Fertility And Sexual Function In CAH: CALLIOPE

NCT07099456 | Recruiting

• 1 other identifier: CALLIOPE
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Congenital Adrenal Hyperplasia (CAH)

Keywords

congenital adrenal hyperplasia; CAH; fertility; LC-MS/MS; semen analysis; reproductive function

Outcome Measures

Primary Outcomes (4)

• 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)

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

• 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)

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

• 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)

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

• 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)

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

Secondary Outcomes (74)

• Number of pregnancies and childbirths from baseline

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

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

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

• Change in fructose levels in seminal plasma (male subjects)

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

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

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

• Change in Circadian quantification of Peripheral Blood Mononuclear Cells (PBMCs) subpopulations by flow cytometry

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

Other Outcomes (1)

• Availability of biological samples for future biomarker analyses

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

Study Arms (1)

Patients with Congenital Adrenal Hyperplasia (CAH)

Adult patients with a known/new diagnosis of CAH requiring chronic glucocorticoid replacement therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects with congenital adrenal hyperplasia (CAH) under glucocorticoid treatment

You may qualify if:

• 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.

You may not qualify if:

• BMI \> 40 Kg/m2;
• Any other concomitant condition requiring steroid treatment;
• Severe liver and/or kidney disease;
• Thyroid dysfunctions (overt hyperthyroidism and hypothyroidism);
• Malignant neoplasms;
• Drug and alcohol abuse;
• Use of drugs acting on hormonal levels (e.g. antiandrogens);
• Psychiatric diseases;
• Postmenopausal women;
• Women taking combined oral contraceptive pill (women) or other contraceptives will require stability for at least 6 months.

Sponsors & Collaborators

• University of Roma La Sapienza: lead
• University of Modena and Reggio Emilia: collaborator
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• Federico II University: collaborator
• S. Andrea Hospital: collaborator

Study Sites (1)

Department of Experimental Medicine, Sapienza University of Rome

Rome, Italy, 00161, Italy

RECRUITING

Related Publications (17)

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, saliva, urine and semen.

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital

Condition Hierarchy (Ancestors)

Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders

Central Study Contacts

Andrea M Isidori, MD, PhD, FRCP

CONTACT

+39 0649970540; andrea.isidori@uniroma1.it

Davide Ferrari, MD

CONTACT

+39 3403843502; davide.ferrari@uniroma1.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Endocrinology and Metabolism

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: August 1, 2025
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2030
• Last Updated: August 1, 2025

Record last verified: 2025-07

Locations

IT (1)