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

Sponsor

Ulla Feldt-Rasmussen (Other)

Overall Status

Unknown status

CT.gov ID

NCT02282150

Collaborator

(none)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Adrenal Insufficiency	Drug: Hydrocortisone Drug: Plenadren	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Cross overCross over

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2016

Anticipated Primary Completion Date :

Nov 1, 2017

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Conventional vs modified hydrocortisone; 5 weeks of conventional hydrocortisone followed by 16 weeks of modified-release hydrocortisone (Plenadren)	Drug: Hydrocortisone Usual hydrocortisone dosage regimen; 10-40 mg hydrocortisone administered twice or thrice daily for 5 weeks Drug: Plenadren 10-40 mg modified-release hydrocortisone in tablets, once a day for 16 weeks Other Names: Modified-release hydrocortisone

Arm

Intervention/Treatment

Other: Conventional vs modified hydrocortisone;

5 weeks of conventional hydrocortisone followed by 16 weeks of modified-release hydrocortisone (Plenadren)

Drug: Hydrocortisone

Usual hydrocortisone dosage regimen; 10-40 mg hydrocortisone administered twice or thrice daily for 5 weeks

Drug: Plenadren

10-40 mg modified-release hydrocortisone in tablets, once a day for 16 weeks

Other Names:

Modified-release hydrocortisone

Outcome Measures

Primary Outcome Measures

Ecological Momentary Assessment (EMA) fatigue profiles [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

Secondary Outcome Measures

Quality of Life questionnaires [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) [At baseline and after 16 weeks of Plenadren (intervention) treatment]
Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed with adrenal insufficiency due to hypopituitarism
In steady twice or thrice daily (10-40 mg) hydrocortisone replacement treatment
Written informed consent
For women: Use of reliable methods of contraception in clinical trials in accordance with the definition by the Danish Health and Medicines Authority; intrauterine devices or hormonal methods (oral contraceptives, contraceptive implants, transdermal patches, hormonal vaginal devices or injections with prolonged release).