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A Pilot Study of the Normative Range of Overnight Urinary Free Cortisol Corrected for Creatinine in Children

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Abstract

Background

For more than a decade, urinary free cortisol corrected for creatinine (OUFCC) has been used to assess the systemic bioactivity of inhaled corticosteroids in children with asthma. Paediatric normative ranges, however, have not been established. The aim of the present study was to define a preliminary range for OUFCC in Tanner stage 1 children.

Methods

A post hoc analysis was performed of 26 Tanner stage one children (aged 5–11 years) with mild asthma only requiring prn (pro re nata) treatment with short-acting β2-agonists, who participated in a 3-way cross-over knemometry study. The study comprised a run-in, two washout periods and three treatment periods (2 weeks each). Urine was collected at the end of each period. A normative range was derived using the 95% prediction interval for the geometric mean OUFCC, calculated from run-in and washout periods.

Results

Twenty-six children contributed 41 OUFCC values. The geometric mean OUFCC was 9.0 nmol/mmol (95% PI: 3.6, 22.7 nmol/mmol).

Conclusions

The OUFCC preliminary normative range was 3.6 to 22.7 nmol/mmol in Tanner stage one children. A larger study in healthy children is warranted to confirm these findings and to assess potential differences in OUFCC across developmental stages and age groups, and by gender and race.

EudraCT number

2013-004719-32,

ClinicalTrials.gov identifier

NCT02063139

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Acknowledgements

The authors would like to thank study participants and nurses Signe Dreier and Anne Karina Kjaer for help with recruiting and taking care of the children in the study. This work was funded by Mundipharma Research Limited, Cambridge, United Kingdom.

Author information

Authors and Affiliations

  1. Asthma and Allergy Clinic, Children’s Clinic Randers, Dytmaersken 9, 8900, Randers, Denmark

    Ole D. Wolthers

  2. Biostatistics and Clinical Data Science, Mundipharma Research GmbH & Co. KG, Limburg, Germany

    Sabine Mersmann

  3. Medical Science, Mundipharma Research Limited, Cambridge, UK

    Sanjeeva Dissanayake

Authors
  1. Ole D. Wolthers
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  2. Sabine Mersmann
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  3. Sanjeeva Dissanayake
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Contributions

Ole D. Wolthers was the Principal Investigator for the study; Sabine Mersmann was the study Statistician, and Sanjeeva Dissanayake was the Clinical Lead. Sanjeeva Dissanayake drafted the manuscript and Ole D. Wolthers and Sabine Mersmann commented on it. All authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Corresponding author

Correspondence to Ole D. Wolthers.

Ethics declarations

Funding

The parent study upon which this research was based was sponsored by Mundipharma Research Ltd.

Conflict of interest

Ole D. Wolthers was the Principal Investigator for this study. Sabine Mersmann and Sanjeeva Dissanayake were full-time employees of the study sponsor, Mundipharma Research Ltd at the time the study was undertaken. The authors have no other financial relationships relevant to this article to disclose.

Ethics approval

The study was conducted in accordance with the International Guidelines issued by the European Commission in 1990 and the Declaration of Helsinki and approved by the Danish Health and Medicines Authority and Ethics Committee Region Midtjylland. Written informed consent was obtained from both parents/guardians, and assent from the child, before any trial procedure was carried out.

Trade mark statements

® FLUTIFORM is a registered trade mark of Jagotec AG. AEROCHAMBER PLUS and FLOW-VU are registered trade-marks of Trudell. Medical International. FLIXOTIDE and VOLUMATIC are registered trade-marks of Glaxo Group Limited. AEROBEC is a registered trade mark in Europe of either Meda AB or Teva Pharmaceuticals International GmbH. QVAR and AIROMIR are registered trade-marks in Europe of either IVAX International GmbH, Teva Pharmaceuticals International GmbH or 3M Company. AUTOHALER is a registered trade mark of 3M Company. COAT-A-COUNT is a registered trade mark in the United States of Siemens Healthcare Diagnostics Inc.

Additional information

S. Dissanayake: Address at the time this study was conducted

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Wolthers, O.D., Mersmann, S. & Dissanayake, S. A Pilot Study of the Normative Range of Overnight Urinary Free Cortisol Corrected for Creatinine in Children. Clin Drug Investig 38, 313–318 (2018). https://doi.org/10.1007/s40261-017-0609-x

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