PlenadrEMA: effect of dual-release versus conventional hydrocortisone on fatigue, measured by ecological momentary assessments: a study protocol for an open-label switch pilot study

TY - JOUR

T1 - PlenadrEMA

T2 - effect of dual-release versus conventional hydrocortisone on fatigue, measured by ecological momentary assessments: a study protocol for an open-label switch pilot study

AU - Boesen, Victor Brun

AU - Christoffersen, Thea

AU - Watt, Torquil

AU - Borresen, Stina Willemoes

AU - Klose, Marianne

AU - Feldt-Rasmussen, Ulla

N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - INTRODUCTION: Patients with adrenal insufficiency have impaired health-related quality of life (QoL). The dual-release hydrocortisone preparation, Plenadren, has been developed to mimic the physiological cortisol release more closely than conventional hydrocortisone treatment. Plenadren has been shown to improve QoL, in particular fatigue, in patients with primary adrenal insufficiency. However, the effect has not been investigated in patients with secondary adrenal insufficiency; furthermore, no study has taken the diurnal variation of fatigue into account. To assess diurnal variations, it is necessary to use repeated daily measurements, such as ecological momentary assessments (EMAs). This study aims to evaluate EMAs of fatigue as outcome in future large-scale randomised clinical trials.METHODS AND ANALYSIS: The PlenadrEMA trial is an investigator-initiated open-label switch pilot trial of the effect of Plenadren versus conventional hydrocortisone on fatigue in patients with secondary adrenal insufficiency. The trial will include 30 participants. After 5 weeks on their usual hydrocortisone treatment, patients will be shifted to Plenadren for 16 weeks. Fatigue will be assessed using momentary versions of the Multidimensional Fatigue Inventory (MFI-20). Items will be administered to participants via a smartphone application four times daily during 20 days. Assessments will be performed before treatment shift and repeated after 12.5 weeks on Plenadren. The study will identify the best suited outcome for future randomised clinical trials, and in addition, estimate the variability and difference in fatigue between the two treatments to perform power calculations.ETHICS AND DISSEMINATION: The trial will be conducted in accordance with the Declaration of Helsinki and has been approved by the Regional Scientific Ethical Committee in Copenhagen (ID: H-1-2014-073). All patients will receive written and verbal information about the trial and will give informed consent before enrolment. Findings will be published in peer-reviewed journals and presented at international conferences.TRIAL REGISTRATION NUMBER: EudraCT201400203932.

AB - INTRODUCTION: Patients with adrenal insufficiency have impaired health-related quality of life (QoL). The dual-release hydrocortisone preparation, Plenadren, has been developed to mimic the physiological cortisol release more closely than conventional hydrocortisone treatment. Plenadren has been shown to improve QoL, in particular fatigue, in patients with primary adrenal insufficiency. However, the effect has not been investigated in patients with secondary adrenal insufficiency; furthermore, no study has taken the diurnal variation of fatigue into account. To assess diurnal variations, it is necessary to use repeated daily measurements, such as ecological momentary assessments (EMAs). This study aims to evaluate EMAs of fatigue as outcome in future large-scale randomised clinical trials.METHODS AND ANALYSIS: The PlenadrEMA trial is an investigator-initiated open-label switch pilot trial of the effect of Plenadren versus conventional hydrocortisone on fatigue in patients with secondary adrenal insufficiency. The trial will include 30 participants. After 5 weeks on their usual hydrocortisone treatment, patients will be shifted to Plenadren for 16 weeks. Fatigue will be assessed using momentary versions of the Multidimensional Fatigue Inventory (MFI-20). Items will be administered to participants via a smartphone application four times daily during 20 days. Assessments will be performed before treatment shift and repeated after 12.5 weeks on Plenadren. The study will identify the best suited outcome for future randomised clinical trials, and in addition, estimate the variability and difference in fatigue between the two treatments to perform power calculations.ETHICS AND DISSEMINATION: The trial will be conducted in accordance with the Declaration of Helsinki and has been approved by the Regional Scientific Ethical Committee in Copenhagen (ID: H-1-2014-073). All patients will receive written and verbal information about the trial and will give informed consent before enrolment. Findings will be published in peer-reviewed journals and presented at international conferences.TRIAL REGISTRATION NUMBER: EudraCT201400203932.

KW - Adrenal Insufficiency/drug therapy

KW - Circadian Rhythm/drug effects

KW - Ecological Momentary Assessment

KW - Fatigue/etiology

KW - Humans

KW - Hydrocortisone/administration & dosage

KW - Hypopituitarism/complications

KW - Patient Safety

KW - Pilot Projects

KW - Quality of Life

KW - Research Design

KW - Smartphone

U2 - 10.1136/bmjopen-2017-019487

DO - 10.1136/bmjopen-2017-019487

M3 - Journal article

C2 - 29362269

SN - 2044-6055

VL - 8

SP - e019487

JO - BMJ Open

JF - BMJ Open

IS - 1

ER -