Adrenal InsufficiencyPhase 4PlenadrEMANCT02282150
Modified-release Compared to Conventional Hydrocortisone on Diurnal Fatigue in Secondary Hypoadrenalism
A Phase 4 study testing Hydrocortisone and Plenadren in people with Adrenal Insufficiency, run by Ulla Feldt-Rasmussen.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adrenal Insufficiency
- What is being tested?
- Hydrocortisone and Plenadren
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Oct 2016to Dec 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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)
About this study
Official title: Effect of Modified-release Compared to Conventional Hydrocortisone on Fatigue, Measured by Ecological Momentary Assessments; a Pilot Study.
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).
Read the 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.
- Conditions
- Adrenal Insufficiency
- Being tested
- Hydrocortisone, Plenadren
- Keywords
- Fatigue, Quality of Life, Hydrocortisone, Ecological Momentary Assessments
- Medical subject headings
- Adrenal Insufficiency, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Usual hydrocortisone dosage regimen; 10-40 mg hydrocortisone administered twice or thrice daily for 5 weeks
PlenadrenDrug
Also called Modified-release hydrocortisone
10-40 mg modified-release hydrocortisone in tablets, once a day for 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Conventional vs modified hydrocortisone; | Other | 5 weeks of conventional hydrocortisone followed by 16 weeks of modified-release hydrocortisone (Plenadren) Receives: Drug: Hydrocortisone; Drug: Plenadren |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ecological Momentary Assessment (EMA) fatigue profiles
Differences and variability of standard treatment vs. modified release hydrocortisone EMA fatigue profiles
Measured: 25 days during conventional hydrocortisone treatment and for 25 days during Plenadren (intervention) treatment
Secondary outcomes (2)
Quality of Life questionnaires
Fatigue Impact Scale (FIS), AD-specific quality-of-life questionnaire (AddiQol) and the Short Form Health Survey (SF-36)
Measured: At baseline and after 16 weeks of Plenadren (intervention) treatment
Safety (Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol)
Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol
Measured: At baseline and after 16 weeks of Plenadren (intervention) treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2014 (estimated)
- Study startOct 2016
- Primary completionNov 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adrenal InsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Cross over
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ulla Feldt-Rasmussen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ulla Feldt-Rasmussen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Ulla Feldt-Rasmussen, MD, DMSc, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02282150
- Sponsor's protocol ID
- PLEN-EMA-hypo
- Other IDs
- 2014-002039-32, H-1-2014-073, 2014
- Acronym
- PlenadrEMA
- Status last verified
- Feb 2017
- First submitted
- 26 Oct 2014
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Modified-release Compared to Conventional Hydrocortisone on Fatigue, Measured by Ecological Momentary Assessments; a Pilot Study.
- ClinicalTrials.gov ID
- NCT02282150
- Acronym / sponsor ID
- PlenadrEMA / PLEN-EMA-hypo
- Conditions
- Adrenal Insufficiency
- Keywords
- Fatigue, Quality of Life, Hydrocortisone, Ecological Momentary Assessments
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Ulla Feldt-RasmussenUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- Nov 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 4 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Cross over
| Arm | Type | Receives |
|---|---|---|
| Conventional vs modified hydrocortisone; | Other | Drug: Hydrocortisone, Drug: Plenadren5 weeks of conventional hydrocortisone followed by 16 weeks of modified-release hydrocortisone (Plenadren) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (8 listed)
- Pregnancy
- Breast feeding
- Acromegaly
- Cushing's Disease
- Diabetes Mellitus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrocortisoneUsual hydrocortisone dosage regimen; 10-40 mg hydrocortisone administered twice or thrice daily for 5 weeks | Drug | Conventional vs modified hydrocortisone; |
| PlenadrenAlso: Modified-release hydrocortisone10-40 mg modified-release hydrocortisone in tablets, once a day for 16 weeks | Drug | Conventional vs modified hydrocortisone; |
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
2 secondary outcomes
Quality of Life questionnaires
Time frame: At baseline and after 16 weeks of Plenadren (intervention) treatment
Safety (Biochemical parameters, DEXA scan, 24 hour blood pressure and salivary cortisol)
Time frame: At baseline and after 16 weeks of Plenadren (intervention) treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ulla Feldt-Rasmussen, MD, DMSc principal investigator
Copenhagen University Hospital, Rigshospitalet
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydrocortisone and Plenadren in people with Adrenal Insufficiency, run by Ulla Feldt-Rasmussen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ecological Momentary Assessment (EMA) fatigue profiles (time frame: 25 days during conventional hydrocortisone treatment and for 25 days during Plenadren (intervention) treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2017.