Major Depressive DisorderPhase 2NCT00125554
Metyrapone as Additive Treatment in Major Depression
A Phase 2 study testing Metyrapone in people with Major Depressive Disorder, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
Trial summary
The purpose of this study is to test whether metyrapone is an effective and safe augmenting agent in the treatment of major depression. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Metyrapone
- How many people
- 63 participants
- Where
- 1 siteGermany
- Study dates
- May 1998to Jul 2001
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of major depressive disorder; single or recurrent according to DSM-IV criteria (296.2 or 296.3)
- A minimum baseline Hamilton score of 18 points on the Hamilton Rating Scale for Depression (HamD; 21-item version)
- Age from 18 to 75 years
- A drug free period of at least 5 days from antidepressants, antipsychotics, mood stabilizers and all other medications except for mild antihypertensive agents
- A negative urinary drug screening diagnosis
Who cannot join
- A current DSM-IV diagnosis for other axis I psychiatric disorders
- Serious medical conditions, especially those associated with adrenal insufficiency
- Pregnancy, nursing or refusal to use a reliable method of birth control in women.
- Participants were randomly assigned to a study group if they met these criteria.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Dept. of Psychiatry and Psychotherapy, UKE
Hamburg, Free and Hanseatic City of Hamburg, 20246
About this study
Official title: Double-Blind, Placebo Controlled Trial of Metyrapone as Augmenting Agent in the Treatment of Major Depression
The purpose of this study is to test whether metyrapone is an effective and safe augmenting agent in the treatment of major depression.
Read the detailed description
The investigators' understanding of the neuroendocrine pathophysiology of depression has made significant progress in recent years, which should help to develop new remedies. Alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis are the most consistent pathological endocrine findings in depression. Hence, attempts have been made to treat depression by directly targeting HPA-axis activity. Currently, three major pathways are investigated:
- Administration of CRH-antagonists;
- Administration of glucocorticoid-receptor-antagonists; and
- Treatment with steroid-synthesis inhibitors like ketoconazole, aminogluthethimide or metyrapone.
The investigators' aim was to conduct the first prospective, randomized, placebo-controlled, double-blind clinical trial of metyrapone as additive treatment in depression. Metyrapone was preferred, since this compound inhibits selectively the 11β-hydroxylase and the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), thereby exerting direct effects within the central nervous system (CNS). The additive approach was applied because the intended inclusion of severely depressed patients made a pure placebo group ethically challenging. Furthermore, the continuous use of an antidepressant allowed a standardized follow up after the double-blind period.
The hypotheses to be tested were, whether metyrapone exerts potentiating effects during a standard antidepressant therapy and whether an earlier onset-of-action and an improved overall and sustained treatment response can be achieved. Since GR/MR distribution as well as 11β-HSD-1 activities are subject to sexual dimorphism in humans, the sample was prospectively stratified for gender and balanced for treatment with two selected serotonergic antidepressants, allowing further analysis of gender effects and neuroendocrine treatment effects.
- Conditions
- Major Depressive Disorder
- Being tested
- Metyrapone
- Keywords
- Clinical trial, double-blind, randomized placebo-controlled trial, metyrapone, Major Depression
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetyraponeDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Two psychometric criteria defined by the number of responders and time to onset-of-action. The number of responders was considered twice after 3 and 5 weeks by defining the treatment response as a 30% and 50% reduction
the course of concentrations of ACTH, cortisol, 11-deoxycortisol and DHEA.
Secondary outcomes (1)
Other psychometric scores, demographic parameters and side effects were considered as secondary variables.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2005 (estimated)
- Study startMay 1998
- Study completionJul 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 63 participants
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Investigators
- Holger Jahn, MD, Study director, University Hospital Hamburg-Eppendorf, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00125554
- Sponsor's protocol ID
- HH-PSY-ja-007
- Status last verified
- Jul 2005
- First submitted
- 29 Jul 2005
- Last updated
- 12 Aug 2005
- Results posted
- No
Publications
Jahn H, Schick M, Kiefer F, Kellner M, Yassouridis A, Wiedemann K. Metyrapone as additive treatment in major depression: a double-blind and placebo-controlled trial. Arch Gen Psychiatry. 2004 Dec;61(12):1235-44. doi: 10.1001/archpsyc.61.12.1235.
PubMed 15583115
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind, Placebo Controlled Trial of Metyrapone as Augmenting Agent in the Treatment of Major Depression
- ClinicalTrials.gov ID
- NCT00125554
- Acronym / sponsor ID
- HH-PSY-ja-007
- Conditions
- Major Depressive Disorder
- Keywords
- Clinical trial, double-blind, randomized placebo-controlled trial, metyrapone, Major Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Study start
- May 1998
- Study completion
- Jul 2001
- First posted
- 1 Aug 2005 (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.
The purpose of this study is to test whether metyrapone is an effective and safe augmenting agent in the treatment of major depression.
Detailed description
The investigators' understanding of the neuroendocrine pathophysiology of depression has made significant progress in recent years, which should help to develop new remedies. Alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis are the most consistent pathological endocrine findings in depression. Hence, attempts have been made to treat depression by directly targeting HPA-axis activity. Currently, three major pathways are investigated:
- Administration of CRH-antagonists;
- Administration of glucocorticoid-receptor-antagonists; and
- Treatment with steroid-synthesis inhibitors like ketoconazole, aminogluthethimide or metyrapone.
The investigators' aim was to conduct the first prospective, randomized, placebo-controlled, double-blind clinical trial of metyrapone as additive treatment in depression. Metyrapone was preferred, since this compound inhibits selectively the 11β-hydroxylase and the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), thereby exerting direct effects within the central nervous system (CNS). The additive approach was applied because the intended inclusion of severely depressed patients made a pure placebo group ethically challenging. Furthermore, the continuous use of an antidepressant allowed a standardized follow up after the double-blind period.
The hypotheses to be tested were, whether metyrapone exerts potentiating effects during a standard antidepressant therapy and whether an earlier onset-of-action and an improved overall and sustained treatment response can be achieved. Since GR/MR distribution as well as 11β-HSD-1 activities are subject to sexual dimorphism in humans, the sample was prospectively stratified for gender and balanced for treatment with two selected serotonergic antidepressants, allowing further analysis of gender effects and neuroendocrine treatment effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of major depressive disorder; single or recurrent according to DSM-IV criteria (296.2 or 296.3)
- A minimum baseline Hamilton score of 18 points on the Hamilton Rating Scale for Depression (HamD; 21-item version)
- Age from 18 to 75 years
- A drug free period of at least 5 days from antidepressants, antipsychotics, mood stabilizers and all other medications except for mild antihypertensive agents
- A negative urinary drug screening diagnosis
Key exclusion criteria (4 listed)
- A current DSM-IV diagnosis for other axis I psychiatric disorders
- Serious medical conditions, especially those associated with adrenal insufficiency
- Pregnancy, nursing or refusal to use a reliable method of birth control in women.
- Participants were randomly assigned to a study group if they met these criteria.
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 |
|---|---|---|
| Metyrapone | Drug | – |
Primary outcome
Two psychometric criteria defined by the number of responders and time to onset-of-action. The number of responders was considered twice after 3 and 5 weeks by defining the treatment response as a 30% and 50% reduction
the course of concentrations of ACTH, cortisol, 11-deoxycortisol and DHEA.
1 secondary outcome
Other psychometric scores, demographic parameters and side effects were considered as secondary variables.
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 12 Aug 2005.
- Results publication: PubMed 15583115Jahn H, Schick M, Kiefer F, Kellner M, Yassouridis A, Wiedemann K. Metyrapone as additive treatment in major depression: a double-blind and placebo-controlled trial. Arch Gen Psychiatry. 2004 Dec;61(12):1235-44. doi: 10.1001/archpsyc.61.12.1235.
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
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.
Holger Jahn, MD study director
University Hospital Hamburg-Eppendorf, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metyrapone in people with Major Depressive Disorder, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
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 5 inclusion and 4 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 12 Aug 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Two psychometric criteria defined by the number of responders and time to onset-of-action. The number of responders was considered twice after 3 and 5 weeks by defining the treatment response as a 30% and 50% reduction. The study lists 2 primary outcomes in all. 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 NCT00125554, which also lists 1 linked publication.
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 12 Aug 2005.