Antiglucocorticoid Augmentation of antiDepressants in Depression

NCT01375920 | Completed Phase 3 DMC

• 4 other identifiers: EME-08/43/39ISRCTN2009-015165-31EME Grant
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Depression

Keywords

Depression; Antiglucocorticoid; Anti-depressants

Outcome Measures

Primary Outcomes (1)

• The primary outcome will be the change in Montgomery-Asberg Depression Rating Scale (MADRS) from week 0 to +5 weeks.

  The primary outcome will be the change in Montgomery-Asberg Depression Rating Scale (MADRS) from week 0 to +5 weeks.

  5 weeks

Secondary Outcomes (3)

• 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.

  up to 6 months

• Clinical Anxiety Scale (CAS)

  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.

  up to 6 months

Study Arms (2)

Metyrapone, daily medication

ACTIVE COMPARATOR

500 milligrams Metyrapone to be taken orally twice daily for 3 weeks.

Drug: Metyrapone

placebo

PLACEBO COMPARATOR

a matched placebo will be given for patients to take twice daily

Drug: placebo

Interventions

Metyrapone DRUG

500 milligrams to be taken twice a day orally

Also known as: Metyrapone also known as Metopirone

Metyrapone, daily medication

placebo DRUG

a matched placebo will be administered to patients to take twice a day for 3 weeks

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Jane Barnes: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (11)

Stockton Affective Disorders Service

Newcastle upon Tyne, Teesside, TS17 6SD, United Kingdom

Location

Newcastle Community Mental Health Team

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

Location

Regional Affective Disorders Service

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

Location

North Tyneside Community Mental Health Team

Newcastle upon Tyne, Tyne and Wear, NE28 7PD, United Kingdom

Location

Newcastle Magnetic Resonance Centre

Newcastle upon Tyne, Tyne and Wear, NE4 5PL, United Kingdom

Location

Bradford District Care Trust

Bradford, United Kingdom

Location

Leeds Community Mental Health Team

Leeds, LS12 3QE, United Kingdom

Location

Affective Disorders Service

Manchester, M13 9PT, United Kingdom

Location

Manchester Community Mental Health Team

Manchester, M30 0GT, United Kingdom

Location

Manchester Magnetic Resonance Centre

Manchester, United Kingdom

Location

Northumberland, Tyne and Wear NHS Foundation Trust

Newcastle upon Tyne, NE3 3XT, United Kingdom

Location

MeSH Terms

Conditions

Depression

Interventions

Metyrapone

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ian N Ferrier, MRCPsych

  Newcastle University

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

• Elaine M McColl, PhD

  Newcastle University

  STUDY DIRECTOR

• Ian N Steen, PhD

  Newcastle University

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 17, 2011
• First Posted: June 20, 2011
• Study Start: February 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 17, 2014

Record last verified: 2014-07

Locations

GB (11)