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

• ClinicalTrials.gov Identifier: NCT02282150
• Recruitment Status: Unknown
• First Posted: November 4, 2014
• Last Update Posted: February 23, 2017
• Sponsor: Ulla Feldt-Rasmussen
• Information provided by (Responsible Party): Ulla Feldt-Rasmussen, Rigshospitalet, Denmark

Tracking Information

• First Submitted Date: October 26, 2014
• First Posted Date: November 4, 2014
• Last Update Posted Date: February 23, 2017
• Study Start Date: October 2016
• Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 3, 2014)

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 Measures: Same as current

Current Secondary Outcome Measures (submitted: November 3, 2014)

• 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 Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Modified-release Compared to Conventional Hydrocortisone on Diurnal Fatigue in Secondary Hypoadrenalism
• 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 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 Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Cross over

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Adrenal Insufficiency

Intervention

• 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 Name: Modified-release hydrocortisone

Study Arms

Conventional vs modified hydrocortisone;

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

Interventions:

• Drug: Hydrocortisone
• Drug: Plenadren

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 3, 2014): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2017
• Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Exclusion Criteria:

• Pregnancy
• Breast feeding
• Acromegaly
• Cushing's Disease
• Diabetes Mellitus
• Other major confounding disease
• Known or expected hypersensitivity to any of the excipients
• Lack of compliance (attendance and medication)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02282150
• Other Study ID Numbers: PLEN-EMA-hypo; 2014-002039-32 ( EudraCT Number ); H-1-2014-073 ( Other Identifier: Health Research Ethics in Capital Region of Denmark )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Ulla Feldt-Rasmussen, Rigshospitalet, Denmark
• Study Sponsor: Ulla Feldt-Rasmussen
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ulla Feldt-Rasmussen, MD, DMSc; Rigshospitalet, Denmark

• PRS Account: Rigshospitalet, Denmark
• Verification Date: February 2017