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Congenital Adrenal Hyperplasia Once Daily Hydrocortisone Treatment (CareOnTIME)

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ClinicalTrials.gov Identifier: NCT03760835
Recruitment Status : Recruiting
First Posted : November 30, 2018
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
Prof. Rosario Pivonello, Federico II University

Brief Summary:
This is a controlled, open study designed to compare the effects of dual-release hydrocortisone preparations versus conventional glucocorticoid therapy on clinical, anthropometric parameters, metabolic syndrome, hormonal profile, bone status, quality of life, reproductive, sexual and psychological functions and treatment compliance in patients affected by congenital adrenal hyperplasia due to 21 OH deficiency.

Condition or disease Intervention/treatment Phase
Congenital Adrenal Hyperplasia Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) Drug: Dual release hydrocortisone (plenadren) Phase 4

Detailed Description:

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder characterized by cortisol and in some cases aldosterone deficiency, associated with androgen excess. Treatment goals are to replace cortisol deficiency, to control androgen levels, while avoiding the adverse effects of exogenous glucocorticoids. A variety of glucocorticoid treatments have been used in an attempt to control the overnight increase in adrenal androgens. However, there is no consensus on the optimum management of congenital adrenal hyperplasia adults. Current evidence in patients with adrenal insufficiency suggests that the inability of current regimens to replace physiological circadian cortisol levels, leads to adverse clinical outcomes, including metabolic syndrome, insulin resistance, increased risk factors for cardiovascular diseases, bone and immune alterations, sleep disturbances and quality of life impairment. Moreover, the risk for poor treatment compliance, in case of multiple daily doses treatment regimens, should not be excluded. In this trial a dual-release hydrocortisone preparation, that been able to mimic the circadian pattern of circulating cortisol, was studied in patients with adrenal insufficiency due to congenital adrenal hyperplasia.

All patients with a diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, irrespective of glucocorticoid treatment, are eligible for the inclusion in the study and may be asked to participate in the study. Patients are followed during the course of routine clinical practice for the duration of time that the study is active.

ARM1: Conventional glucocorticoid therapy is continued as before entering the study

ARM2: Dual release hydrocortisone oral tablets is administered once-daily in the fasting state. The dose is kept the same as patients had before entering the trial.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment
Actual Study Start Date : August 11, 2016
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Dual-release hydrocortisone Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone)
Treatment of congenital adrenal hyperplasia

Drug: Dual release hydrocortisone (plenadren)
Treatment of congenital adrenal hyperplasia

Active Comparator: Conventional glucocorticoids Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone)
Treatment of congenital adrenal hyperplasia




Primary Outcome Measures :
  1. Change from baseline in measurement of total and LDL cholesterol (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Single outcome measurement of cholesterol levels (mg/dl)


Secondary Outcome Measures :
  1. Change from baseline in measurement of glycaemia (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of glycaemia (mg/dl)

  2. Change from baseline in measurement of BMI (Kg/m2) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of BMI (Kg/m2)

  3. Change from baseline in measurement of blood pressure (mmHg) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of blood pressure (mmHg)

  4. Change from baseline in measurement of insulinemia (μU/mL) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of insulinemia (μU/mL)

  5. Change from baseline in measurement of triglycerides (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of triglycerides (mg/dl)

  6. Change from baseline in measurement of HDL-cholesterol (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of HDL-cholesterol (mg/dl)

  7. Change from baseline in measurement of Glycated Haemoglobin (%) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of Glycated Haemoglobin (%)

  8. Changes in bone mineral density [ Time Frame: 0, + 12 months, +24 months ]
    Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)]

  9. Changes in quality of life [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Quality of life will be measured by Addison Quality of Life (AddiQol) questionnaire, used to assess quality of life in patients suffering from adrenal insufficiency. Each question has a score ranging from 1 to 4. Total score (minimum: 30; maximum: 120) is obtained summing each question score. The higher the scores are, the better the quality of life is. No clear cut-offs are defined.

  10. Changes in sex function in males [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Sex function will be measured by International Index of Erectile Function (IIEF) questionnaire. IIEF is divided into five function domains: Erectile function (Q1-5, Q15; score range Q1-5: 0-5; score range Q15: 1-5), Orgasmic function (Q9-10; score range Q9: 0-5; score range Q10: 1-5), Sexual desire (Q11-12; score range: 1-5), Intercourse satisfaction (Q6-8; score range: 0-5), Overall satisfaction (Q13-14; score range: 1-5). The higher the domain scores are, the better the male sexual functions are.

  11. Changes in sex function in females [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Sex function will be measured by Female Sexual Function Index (FSFI) questionnaire. FSFI is divided into six domains: Desire (Q1-2; score range: 1-5), Arousal (Q3-6; score range: 0-5), Lubrification (Q7-10; score range: 0-5), Orgasm (Q11-13; score range: 0-5), Satisfaction (Q14-16; score range Q14: 0-5; score range Q15-16: 1-5), Pain (Q17-19; score range: 0-5). To obtain the full scale score (ranging from 2 to 36), each domain score range should be corrected by an individual factor (Desire: 0.6; Arousal and Lubrification: 0.3; Orgasm, Satisfaction and Pain: 0.4). The higher the score is, the better the female sexual function is.

  12. Changes in depression status [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Depression status will be measured by Beck Depression Inventory Test (BDI-II) questionnaire. Each question has a score ranging from 0 to 3. Total score (minimum: 0; maximum: 63) is obtained summing each question score. Scores range from minimum (0-13), mild (14-19), moderate (20-28), severe (29-63)

  13. Changes in treatment compliance [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Treatment compliance will be measured by Morisky Medical Adherence Scale-8 questionnaire. Each question has a score ranging from 0 to 1. Total score (minimum: 0; maximum: 8) is obtained summing each question score. Scores range from high adherence (0), medium adherence (1-2) and low adherence (>2).

  14. Incidence of Treatment Adverse Events (safety analysis) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.0 (not a scale)

  15. Changes in androgens levels [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of androstenedione/testosterone ratio

  16. Changes in sperm concentration [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Evaluation of sperm concentration according to WHO criteria

  17. Changes in ovarian follicles reserve [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Evaluation of number of ovarian follicles by conventional ultrasound imaging



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03760835


Contacts
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Contact: Rosario Pivonello, M.D., PhD, Professor +390817464983 rosario.pivonello@unina.it

Locations
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Italy
Federico II University Recruiting
Naples, Italy, 80131
Contact: Rosario Pivonello, MD,PhD,Professor    +390817464983    rosario.pivonello@unina.it   
Principal Investigator: Rosario Pivonello, MD, PhD, Professor         
Sub-Investigator: Chiara Simeoli, MD         
Sub-Investigator: Maria Cristina De Martino, MD, PhD         
Sub-Investigator: Rosario Ferrigno, MD         
Sponsors and Collaborators
Federico II University

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Responsible Party: Prof. Rosario Pivonello, Associate Professor, Federico II University
ClinicalTrials.gov Identifier: NCT03760835     History of Changes
Other Study ID Numbers: 140/16
First Posted: November 30, 2018    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Prof. Rosario Pivonello, Federico II University:
congenital adrenal hyperplasia
glucocorticoid treatment
dual release hydrocortisone

Additional relevant MeSH terms:
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Hyperplasia
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Adrenocortical Hyperfunction
Pathologic Processes
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Gonadal Disorders
Dexamethasone
Prednisone
Prednisolone
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Cortisone
Glucocorticoids
Epinephrine
Racepinephrine
Epinephryl borate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents