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The effect of dual-release versus conventional hydrocortisone on fatigue, measured by ecological momentary assessments

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Abstract

Purpose

Replicating the physiological cortisol secretion is key in the treatment of glucocorticoid insufficient individuals and optimization may enhance quality of life. The study investigates fatigue measured by ecological momentary assessments in patients treated with conventional hydrocortisone compared with once-daily dual-release hydrocortisone (Plenadren).

Methods

A 21-week open-label switch pilot trial included 30 patients with adrenal insufficiency due to hypopituitarism. Fatigue was assessed four times daily for 20 days using a momentary item version of the Multidimensional Fatigue Inventory on patients’ usual hydrocortisone regimen. Participants switched treatment to an identical daily dose of Plenadren for 16 weeks where fatigue assessments were repeated. Change in fatigue and diurnal variation of fatigue was analyzed using mixed models for repeated measurements.

Results

In four out of five fatigue subscales fatigue was significantly reduced 0.7–1.1 points (scales ranging from 4 to 20), when treated with Plenadren compared with conventional hydrocortisone, corresponding to small effect sizes below the scale-specific minimal important changes. However, 33% of the participants completing the study (9/27) experienced reductions in fatigue above the minimal important change. On Plenadren, we found larger between-person variances and smaller within-person variances. Finally, we identified diurnal fatigue curves for both treatments.

Conclusions

The Plenadren-related reduction in fatigue was significant but not necessarily of clinical importance when looking at a group level. However, there was a large interindividual variation in treatment effect, why patients with a large benefit in quality of life should be identified. Future RCTs should be powered to detect the effect magnitudes identified here.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Funding

This investigator-initiated research was supported by a grant (IST-DNK-000718) from Shire International GmbH, a member of the Takeda group of companies. The project emanated from the Department of Medical Endocrinology at Copenhagen University Hospital Rigshospitalet and the trial group assume responsibility for all aspects of the study. UFR’s research salary is sponsored by a grant from Novo Nordisk Foundation.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Victor Brun Boesen, Stina Willemoes Borresen, Thea Christoffersen, Marianne Klose, Torquil Watt & Ulla Feldt-Rasmussen

  2. Department of Internal Medicine, Copenhagen University Hospital Herlev Gentofte, Gentofte, Denmark

    Torquil Watt

  3. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Torquil Watt & Ulla Feldt-Rasmussen

Authors
  1. Victor Brun Boesen
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  2. Stina Willemoes Borresen
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  3. Thea Christoffersen
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  4. Marianne Klose
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  5. Torquil Watt
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  6. Ulla Feldt-Rasmussen
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Corresponding author

Correspondence to Ulla Feldt-Rasmussen.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was performed in accordance with the Declarations of Helsinki and monitored by the Good Clinical Practice unit at Rigshospitalet. The study was approved by the Regional Scientific Ethical Committee in Copenhagen (ID: H-1-2014-073), the Danish Medicines Agency (ID: 2014070658), and the Danish Data Protection Agency (local identifier at Rigshospitalet: 30–1233). The study was registered at the EudraCT database (2014-002039-32). Informed consent was obtained from all individual participants.

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Boesen, V.B., Borresen, S.W., Christoffersen, T. et al. The effect of dual-release versus conventional hydrocortisone on fatigue, measured by ecological momentary assessments. Endocrine 71, 467–475 (2021). https://doi.org/10.1007/s12020-020-02507-x

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  • DOI: https://doi.org/10.1007/s12020-020-02507-x

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