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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

Tracking Information
First Submitted Date  ICMJE November 9, 2018
First Posted Date  ICMJE November 30, 2018
Last Update Posted Date December 10, 2018
Actual Study Start Date  ICMJE August 11, 2016
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: November 29, 2018)
Change from baseline in measurement of total cholesterol (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
Single outcome measurement of total cholesterol (mg/dl)
Change History Complete list of historical versions of study NCT03760835 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
  • Change from baseline in measurement of glycaemia (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of glycaemia (mg/dl)
  • Change from baseline in measurement of BMI (Kg/m2) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of BMI (Kg/m2)
  • Change from baseline in measurement of blood pressure (mmHg) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of blood pressure (mmHg)
  • Change from baseline in measurement of insulinemia (μU/mL) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of insulinemia (μU/mL)
  • Change from baseline in measurement of triglycerides (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of triglycerides (mg/dl)
  • 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)
  • Change from baseline in measurement of Glycated Haemoglobin (%) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of Glycated Haemoglobin (%)
  • Changes in bone mineral density [ Time Frame: 0, + 12 months, +24 months ]
    Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)]
  • 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.
  • 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.
  • 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.
  • 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)
  • 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).
  • 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)
  • Changes in androgens levels [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of androstenedione/testosterone ratio
  • Changes in sperm concentration [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Evaluation of sperm concentration according to WHO criteria
  • Changes in ovarian follicles reserve [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Evaluation of number of ovarian follicles by conventional ultrasound imaging
Original Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2018)
  • Change from baseline in measurement of glycaemia (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of glycaemia (mg/dl)
  • Change from baseline in measurement of BMI (Kg/m2) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of BMI (Kg/m2)
  • Change from baseline in measurement of blood pressure (mmHg) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of blood pressure (mmHg)
  • Change from baseline in measurement of insulinemia (μU/mL) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of insulinemia (μU/mL)
  • Change from baseline in measurement of triglycerides (mg/dl) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of triglycerides (mg/dl)
  • 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)
  • Change from baseline in measurement of Glycated Haemoglobin (%) [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of Glycated Haemoglobin (%)
  • Changes in bone mineral density [ Time Frame: 0, + 12 months, +24 months ]
    Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)]
  • Changes in quality of life [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Quality of life will be measured by AddiQol questionnaire
  • 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
  • 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
  • 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
  • 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
  • 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 CTCAE v4.0
  • Changes in androgens levels [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Measure of androstenedione/testosterone ratio
  • Changes in sperm concentration [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Evaluation of sperm concentration according to WHO criteria
  • Changes in number of ovarian follicles [ Time Frame: 0, + 6 months, + 12 months, +24 months ]
    Evaluation of number of ovarian follicles by conventional ultrasound imaging
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Congenital Adrenal Hyperplasia Once Daily Hydrocortisone Treatment
Official Title  ICMJE Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Congenital Adrenal Hyperplasia
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Dual-release hydrocortisone
    Interventions:
    • Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone)
    • Drug: Dual release hydrocortisone (plenadren)
  • Active Comparator: Conventional glucocorticoids
    Intervention: Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2018)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rosario Pivonello, M.D., PhD, Professor +390817464983 rosario.pivonello@unina.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03760835
Other Study ID Numbers  ICMJE 140/16
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Prof. Rosario Pivonello, Federico II University
Study Sponsor  ICMJE Federico II University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Federico II University
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP