Antiglucocorticoid Augmentation of antiDepressants in Depression (ADD)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Northumberland, Tyne and Wear NHS Foundation Trust.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
National Institute for Health Research, Efficacy and Mechanism Evaluation Programme
Information provided by:
Northumberland, Tyne and Wear NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01375920
First received: June 17, 2011
Last updated: NA
Last verified: April 2011
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Depression
Drug: Metyrapone
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Antiglucocorticoid Augmentation of antiDepressants in Depression

Resource links provided by NLM:


Further study details as provided by Northumberland, Tyne and Wear NHS Foundation Trust:

Primary Outcome Measures:
  • The primary outcome will be the change in Montgomery-Asberg Depression Rating Scale (MADRS) from week 0 to +5 weeks. [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
    The primary outcome will be the change in Montgomery-Asberg Depression Rating Scale (MADRS) from week 0 to +5 weeks.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Clinical Anxiety Scale (CAS) [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    Additonal secondary outcome measures of symptomatology include the Clinical Anxiety Scale (CAS), an observer rated scale of current anxiety, the Beck Depressive Inventory (BDI) and State Trait Anxiety Inventory (STAI), which are patient rated scales of depression and anxiety. Measurements will be taken at time +3, +5, +8, +16 and +24 weeks relative to baseline.

  • 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 190
Study Start Date: February 2011
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Metyrapone, daily medication
500 milligrams Metyrapone to be taken orally twice daily for 3 weeks.
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
Drug: placebo
a matched placebo will be administered to patients to take twice a day for 3 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Patient Inclusion Criteria:

  1. Depression Severity. Patient must have a Hamilton Depression Rating Scale (HDRS17) score of 18 or greater (rated using the GRID-HAMD), consistent with a moderate to severe episode. The stability of the patient's clinical state will also be confirmed with a 2-week baseline lead-in period (week-2 to 0). A repeat HDRS17 score at time 0 is required to be 18 or greater.
  2. Treatment refractoriness. This will be 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).
  3. Current antidepressant treatment. At trial entry, 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).
  4. Age. Patients will be included who are aged 18-65. For the mechanistic sub-studies the patients upper age limit is 55.
  5. Handedness. For patients taking part in the EEG and fMRI mechanistic studies only, they must be right handed as assessed using the Edinburgh Handedness Inventory (EHI).

Healthy Control Inclusion Criteria:

  1. Aged 18-55.
  2. Currently psychiatrically well, confirmed through SCID interview and with HDRS17 score of five or less and no current psychotropic medication.
  3. No past history of psychiatric illness, as revealed by SCID interview, or requiring any treatment (formal psychotherapy or psychotropic medication).
  4. No first degree family history of psychiatric illness.
  5. Right handed as using the EHI.

Patient Exclusion Criteria:

  1. Any other DSM IV Axis I disorder other than an anxiety disorder considered to be secondary to a primary diagnosis of depression, confirmed using the Structured Clinical Interview for DSM (SCID).
  2. Physical co-morbidity which would render the use of Metyrapone inappropriate, including untreated hypothyroidism, disorders of steroid production, cardiac failure, angina, myocardial infarction within the last 3 years or renal failure.
  3. Pregnancy, determined by history and, if indicated, urine pregnancy test.
  4. Mothers who are breastfeeding.
  5. Use of concomitant medication that would interfere, in a pharmacodynamic or pharmacokinetic manner, with Metyrapone.
  6. Dependence on alcohol or other drug in the past 12 months, and/or current harmful use of alcohol or other drug.
  7. Recently having taken part in another research study that could interfere with the results of this one.

Healthy Control Exclusion Criteria:

  1. Any physical ill health which would render the use of Metyrapone inappropriate, including untreated hypothyroidism, disorders of steroid production, cardiac failure, angina, myocardial infarction within the last 3 years or renal failure. NOTE: healthy controls are NOT treated with Metyrapone.
  2. Pregnancy, determined by history and, if indicated, urine pregnancy test.
  3. Mothers who are breastfeeding.
  4. Use of any medication that would interfere, in a pharmacodynamic or pharmacokinetic manner, with Metyrapone.
  5. Dependence on alcohol or other drug in the past 12 months, and/or current harmful use of alcohol or other drug.
  6. 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)].
  7. Recently having taken part in another research study that could interfere with the results of this one.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01375920

Contacts
Contact: Ian N Ferrier, BSc, MBChB, MRCP, MRCPsych, MD +44 (0)191 2563248 i.n.ferrier@ncl.ac.uk
Contact: Jane Barnes, RN, BA(Hons), MSc +44 (0)191 2227249 jane.barnes@ncl.ac.uk

Locations
United Kingdom
Stockton Affective Disorders Service Recruiting
Newcastle upon Tyne, Teesside, United Kingdom, TS17 6SD
Contact: Baxi NP Sinha, DNB, MD, DPM, MB BS    01642 352870    baxi.sinha@tewv.nhs.uk   
Contact: Kate Hughes       kate.hughes@durham.ac.uk   
Principal Investigator: Baxi NP Sinha, DNB, MD, DPM, MB BS         
Newcastle Magnetic Resonance Centre Recruiting
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE4 5PL
Contact: Andrew M Blamire, BSc, PhD    +44 (0)191 248 1150    a.m.blamire@ncl.ac.uk   
Principal Investigator: Andrew M Blamire, BSc, PhD         
Newcastle Community Mental Health Team Recruiting
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
Contact: Stuart Watson, MBBS, MRCPsych, MD    +44 (0)191 2824065    stuart.watson@ncl.ac.uk   
Principal Investigator: Stuart Watson, MBBS, MRCPsych, MD         
Regional Affective Disorders Service Recruiting
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
Contact: Richard H McAllister-Williams, BSc, MBChB, PhD, MD, FRCPsych    +44 (0)191 2820361    r.h.mcallister-williams@ncl.ac.uk   
Principal Investigator: Richard H McAllister-Williams, BSc, MBChB, PhD, MD, FRCPsych         
North Tyneside Community Mental Health Team Recruiting
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE28 7PD
Contact: Adrian Lloyd, MBBS, MRCPsych, MD    +44 (0)191 220 2203    a.j.lloyd@ncl.ac.uk   
Principal Investigator: Adrian Lloyd, MBBS, MRCPsych, MD         
Leeds Community Mental Health Team Recruiting
Leeds, United Kingdom, LS12 3QE
Contact: Thomas A Hughes    +44 (0)113 3055376    tom.hughes@Leedspft.nhs.uk   
Contact: Tanefa A Apekey, BSc, MPhil, PhD       t.apekey@leeds.ac.uk   
Principal Investigator: Thomas A Hughes, MBChB, MRCPsych, MD         
Affective Disorders Service Recruiting
Manchester, United Kingdom, M13 9PT
Contact: Ian M Anderson, BA, MBBS, MRCP, MD, FRCPsych    +44 (0)161 2757428    ian.anderson@manchester.ac.uk   
Contact: Kate Williams, BSc, MSc       kate.williams-4@manchester.ac.uk   
Principal Investigator: Ian M Anderson, BA, MBBS, MRCP, MD, FRCPsych         
Manchester Community Mental Health Team Recruiting
Manchester, United Kingdom, M30 0GT
Contact: Peter M Haddad    +44 (0)161 7876007    peterhaddad@doctors.org.uk   
Contact: Kate Williams, BSc, MSc       kate.williams-4@manchester.ac.uk   
Principal Investigator: Peter M Haddad, BSc, MBChB, MSc, MRCPsych, MD         
Manchester Magnetic Resonance Centre Recruiting
Manchester, United Kingdom
Contact: Ian M Anderson       ian.anderson@manchester.ac.uk   
Contact: Kate Williams, BSc, MSc       kate.williams-4@manchester.ac.uk   
Principal Investigator: Ian Anderson         
Northumberland, Tyne and Wear NHS Foundation Trust Recruiting
Newcastle upon Tyne, United Kingdom, NE3 3XT
Contact: Ian N Ferrier, BSc, MBChB, MRCP, MRCPsych, MD       i.n.ferrier@ncl.ac.uk   
Contact: Lucy H Stevens, BSc       l.stevens@ncl.ac.uk   
Sub-Investigator: Richard H McAllister-Williams, BSc, MBChB, PhD, MRCPsych, MD         
Sub-Investigator: Stuart Watson, MBBS, MRCPsych, MD         
Sub-Investigator: Heninz CR Grunze, Licensure as Phtsician, MD         
Sub-Investigator: Adrian J Lloyd, MBBS, MRCPsych, MD         
Principal Investigator: Ian N Ferrier, BSc, MBChB, MRCP, MRCPsych, MD         
Sponsors and Collaborators
Northumberland, Tyne and Wear NHS Foundation Trust
National Institute for Health Research, Efficacy and Mechanism Evaluation Programme
Investigators
Study Chair: Ian N Ferrier, BSc(Hons), MBChB, MRCP, MRCPsy Newcastle University
Principal Investigator: Richard H McAllister-Williams, BScHons, MBChB, PhD, MD, FRCP Newcastle University
Principal Investigator: Stuart Watson, MBBS, MRCPsych, MD Newcastle University
Principal Investigator: Ian M Anderson, BA, MBBS, MRCP, MD, FRCPsyc Manchester University
Principal Investigator: Allan O House, BSc, MBBS, MRCP, MRCPsych, DM Leeds University
Study Director: Elaine M McColl, BA(Hons), MSc, PhD Newcastle University
Study Director: Ian N Steen, BSc, MSc, PhD Newcastle University
Principal Investigator: Heinz CR Grunze, Licensure, DM, Board Cert Psyc Newcastle University
Principal Investigator: Peter M Haddad, BSc, MBChB,MSc,MRCPsych, MD Manchester University
Principal Investigator: Thomas A Hughes, MBChB, MRCPsych, MD Leeds Partnerships NHS Foundation Trust
Principal Investigator: Adrian Lloyd, MBBS, MRCPsych, MD Northumberland, Tyne and Wear NHS Trust
Principal Investigator: Andrew M Blamire, BSc, PhD Newcastle University
  More Information

Additional Information:
No publications provided

Responsible Party: Dr Ali Zaatar, Northumberland, Tyne and Wear NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01375920     History of Changes
Other Study ID Numbers: EME-08/43/39, ISRCTN, 2009-015165-31, EME Grant
Study First Received: June 17, 2011
Last Updated: June 17, 2011
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Northumberland, Tyne and Wear NHS Foundation Trust:
Depression
Antiglucocorticoid
Anti-depressants

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Metyrapone
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014