ClinicalTrials.gov record NCT07622030
Hydrocortisone Modified-release in Adults: Real-world Monitoring of Longitudinal Outcomes in coNgenital Adrenal hYperplasia
Long-term Real-world Outcomes of Chronotherapy With Modified-release Hydrocortisone in Congenital Adrenal Hyperplasia
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This is an ongoing longitudinal observational study collecting past and routine clinical data on adults with genetically confirmed 21-hydroxylase deficiency CAH who switched from conventional glucocorticoid therapy to modified‑release hydrocortisone (MR‑HC). The study uses existing medical records and prospective follow-up visits (planned at ~2, 4, 6, 12 months after switch and yearly thereafter) to track biochemical, metabolic, cardiovascular, reproductive, and bone outcomes. All data come from routine care and the study reports real-world outcomes over a target duration of about 5 years.
What it is studying. The study is gathering real-world, long-term information on clinical and laboratory outcomes after switching adults with 21-hydroxylase deficiency CAH from conventional glucocorticoids to modified‑release hydrocortisone (MR‑HC).
What the researchers hope to learn. To describe long-term real-world outcomes of chronotherapy with modified‑release hydrocortisone in adults with genetically confirmed 21-hydroxylase deficiency CAH, including biochemical control (morning 17‑hydroxyprogesterone, androstenedione, ACTH, cortisol), mineralocorticoid measures, frequency of adrenal crises, glucocorticoid dosing, metabolic and cardiovascular measures, reproductive outcomes, bone health (DXA and bone markers), and quality-of-life scores.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
Classic congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder caused by a defect in the enzyme cascade regulating adrenal steroidogenesis; in approximately 95% of cases the defect is located in CYP21A2, the gene encoding 21-hydroxylase, and is characterized by defective adrenal steroidogenesis and cortisol deficiency. Due to the loss of physiological cortisol feedback on the hypothalamus and pituitary corticotropic cells, ACTH secretion is increased. This results in the accumulation of 17-hydroxyprogesterone (17OHP) proximal to the enzymatic defect in steroidogenesis, which in turn stimulates overproduction of the adrenal androgen precursor androstenedione and adrenal hyperplasia. Treatment of CAH is tailored to the patient and disease severity, aiming to replace cortisol and aldosterone deficiencies while controlling androgen excess and avoiding glucocorticoid overtreatment. Immediate-release hydrocortisone administered multiple times daily remains the recommended first-line treatment in growing children, whereas adult patients are frequently treated with hydrocortisone, prednisone, prednisolone or dexamethasone. However, conventional glucocorticoid regimens cannot adequately reproduce the physiological circadian rhythm of cortisol secretion. In physiological conditions, ACTH-driven cortisol secretion follows a clear circadian rhythm characterized by low evening levels, nocturnal increase between 2:00 and 4:00 a.m., a morning peak upon awakening, and progressive decline during daytime. Dual daytime dosing of immediate-release hydrocortisone in CAH can control ACTH-driven adrenal androgen secretion during the day; however, because of its rapid absorption into the bloodstream and short half-life, the evening dose of hydrocortisone cannot adequately suppress the nocturnal ACTH surge and ACTH-driven adrenal androgen overproduction. Consequently, patients are often exposed to supraphysiological glucocorticoid doses during nighttime hours in an attempt to control morning hyperandrogenism. The disruption of physiological cortisol homeostasis contributes to poor cardiometabolic profile, obesity, insulin resistance, impaired fertility, reduced quality of life, and increased cardiovascular morbidity and mortality observed in patients with CAH. Bone health may also be impaired in patients with CAH because of chronic glucocorticoid exposure and androgen imbalance. Previous studies demonstrated reduced lumbar and femoral bone mineral density and increased fracture risk in both male and female patients. Modified-release hydrocortisone (MR-HC; Efmody®) is a multiparticulate formulation developed to better reproduce physiological cortisol circadian rhythm through chronotherapy. Previous phase II and phase III studies demonstrated improved biochemical control, reduction in androgen excess, lower glucocorticoid exposure, improved fertility outcomes, and sustained long-term efficacy compared with conventional glucocorticoid regimens. However, real-world longitudinal data regarding long-term biochemical, metabolic, cardiovascular, reproductive and skeletal outcomes remain limited, particularly in adult patients transitioning from pediatric to adult endocrine care. The present study is a single-center, retrospective and prospective, longitudinal, open-label observational cohort study aimed at evaluating the long-term real-world outcomes of chronotherapy with modified-release hydrocortisone in adult patients with genetically confirmed 21-hydroxylase deficiency CAH. Retrospective clinical, biochemical and radiological data already available from routine clinical care will be collected from medical records, while prospective observational follow-up will continue according to routine endocrine clinical practice.
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Age ≥18 years;
- Genetically confirmed diagnosis of 21-hydroxylase deficiency congenital adrenal hyperplasia;
- Transition from conventional glucocorticoid therapy to modified-release hydrocortisone according to routine clinical practice;
- Stable glucocorticoid and mineralocorticoid therapy before transition;
- Ability to understand study procedures and provide informed consent for prospective data collection whenever applicable
Exclusion criteria
- Age <18 years;
- Pregnancy or breastfeeding;
- Severe uncontrolled medical or psychiatric illness;
- Use of glucocorticoids for indications other than CAH;
- Use of drugs interfering with glucocorticoid metabolism;
- History of bilateral adrenalectomy
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
The study is designed as an ongoing longitudinal observational cohort intended to evaluate short-term and long-term outcomes of MR-HC treatment in a real-world setting. At the time of protocol drafting, retrospective and prospective data are available for approximately 32 patients, with follow-up extending up to 24-36 months in some cases. Additional eligible patients may be included prospectively during the observational phase of the study. Follow-up assessments are planned at approximately 2, 4, 6, and 12 months after treatment transition and yearly thereafter whenever available as part of routine clinical practice. Interim analyses may be performed on available datasets before completion of long-term follow-up in order to evaluate clinically relevant outcomes emerging from real-world experience. All procedures and laboratory assessments included in the study are part of routine clinical management of patients with CAH and do not imply additional costs for patients or for the institution.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
The study uses review of past medical records plus prospective follow-up during routine endocrine clinic visits over a target duration of about 5 years. Data collected at clinic visits include blood tests (hormones and metabolic labs), midnight salivary cortisol, measurements such as weight, waist and blood pressure, bone density scans (DXA) when done, and quality‑of‑life questionnaires (SF‑36 and AddiQoL). The study will also record events such as adrenal crises and any changes in glucocorticoid dosing. All procedures are described as part of routine clinical care and the record states they do not imply additional costs for patients or the institution.
How the study is structured. An observational cohort combining retrospective review of existing clinic records with prospective routine follow-up visits. Participants' clinical data and test results collected during usual care are compared over time after transition to MR‑HC; follow-up assessments are planned early after transition (2–12 months) and yearly when available.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- No sites are listed on the registry yet. Where will the study take place?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on congenital adrenal hyperplasia
Important dates
- Study start
- Jul 31, 2026 (estimated)
- Primary completion
- Aug 31, 2026 (estimated)
- Study completion
- Jul 31, 2031 (estimated)
- Target enrollment
- 100 participants (estimated)
- Last updated on registry
- Jun 8, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- IRCCS San Raffaele
- Principal investigator
- Prof. Paola Loli, Principal Investigator
IRCCS San Raffaele
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Paola Loli, MD 📞 +39 02 2643 ext. 8959 ✉ loli.paola@hsr.it
- Umberto Terenzi, MD 📞 +39 02 2643 ext. 8959 ✉ trials.endocrinologia@hsr.it
Participating sites
Study locations have not been posted on ClinicalTrials.gov yet. This study is not yet recruiting, so sites may be added when recruitment begins. The central study contact above may be able to tell you about planned sites.
Terms used on this page · explanations by MedicalUpdates.ai
- glucocorticoid
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- half-life
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- phase II
- A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
- phase III
- A later-stage study, usually with more participants, designed to give stronger evidence about how well a treatment works and how safe it is. It often compares the treatment with standard care or a placebo, and results may support an application for approval.
- open-label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- long-term follow-up
- Observation that continues for years after the study treatment, often required for gene and cell therapies.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials