samples taken at 8 AM, 12 AM, 4 PM and 8 PM, several steroids including glucocorticoids, mineralocorticoids, androgens, and their precursors and metabolites will be evaluated; * 24-hours urine samples will be used to evaluate several steroids and their metabolites and to estimate enzyme activities (11β-Hydroxysteroid dehydrogenase type 1/2, 5α-reductase) * All patients will collect at their home saliva samples at 8 AM, 10 AM, 12 PM, 4 PM, 6 PM, 8 PM and 12 AM. Saliva samples will be used to assess steroid metabolism. Unit of measure: ng/mL for all steroids

Time frame

At baseline and during follow-up (up to 5 years)

Other outcomes

1

Availability of biological samples for future biomarker analyses

Description: Plasma, serum, and urine samples will be biobanked for future exploratory analyses, including gene expression, cytokines, miRNAs, hormones, and other circulating factors. These analyses will be exploratory. Unit of Measure: Not applicable (biological samples only)

Time frame

Samples collected at baseline and follow-up; stored until the end of the study (5 years)

Fertility And Sexual Function In CAH: CALLIOPE

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial population

Trial design

Treatments tested in this trial

Trial groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts