- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01375920
Antiglucocorticoid Augmentation of antiDepressants in Depression (ADD)
July 16, 2014 updated by: Jane Barnes
Depression is one of the most common mental health problems, with at least one in six adults suffering from this at some time in their life.
It can become long-lasting and frequently recurs.
Depression has a large negative impact on quality of life of patients and their carers and it has also been shown to be one of the leading causes of working age adults receiving disability payments in the UK.
The need for improved treatment has been recognised by the Department of Health and others.
Improvements in drug treatments are therefore required.
There has been recent increased understanding of some of the causes of the frequent lack of complete response seen with antidepressants.
The stress hormone, cortisol, is often elevated or poorly controlled in depression and there is laboratory and clinical research to show that this hormonal change reduces the benefits from antidepressants with associated poor outcome and memory problems.
Recently it has been shown in small studies that giving treatments that reduce cortisol or block its harmful effects for between 1 and 3 weeks overcome these negative consequences.
Our group is particularly interested and experienced in this topic.
The investigators plan to study a drug that decreases cortisol levels in people who have not recovered with standard antidepressants so that the investigators can find out the usefulness of this treatment (compared with placebo (dummy tablet)) in day to day life as well as checking closely for side-effects (the initial studies have shown that the particular drug the investigators wish to study (metyrapone) has few side effects).
The investigators will also measure cortisol and see if its level can tell us which people do best with this treatment.
The investigators will carry out this study in 3 centres across the UK.
The investigators will carry out some additional tests of specific sorts of memory and decision making and also do this while scanning the brain (in a painless test).
The results of these tests, along with tests of brain wave patterns, should help us understand more fully how this new treatment is working and who responds best to it.
The study will help us find out if this drug should be used more widely for people not responding to standard treatments and will also lead on to the development of other new treatments with an anti-cortisol effect to help tackle the major problem of poor outcome from depression.
Study Overview
Study Type
Interventional
Enrollment (Actual)
190
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Bradford, United Kingdom
- Bradford District Care Trust
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Leeds, United Kingdom, LS12 3QE
- Leeds Community Mental Health Team
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Manchester, United Kingdom, M13 9PT
- Affective Disorders Service
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Manchester, United Kingdom, M30 0GT
- Manchester Community Mental Health Team
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Manchester, United Kingdom
- Manchester Magnetic Resonance Centre
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Newcastle upon Tyne, United Kingdom, NE3 3XT
- Northumberland, Tyne and Wear NHS foundation trust
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Teesside
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Newcastle upon Tyne, Teesside, United Kingdom, TS17 6SD
- Stockton Affective Disorders Service
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Tyne and Wear
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Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
- Newcastle Community Mental Health Team
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Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
- Regional Affective Disorders Service
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Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE28 7PD
- North Tyneside Community Mental Health Team
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Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE4 5PL
- Newcastle Magnetic Resonance Centre
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Patient Inclusion Criteria:
- Depression Severity: Hamilton Depression Rating Scale (HDRS17) score ≥18, consistent with a moderate to severe episode. The stability of the patient's clinical state will also be assessed at week 0. A repeat HDRS17 score at time 0 is required ≥18 or greater.
- Treatment refractoriness: assessed using the Massachusetts General Hospital (MGH) staging method. This defines minimum effective doses of all currently-available antidepressants and an "adequate trial" as being for at least six weeks. For the trial to be considered a "failure", it must have been considered by the clinical team to have been ineffective rather, than the drug not having been taken or tolerated. Patients must have failed to have responded to at least their second trial of an antidepressant. This equates to a minimum score of two on MGH staging. The maximum MGH score for inclusion in the study will be 10. A UK study showed mean MGH scores in primary care patients of less than one, in secondary care mental health settings of around five and of 11 in a population of patients referred to a tertiary centre (Dr D Christmas, Dundee, Personal Communication).
- Current antidepressant treatment: patients must be taking monotherapy or combination antidepressant therapy which includes a serotonergic drug (an SSRI, a tertiary amine tricyclic, venlafaxine, duloxetine or mirtazapine). They must not be on noradrenergic antidepressant monotherapy (e.g. with lofepramine, imipramine or reboxetine). At the point of randomisation, patients must have been on their current antidepressant medication, at the current dose, for a minimum of four weeks.
- Age: 18-65. For the mechanistic sub-studies the patients upper age limit is 60.
Healthy Control Inclusion Criteria:
- Aged 18-60.
- Currently psychiatrically well, confirmed through SCID interview. HDRS17 score of ≤5, and no current psychotropic medication.
- No past history of psychiatric illness, as revealed by SCID interview, or requiring any treatment (formal psychotherapy or psychotropic medication).
- No first degree family history of psychiatric illness.
Patient Exclusion Criteria:
- Any other DSM IV Axis I disorder other than an anxiety disorder unless the depressive episode is considered to be secondary to the anxiety disorder, confirmed using the Structured Clinical Interview for DSM (SCID).
- Physical co-morbidity which would render the use of Metyrapone inappropriate, including untreated hypothyroidism, disorders of steroid production, current, severe cardiac failure, current, severe or frequent angina, current renal failure or myocardial infarction within the last year.
- Pregnancy, determined by history and, if indicated, urine pregnancy test.
- Mothers who are breastfeeding.
- Use of concomitant medication that would interfere, in a pharmacodynamic or pharmacokinetic manner, with Metyrapone.
- Dependence on alcohol or other drug in the past 12 months, and/or current harmful use of alcohol or other drug.
- Recently having taken part in another research study that could interfere with the results of this one.
Healthy Control Exclusion Criteria:
- Any physical ill health which would render the use of Metyrapone inappropriate, including untreated hypothyroidism, disorders of steroid production, current, severe cardiac failure, current, severe or frequent angina, current renal failure, or myocardial infarction within the last year. NOTE: healthy controls are NOT treated with Metyrapone.
- Pregnancy, determined by history and, if indicated, urine pregnancy test.
- Mothers who are breastfeeding.
- Use of any medication that would interfere, in a pharmacodynamic or pharmacokinetic manner, with Metyrapone.
- Dependence on alcohol or other drug in the past 12 months, and/or current harmful use of alcohol or other drug.
- Presence of any metal implants or foreign bodies such as from a surgical implant, accident or injury [this criteria only applies to those undergoing the fMRI scans - this is all 30 healthy subjects recruited in the North West (NW)and 15 of the 25 recruited in the North East (NE)].
- Recently having taken part in another research study that could interfere with the results of this one.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Metyrapone, daily medication
500 milligrams Metyrapone to be taken orally twice daily for 3 weeks.
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500 milligrams to be taken twice a day orally
Other Names:
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Placebo Comparator: placebo
a matched placebo will be given for patients to take twice daily
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a matched placebo will be administered to patients to take twice a day for 3 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The primary outcome will be the change in Montgomery-Asberg Depression Rating Scale (MADRS) from week 0 to +5 weeks.
Time Frame: 5 weeks
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The primary outcome will be the change in Montgomery-Asberg Depression Rating Scale (MADRS) from week 0 to +5 weeks.
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5 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Secondary outcomes related to mood will be the Montgomery-Asberg Depression Rating Scale (MADRS) measured at time +3, +5, +8, +16 and + 24 weeks relative to baseline.
Time Frame: up to 6 months
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Secondary outcomes related to mood will be the Montgomery-Asberg Depression Rating Scale (MADRS) measured at time randomisation, +3, +5, +8, +16 and + 24 weeks relative to baseline.
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up to 6 months
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Clinical Anxiety Scale (CAS)
Time Frame: up to 6 months
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up to 6 months
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Quality of life will be assessed using the self-completed EuroQol EQ-5D instrument (http://www.euroqol.org/). The EQ-5D will be completed at 0, +3, +5, +8, +16 and + 24, weeks.
Time Frame: up to 6 months
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Quality of life will be assessed using the self-completed EuroQol EQ-5D instrument (http://www.euroqol.org/).
The EQ-5D will be completed at 0, +3, +5, +8, +16 and + 24, weeks.
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up to 6 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Chair: Ian N Ferrier, MRCPsych, Newcastle University
- Principal Investigator: Richard H McAllister-Williams, FRCP, Newcastle University
- Principal Investigator: Stuart Watson, MRCPsych, Newcastle University
- Principal Investigator: Ian M Anderson, FRCPsych, Manchester University
- Principal Investigator: Allan O House, MRCPsych, Leeds University
- Study Director: Elaine M McColl, PhD, Newcastle University
- Principal Investigator: Heinz CR Grunze, BoardCertPsy, Newcastle University
- Principal Investigator: Peter M Haddad, MRCPsych, Manchester University
- Principal Investigator: Thomas A Hughes, MRCPsych, Leeds Partnerships Nhs Foundation Trust
- Principal Investigator: Adrian Lloyd, MRCPsych, Northumberland, Tyne and Wear NHS Trust
- Principal Investigator: Andrew M Blamire, BSc, PhD, Newcastle University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2011
Primary Completion (Actual)
February 1, 2013
Study Completion (Actual)
June 1, 2013
Study Registration Dates
First Submitted
June 17, 2011
First Submitted That Met QC Criteria
June 17, 2011
First Posted (Estimate)
June 20, 2011
Study Record Updates
Last Update Posted (Estimate)
July 17, 2014
Last Update Submitted That Met QC Criteria
July 16, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EME-08/43/39
- ISRCTN (Registry Identifier: ISRCTN11460478)
- 2009-015165-31 (EudraCT Number)
- EME Grant (Other Grant/Funding Number: 08/43/39)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Baylor College of MedicineUniversity of TexasRecruitingDepression | Depression Moderate | Depression Severe | Suicide and Self-harm | Depression in Adolescence | Depression MildUnited States
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University of Cape TownNational Institute of Mental Health (NIMH)CompletedPostpartum Depression | Clinical Depression | Moderate DepressionSouth Africa
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Washington University School of MedicinePatient-Centered Outcomes Research Institute; National Institute of Mental...CompletedMajor Depressive Disorder | Treatment Resistant Depression | Treatment-Refractory Depression | Late Life Depression | Geriatric DepressionUnited States, Canada
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Northern Illinois UniversityUniversity Autonoma de Santo DomingoTerminatedDepression Moderate | Depression MildUnited States, Dominican Republic
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Gerbera Therapeutics, Inc.Not yet recruitingPostpartum Depression | Depression, Postpartum | Postnatal Depression | Post-partum Depression | Post-Natal DepressionUnited States
Clinical Trials on Metyrapone
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Istituto Auxologico ItalianoHRA PharmaRecruiting
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Baker Heart Research InstituteUnknownObesity | Metabolic Syndrome | Insulin ResistanceAustralia
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National Center for Research Resources (NCRR)University of TexasUnknownBrain Injury | Craniocerebral TraumaUnited States
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Nationwide Children's HospitalCompletedAdrenal Insufficiency | Prader Willi SyndromeUnited States
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Universitätsklinikum Hamburg-EppendorfCompleted
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Mayo ClinicRecruitingAutonomous Cortisol Secretion | Mild Autonomous Cortisol Secretion (MACS)United States
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GlaxoSmithKlineCompletedDepressive Disorder and Anxiety DisordersUnited Kingdom
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Eleonora SeeligCompletedGlucocorticoid EffectSwitzerland
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Rose Research Center, LLCFoundation for a Smoke-Free World; Embera NeuroTherapeutics, Inc.RecruitingSmoking Cessation | Tobacco Use DisorderUnited States