Clinical Trial: Modified-release Compared to Conventional Hydrocortisone on Diurnal Fatigue in Secondary Hypoadrenalism

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Effect of Modified-release Compared to Conventional Hydrocortisone on Fatigue, Measured by Ecological Momentary Assessments; a Pilot Study.

Brief Summary: Despite optimized hydrocortisone replacement regimes, many patients with adrenal insufficiency (AI) suffer from impaired quality of life (QoL). Characteristically, patients report high fatigue levels at certain times during the day. A modified-release hydrocortisone has been shown to improve QoL, particularly fatigue, in patients with primary AI. However, it is unknown, if the same effect can be observed in patients with secondary AI. Further, no studies have evaluated the effect, taking into account the diurnal variation of fatigue. A novel survey method termed Ecological Momentary Assessments (EMA) has the potential to provide reliable measurements of diurnal variations in patient-reported outcomes, such as fatigue. We will compare the effect of modified-release compared to conventional hydrocortisone on fatigue in patients with secondary AI due to pituitary disease, and hereby assess the feasibility of EMA as outcome in future large-scale randomised clinical trials (RCTs).

Detailed Summary: The study is conducted as an open-label, single-arm, two-period, crossover pilot trial. Includible patients are observed for 5 weeks on their usual treatment (twice or thrice daily hydrocortisone). Assessments of QoL, in terms of EMA assessments, to be used as baseline measurement in the study, are collected for 20 days preceded by a 5 days technology adaptation phase. Thereafter participants are shifted to modified release hydrocortisone (Plenadren) once daily (OD), on a dose as per Summary of Product Characteristics (SmPC). Assessments of QoL to be used as outcome of intervention in the study are performed after 12.5 weeks after initiation of Plenadren intervention treatment, in order to take into consideration the period of re-adjustment of the body after the switch from conventional hydrocortisone to Plenadren. As done at the baseline observation, EMA measurement is preceded by a five days technology adaptation phase. At the end of the intervention treatment period, the patients will be shifted to their usual hydrocortisone treatment and will be followed at the outpatient clinic according to the directives of the clinic. Biochemical parameters; blood samples, DEXA scan, 24 hour blood pressure and salivary cortisol, will be assessed at baseline and after 16 weeks, as part of the safety evaluation of Plenadren.
Sponsor: Ulla Feldt-Rasmussen

Current Primary Outcome: Ecological Momentary Assessment (EMA) fatigue profiles [ Time Frame: 25 days during conventional hydrocortisone treatment and for 25 days during Plenadren (intervention) treatment ]

Differences and variability of standard treatment vs. modified release hydrocortisone EMA fatigue profiles


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Quality of Life questionnaires [ Time Frame: At baseline and after 16 weeks of Plenadren (intervention) treatment ]
    Fatigue Impact Scale (FIS), AD-specific quality-of-life questionnaire (AddiQol) and the Short Form Health Survey (SF-36)
  • Safety (Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol) [ Time Frame: At baseline and after 16 weeks of Plenadren (intervention) treatment ]
    Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol


Original Secondary Outcome: Same as current

Information By: Rigshospitalet, Denmark

Dates:
Date Received: October 26, 2014
Date Started: October 2016
Date Completion: December 2017
Last Updated: February 21, 2017
Last Verified: February 2017