Once-daily dual-release hydrocortisone for adults with congenital adrenal hyperplasia

Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment

This will test whether a once-daily dual-release hydrocortisone controls hormones, metabolic effects, and quality of life better than conventional multiple-dose glucocorticoids in adults with 21-hydroxylase congenital adrenal hyperplasia.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Federico II University (Academic / other)
• Locations: 1 site (Naples)
• Trial ID: NCT03760835 on ClinicalTrials.gov

What this trial studies

This open, controlled Phase 4 study compares a dual-release hydrocortisone formulation (Plenadren) given once daily with conventional immediate-release glucocorticoid regimens in adults with 21-hydroxylase congenital adrenal hyperplasia. Participants are switched or randomized from their usual therapy and followed for clinical, anthropometric, metabolic, hormonal, bone, reproductive/sexual, psychological, and quality-of-life outcomes as well as treatment compliance. The rationale is that the dual-release formulation better mimics the normal circadian cortisol rhythm and may reduce the adverse metabolic and quality-of-life effects seen with non-physiological dosing. Safety, tolerability, and effects on androgen control are key measured endpoints.

Who should consider this trial

Good fit: Adults aged over 18 with a confirmed diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency who are on stable conventional glucocorticoid therapy and willing to change their regimen are ideal candidates.

Not a fit: Patients with severe organ dysfunction, active substance abuse, significant psychiatric illness, night shift workers, those needing chronic glucocorticoids for other diseases, on interacting enzyme-inducing drugs, or with known hypersensitivity to the dual-release product are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, once-daily dual-release hydrocortisone could improve hormone control, lower metabolic risk, reduce side effects, and simplify dosing to improve adherence and quality of life.

How similar studies have performed: Dual-release hydrocortisone has shown benefits in other forms of adrenal insufficiency by better mimicking circadian cortisol, but data specifically in adult CAH are limited and this approach remains relatively novel for this condition.

Eligibility criteria

Inclusion Criteria:

* males and females aged \>18 years;
* established diagnosis of adrenal insufficiency in congenital adrenal hyperplasia due to 21-hydroxylase deficiency;
* stably treated with conventional glucocorticoids, available to change their regimen according to random allocation
* written informed consent/assent to participate in the study in compliance with local regulations.

Exclusion Criteria:

* clinical or laboratory signs of severe cerebral, respiratory, hepatobiliary or pancreatic diseases, renal dysfunction, gastrointestinal emptying, or motility disturbances (i.e. chronic diarrhea), significant psychiatric illnesses;
* history of/or current alcohol and/or drug abuse;
* night shift workers;
* underlying diseases that could necessitate treatment with glucocorticoids;
* therapies with hepatic enzyme induction drugs interfering with glucocorticoid kinetics, or immunosuppressive steroid therapy;
* patients with a documented intolerance/known hypersensitivity to dual release hydrocortisone;
* vulnerable populations, such as elderly, cancer patients, pregnant and lactating women;
* history of non-compliance to medical regimens, or potentially unreliable patients

Where this trial is running

Naples

• Federico II University — Naples, Italy (Recruiting)

Study contacts

• Study coordinator: Rosario Pivonello, M.D., PhD, Professor

Conditions Congenital Adrenal Hyperplasia; congenital adrenal hyperplasia; glucocorticoid treatment; dual release hydrocortisone