Adrenal InsufficiencyPhase 2VapredaNCT02689960
Vaginal Prednisone Administration for Prevention of Adrenal Crisis
A Phase 2 study testing 100mg prednisone suppository in people with Adrenal Insufficiency, run by Wuerzburg University Hospital.
Trial summary
Patients with chronic adrenal insufficiency need to adapt their glucocorticoid replacement dose in conditions of physical or psychological stress to prevent life threatening adrenal crisis. In cases of more severe impairment or unsecure gastrointestinal absorption (e.g. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Adrenal Insufficiency
- What is being tested?
- 100mg prednisone suppository
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to 1 Jun 2017
- Phase
- Phase 2
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients with chronic primary adrenal insufficiency due to autoimmune adrenalitis or bilateral adrenalectomy (disease duration at least 6 months)
- Age ≥ 18 years
- Patient´s written informed consent
- Ability to comply with the protocol procedures
- Established stable replacement therapy, no anticipated change in medication
- Negative pregnancy test and contraception (besides oral contraceptive pill) in pre-menopausal females
Who cannot join
- Diabetes mellitus
- Infectious disease with fever at time of investigation
- Known intolerance to the study drug or constituents
- Oral contraception
- Pregnancy or breast feeding
- Renal failure (creatinine >2.5 ULN)
- Disposition to vaginal mycosis (requiring treatment in the last 6 months or of necessity >2 antimycotic therapies/year)
- Recurrent urinary tract infections (of necessity >2 antibiosis therapies/year)
About this study
Official title: Vaginal Prednisone Administration for Prevention of Adrenal Crisis - a Bioequivalence Study
Patients with chronic adrenal insufficiency need to adapt their glucocorticoid replacement dose in conditions of physical or psychological stress to prevent life threatening adrenal crisis. In cases of more severe impairment or unsecure gastrointestinal absorption (e.g. gastroenteritis, severe infectious disease), rapid and highly dosed administration of glucocorticoids is crucial. The study is conducted to offer female patients the possibility to perform efficient prednisone self-administration in emergency situations in a way of administration, which is easy to perform and accepted by the patients. Therefore, pharmacokinetics and safety of vaginal prednisone administration will be studied and compared to rectal administration.
Read the detailed description
As patients with adrenal insufficiency still die from adrenal crisis, improvement of both prevention and also emergency management is needed. It is clear that perfect equipment and education of patients is key for further crisis prevention and management. Vaginal administration of prednisone-suppositories is easy to perform and independent of the gastro-intestinal system. Thus, this study aims at the efficacy, feasibility and safety of vaginal administration of prednisone-suppositories.
Recruitment:
Patients with primary adrenal insufficiency will be recruited. The adrenal insufficiency registry of Würzburg comprises more than 150 patients with primary adrenal insufficiency. Several patients have already indicated their interest to participate in the study. According to the European Medicines Agency (EMA) notes for guidance on the investigation of bioavailability and bioequivalence the number of 12 participants is regarded as the minimum required number.
Trial flow:
Pharmacokinetic studies will be performed at two different study visits. Patients will receive a 100mg prednisone suppository (Rectodelt® 100 mg) vaginal and rectal on two different study visits (interval longer then one week). Blood samples for determination of prednisone and adrenocorticotropic Hormone (ACTH) levels will be collected over a time period of 6 hours. Patients receive a diary to document eventual local or systemic adverse events during the following 7 days.
Stopping rules:
Participation of patients is fully voluntarily. Patients are able to stop participation in the study at any point in time. In addition, patients might claim the elimination of all data material at any point in time. Furthermore, study participation will be stopped for the individual patient, if new safety issues occur (e. g. new diagnosis of Diabetes mellitus, pregnancy or acute infectious disease) during the study. Relevant risks to the patients are highly unlikely. However, if 2 or more patients experience serious adverse events associated with the vaginal administration of prednisone with high likelihood, the study will be stopped.
Written informed consent:
A consent document including patient information upon the nature, scope and possible consequence of the trial must have been approved by the Institutional Review Board. Patients amenable for inclusion in the trial will be given sufficient time to study the written information, as well as possibility to ask questions before signing the consent document.
Analysis:
Documentation and analysis will be performed at the Department of Medicine I, Endocrine and Diabetes Unit, University of Würzburg, Germany. Data will be documented after pseudonymisation in a data base. Data analysis is mainly descriptive (bioequivalence of vaginal prednisone administration compared to rectal application, estimation of the patients regarding convenience and tolerability of different modes of drug administration, safety aspects).
Safety:
In the course of the trial, changes in physical findings as well as clinical signs and symptoms that may reflect adverse effects will be documented. Furthermore, all adverse events will be documented on the appropriate report form. When an adverse event occurs it will be graded according to the National cancer Institute - common toxicity criteria (NCI-CTC) (version 4.0). Patients receive a diary to document any local or systemic adverse event during the following 7 days after intervention. In addition, patients will be contacted by phone 3(±1) and 7(±1) days after vaginal administration of prednisone. If patients report any adverse events that are possibly related to the vaginal administration route, they will be called-in for further physical examination and detailed documentation. To further enhance individual patient's safety during the study, a safety assessment will be performed prior to the subsequent intervention. In addition, a safety assessment will be performed after 4 and 8 subsequent vaginal administrations of prednisone with evaluation of events during the 7 day follow up period after administration.
- Conditions
- Adrenal Insufficiency
- Being tested
- 100mg prednisone suppository
- Keywords
- addison disease, adrenal crisis, prednisone
- Medical subject headings
- Adrenal Insufficiency, Addison Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
100mg prednisone suppositoryDrug
Also called Rectodelt (approval number 6329964.00.00)
vaginal administration of 100mg prednisone suppository (Rectodelt)
| Study group | Role | What they receive |
|---|---|---|
| vaginal administration first | Other | Intervention first visit: vaginal administration of 100mg prednisone suppository, Intervention second visit: rectal administration of 100mg prednisone suppository Receives: Drug: 100mg prednisone suppository |
| rectal administration first | Other | Intervention first visit: rectal administration of 100mg prednisone suppository, Intervention second visit: vaginal administration 100mg prednisone suppository Receives: Drug: 100mg prednisone suppository |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bioequivalence of vaginal prednisone administration compared to rectal application, assessed by repeated determination of prednisolon levels (in blood)
The hypothesis is that the same prednisolone levels can be achieved within the same time frame after vaginale administration compared to rectal application.
Measured: up to 12 months
Secondary outcomes (3)
Safety of the vaginal administration of prednisone compared to rectal application, assessed by the number of participants with treatment-related adverse events (using the NCI-CTC, version 4.0).
Measured: up to 12 months
Suppressive effects on ACTH levels after vaginal administration of prednisone compared to rectal application, assessed by repeated determination of ACTH-levels
ACTH-levels are measured in plasma
Measured: up to 1 week
Tolerability by the patients assessed by a questionnaire
Questions record the preference of the patients between vaginal and rectal application.
Measured: up to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study startJan 2017
- Primary completionApr 2017
- Study completion1 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wuerzburg University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stefanie Hahner, MD, Prof., Principal investigator, Wuerzburg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02689960
- Sponsor's protocol ID
- Vapreda
- Acronym
- Vapreda
- Status last verified
- May 2017
- First submitted
- 8 Feb 2016
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 Feb;100(2):407-16. doi: 10.1210/jc.2014-3191. Epub 2014 Nov 24.
PubMed 25419882Hahner S, Hemmelmann N, Quinkler M, Beuschlein F, Spinnler C, Allolio B. Timelines in the management of adrenal crisis - targets, limits and reality. Clin Endocrinol (Oxf). 2015 Apr;82(4):497-502. doi: 10.1111/cen.12609. Epub 2014 Nov 6.
PubMed 25200922Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, Ventz M, Quinkler M, Allolio B. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 Mar;162(3):597-602. doi: 10.1530/EJE-09-0884. Epub 2009 Dec 2.
PubMed 19955259Hahner S, Burger-Stritt S, Allolio B. Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency. Eur J Endocrinol. 2013 Jun 29;169(2):147-54. doi: 10.1530/EJE-12-1057. Print 2013 Aug.
PubMed 23672956Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015 Mar;172(3):R115-24. doi: 10.1530/EJE-14-0824. Epub 2014 Oct 6.
PubMed 25288693Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan;84(1):17-22. doi: 10.1111/cen.12865. Epub 2015 Aug 27.
PubMed 26208266Anderson M, Kutzner S, Kaufman RH. Treatment of vulvovaginal lichen planus with vaginal hydrocortisone suppositories. Obstet Gynecol. 2002 Aug;100(2):359-62. doi: 10.1016/s0029-7844(02)02117-8.
PubMed 12151163
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaginal Prednisone Administration for Prevention of Adrenal Crisis - a Bioequivalence Study
- ClinicalTrials.gov ID
- NCT02689960
- Acronym / sponsor ID
- Vapreda / Vapreda
- Conditions
- Adrenal Insufficiency
- Keywords
- addison disease, adrenal crisis, prednisone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Wuerzburg University HospitalUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- 1 Jun 2017 (actual)
- First posted
- 24 Feb 2016 (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.
Patients with chronic adrenal insufficiency need to adapt their glucocorticoid replacement dose in conditions of physical or psychological stress to prevent life threatening adrenal crisis. In cases of more severe impairment or unsecure gastrointestinal absorption (e.g. gastroenteritis, severe infectious disease), rapid and highly dosed administration of glucocorticoids is crucial. The study is conducted to offer female patients the possibility to perform efficient prednisone self-administration in emergency situations in a way of administration, which is easy to perform and accepted by the patients. Therefore, pharmacokinetics and safety of vaginal prednisone administration will be studied and compared to rectal administration.
Detailed description
As patients with adrenal insufficiency still die from adrenal crisis, improvement of both prevention and also emergency management is needed. It is clear that perfect equipment and education of patients is key for further crisis prevention and management. Vaginal administration of prednisone-suppositories is easy to perform and independent of the gastro-intestinal system. Thus, this study aims at the efficacy, feasibility and safety of vaginal administration of prednisone-suppositories.
Recruitment:
Patients with primary adrenal insufficiency will be recruited. The adrenal insufficiency registry of Würzburg comprises more than 150 patients with primary adrenal insufficiency. Several patients have already indicated their interest to participate in the study. According to the European Medicines Agency (EMA) notes for guidance on the investigation of bioavailability and bioequivalence the number of 12 participants is regarded as the minimum required number.
Trial flow:
Pharmacokinetic studies will be performed at two different study visits. Patients will receive a 100mg prednisone suppository (Rectodelt® 100 mg) vaginal and rectal on two different study visits (interval longer then one week). Blood samples for determination of prednisone and adrenocorticotropic Hormone (ACTH) levels will be collected over a time period of 6 hours. Patients receive a diary to document eventual local or systemic adverse events during the following 7 days.
Stopping rules:
Participation of patients is fully voluntarily. Patients are able to stop participation in the study at any point in time. In addition, patients might claim the elimination of all data material at any point in time. Furthermore, study participation will be stopped for the individual patient, if new safety issues occur (e. g. new diagnosis of Diabetes mellitus, pregnancy or acute infectious disease) during the study. Relevant risks to the patients are highly unlikely. However, if 2 or more patients experience serious adverse events associated with the vaginal administration of prednisone with high likelihood, the study will be stopped.
Written informed consent:
A consent document including patient information upon the nature, scope and possible consequence of the trial must have been approved by the Institutional Review Board. Patients amenable for inclusion in the trial will be given sufficient time to study the written information, as well as possibility to ask questions before signing the consent document.
Analysis:
Documentation and analysis will be performed at the Department of Medicine I, Endocrine and Diabetes Unit, University of Würzburg, Germany. Data will be documented after pseudonymisation in a data base. Data analysis is mainly descriptive (bioequivalence of vaginal prednisone administration compared to rectal application, estimation of the patients regarding convenience and tolerability of different modes of drug administration, safety aspects).
Safety:
In the course of the trial, changes in physical findings as well as clinical signs and symptoms that may reflect adverse effects will be documented. Furthermore, all adverse events will be documented on the appropriate report form. When an adverse event occurs it will be graded according to the National cancer Institute - common toxicity criteria (NCI-CTC) (version 4.0). Patients receive a diary to document any local or systemic adverse event during the following 7 days after intervention. In addition, patients will be contacted by phone 3(±1) and 7(±1) days after vaginal administration of prednisone. If patients report any adverse events that are possibly related to the vaginal administration route, they will be called-in for further physical examination and detailed documentation. To further enhance individual patient's safety during the study, a safety assessment will be performed prior to the subsequent intervention. In addition, a safety assessment will be performed after 4 and 8 subsequent vaginal administrations of prednisone with evaluation of events during the 7 day follow up period after administration.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| vaginal administration first | Other | Drug: 100mg prednisone suppositoryIntervention first visit: vaginal administration of 100mg prednisone suppository, Intervention second visit: rectal administration of 100mg prednisone suppository |
| rectal administration first | Other | Drug: 100mg prednisone suppositoryIntervention first visit: rectal administration of 100mg prednisone suppository, Intervention second visit: vaginal administration 100mg prednisone suppository |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Female patients with chronic primary adrenal insufficiency due to autoimmune adrenalitis or bilateral adrenalectomy (disease duration at least 6 months)
- Age ≥ 18 years
- Patient´s written informed consent
- Ability to comply with the protocol procedures
- Established stable replacement therapy, no anticipated change in medication
Key exclusion criteria (8 listed)
- Diabetes mellitus
- Infectious disease with fever at time of investigation
- Known intolerance to the study drug or constituents
- Oral contraception
- Pregnancy or breast feeding
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 |
|---|---|---|
| 100mg prednisone suppositoryAlso: Rectodelt (approval number 6329964.00.00)vaginal administration of 100mg prednisone suppository (Rectodelt) | Drug | rectal administration first, vaginal administration first |
Primary outcome
Bioequivalence of vaginal prednisone administration compared to rectal application, assessed by repeated determination of prednisolon levels (in blood)
Time frame: up to 12 months
The hypothesis is that the same prednisolone levels can be achieved within the same time frame after vaginale administration compared to rectal application.
3 secondary outcomes
Safety of the vaginal administration of prednisone compared to rectal application, assessed by the number of participants with treatment-related adverse events (using the NCI-CTC, version 4.0).
Time frame: up to 12 months
Suppressive effects on ACTH levels after vaginal administration of prednisone compared to rectal application, assessed by repeated determination of ACTH-levels
Time frame: up to 1 week
Tolerability by the patients assessed by a questionnaire
Time frame: up to 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Background: PubMed 25419882Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 Feb;100(2):407-16. doi: 10.1210/jc.2014-3191. Epub 2014 Nov 24.
- Background: PubMed 25200922Hahner S, Hemmelmann N, Quinkler M, Beuschlein F, Spinnler C, Allolio B. Timelines in the management of adrenal crisis - targets, limits and reality. Clin Endocrinol (Oxf). 2015 Apr;82(4):497-502. doi: 10.1111/cen.12609. Epub 2014 Nov 6.
- Background: PubMed 19955259Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, Ventz M, Quinkler M, Allolio B. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 Mar;162(3):597-602. doi: 10.1530/EJE-09-0884. Epub 2009 Dec 2.
- Background: PubMed 23672956Hahner S, Burger-Stritt S, Allolio B. Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency. Eur J Endocrinol. 2013 Jun 29;169(2):147-54. doi: 10.1530/EJE-12-1057. Print 2013 Aug.
- Background: PubMed 25288693Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015 Mar;172(3):R115-24. doi: 10.1530/EJE-14-0824. Epub 2014 Oct 6.
- Background: PubMed 26208266Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan;84(1):17-22. doi: 10.1111/cen.12865. Epub 2015 Aug 27.
- Background: PubMed 12151163Anderson M, Kutzner S, Kaufman RH. Treatment of vulvovaginal lichen planus with vaginal hydrocortisone suppositories. Obstet Gynecol. 2002 Aug;100(2):359-62. doi: 10.1016/s0029-7844(02)02117-8.
- Individual participant dataSharing planned: Yes
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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.
Stefanie Hahner, MD, Prof. principal investigator
Wuerzburg University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 100mg prednisone suppository in people with Adrenal Insufficiency, run by Wuerzburg University Hospital.
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 6 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: finished, as of the sponsor's last update on 20 Jun 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Bioequivalence of vaginal prednisone administration compared to rectal application, assessed by repeated determination of prednisolon levels (in blood) (time frame: up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02689960, which also lists 7 linked publications.
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 20 Jun 2017.