Antiglucocorticoid Augmentation of antiDepressants in Depression (ADD)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01375920 |
Recruitment Status :
Completed
First Posted : June 20, 2011
Last Update Posted : July 17, 2014
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Condition or disease | Intervention/treatment | Phase |
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Depression | Drug: Metyrapone Drug: placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 190 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Antiglucocorticoid Augmentation of antiDepressants in Depression |
Study Start Date : | February 2011 |
Actual Primary Completion Date : | February 2013 |
Actual Study Completion Date : | June 2013 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Metyrapone, daily medication
500 milligrams Metyrapone to be taken orally twice daily for 3 weeks.
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Drug: Metyrapone
500 milligrams to be taken twice a day orally
Other Name: Metyrapone also known as Metopirone |
Placebo Comparator: placebo
a matched placebo will be given for patients to take twice daily
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Drug: placebo
a matched placebo will be administered to patients to take twice a day for 3 weeks |
- The primary outcome will be the change in Montgomery-Asberg Depression Rating Scale (MADRS) from week 0 to +5 weeks. [ Time Frame: 5 weeks ]The primary outcome will be the change in Montgomery-Asberg Depression Rating Scale (MADRS) from week 0 to +5 weeks.
- 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 ]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.
- Clinical Anxiety Scale (CAS) [ Time Frame: up to 6 months ]
- Mood as measured by YMRS and BDI at time 0, +3, +5, +8, +16, +24 weeks
- Anxiety as measured by the CAS and STAI at time 0, +3, +5, +8, +16, +24 weeks
- Quality of life, assessed using the EQ-5D at weeks 0, +3, +5, +8, +16, +24
- Tolerability assessed using the TSES and self-report at weeks 0, +3, +5, +8 (additional self-report at weeks +1, +2 and +4)
- Suicide risk assessed at weeks 0, +1, +3, +5, +8, +16, +24
- Hypothalamic-Pituitary-Adrenal (HPA) axis function assessed by salivary cortisol awakening response (CAR) and sample at 11 pm at weeks 0, +3 and +5
- Safety assessments including blood pressure, urea and electrolytes and plasma cortisol levels at weeks -2, +1 and +5
- 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 ]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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01375920
United Kingdom | |
Stockton Affective Disorders Service | |
Newcastle upon Tyne, Teesside, United Kingdom, TS17 6SD | |
Newcastle Community Mental Health Team | |
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP | |
Regional Affective Disorders Service | |
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP | |
North Tyneside Community Mental Health Team | |
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE28 7PD | |
Newcastle Magnetic Resonance Centre | |
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE4 5PL | |
Bradford District Care Trust | |
Bradford, United Kingdom | |
Leeds Community Mental Health Team | |
Leeds, United Kingdom, LS12 3QE | |
Affective Disorders Service | |
Manchester, United Kingdom, M13 9PT | |
Manchester Community Mental Health Team | |
Manchester, United Kingdom, M30 0GT | |
Manchester Magnetic Resonance Centre | |
Manchester, United Kingdom | |
Northumberland, Tyne and Wear NHS Foundation Trust | |
Newcastle upon Tyne, United Kingdom, NE3 3XT |
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 | |
Study Director: | Ian N Steen, 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 |
Responsible Party: | Jane Barnes, Professor, Northumberland, Tyne and Wear NHS Foundation Trust |
ClinicalTrials.gov Identifier: | NCT01375920 |
Other Study ID Numbers: |
EME-08/43/39 ISRCTN ( Registry Identifier: ISRCTN: 45338259 ) 2009-015165-31 ( EudraCT Number ) EME Grant ( Other Grant/Funding Number: 08/43/39 ) |
First Posted: | June 20, 2011 Key Record Dates |
Last Update Posted: | July 17, 2014 |
Last Verified: | July 2014 |
Depression Antiglucocorticoid Anti-depressants |
Depression Depressive Disorder Behavioral Symptoms Mood Disorders Mental Disorders |
Metyrapone Antimetabolites Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors |