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Trial registered on ANZCTR


Registration number
ACTRN12613000209796
Ethics application status
Approved
Date submitted
14/02/2013
Date registered
21/02/2013
Date last updated
31/03/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Effectiveness of psychostimulant and broader action antidepressant medications for patients with melancholic depression
Scientific title
Randomized controlled trial of methylphenidate (either as a monotherapy or an adjunct treatment) compared to an antidepressant group (dual action or tricyclic antidepressants) for patients with treatment-resistant melancholic depression to see if effective in improvement in depression ratings and remission over an 8-week period.
Secondary ID [1] 281889 0
Nil.
Universal Trial Number (UTN)
U1111-1139-2174
Trial acronym
TOMEDS_PS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melancholic Depression 288289 0
Condition category
Condition code
Mental Health 288632 288632 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The trial involves three treatment groups:
1. Methylphenidate (MPD) monotherapy (Group 1)
2. Antidepressant monotherapy (group 2)
3. MPD and antidepressant combination Group 3)

Administration of medication will be as follows for the three treatment groups:

Group 1: : MPD will be progressively titrated up from 10 mg (taken daily) and with the dose increase ceased if the subject reports (i) a full response or significant side-effects, or (ii) no improvement beyond that of previous dose increase, or (iii) mood worsens on dose increase. Maximum dose of 30 mg/day. The managing clinician will assess clinical progress, pulse rate and blood pressure on a fortnightly basis.

Group 2: Administration of a dual or broad-action antidepressant, with decision dictated by previous failed antidepressant drug classes. Subjects who have only trialed an selective serotonin reuptake inhibitor (SSRI) will be prescribed a dual action antidepressant (desvenlafaxine) while patients that have previously trialed a dual-action drug will be prescribed a tricyclic antidepressant (dothiepin). These medications will be administered and titrated in line with current clinical procedures and patients will be clinically reviewed fortnightly.

Group 3: As above, for MPD. Antidepressant will be selected in line with previous antidepressants trialed by patient and titrated in line with standard clinician practice.

MPD will be administered in tablet form (10mg tablets; Trade name: Ritalin) with approval for prescription sought from the Pharmaceutical Branch of NSW Health per standard clinical procedures.

The antidepressant dose will be administered in line with standard clinical procedure and on a case by case basis with (as for MPD) the dose increase ceased if the subject reports (i) a full response or significant side-effects, or (ii) no improvement beyond that of previous dose increase, or (iii) mood worsens on dose increase. Maximum dose administered in line with standard clinical guidelines.
Intervention code [1] 286452 0
Treatment: Drugs
Comparator / control treatment
Comparator group is the antidepressant monotherapy group, with the choice of antidepressant dictated by previous medications trialled and respective responses.
Control group
Active

Outcomes
Primary outcome [1] 288870 0
Improvement in depressive severity (via responder and remission rates) on the Quick Inventory of Depressive Symptomatology (QIDS). .


Timepoint [1] 288870 0
QIDS: Baseline, weekly for 8 weeks after commencing trial medication, follow-up (at 8 weeks after commencing trial medication).
Primary outcome [2] 288912 0
Depressive symptom severity will be assessed by the Hamilton Depression Inventory (HAM-D).

A trial ‘responder’ is operationalized as an improvement of 50% or more and a ‘remitter’ by having a Hamilton score of less than seven at the trial’s conclusion.
Timepoint [2] 288912 0
HAMD: Baseline, fortnightly for 8 weeks after commencing trial medication, follow-up (at 8 weeks after commencing trial medication).
Secondary outcome [1] 301204 0
i. Improvement on other psychiatric constructs, such as anxiety (measured by the Depression and Anxiety Scale), life satisfaction and enjoyment (Quality of Life Enjoyment & Satisfaction Questionnaire) , social and occupational functioning (Work Productivity and Impairment Questionnaire).
Timepoint [1] 301204 0
i. These additional psychiatric constructs are measured at baseline, fortnightly (for 8 weeks) and 8-week follow-up.
Secondary outcome [2] 301317 0
ii. Rapidity of response: measured by speed of response on the primary measures.
Timepoint [2] 301317 0
ii. Speed of response refers to improvement on QIDS measure (administered at baseline, weekly for 8 weeks, and 8-week follow-up).
Secondary outcome [3] 301318 0
iii. Tolerance and dependence rates in the MPD groups: as indicated by managing clinician responsible for the administration of the trial medication.
Timepoint [3] 301318 0
iii. Tolerance and dependence rates: from information provided to managing clinician (can be at any point in time over the trial)
Secondary outcome [4] 301319 0
iv. Side-effect and drop-out rates: measured by the Side-effects Profile Form which is a list of the most common side-effects associated with the trial medications and which is completed by the researcher and managing clinician. This form was developed for the purpose of this study.
Timepoint [4] 301319 0
iv. Side-effect and drop-out rates: drop out rates measured at trial's conclusion and side-effects measured at week 1 (after commencing trial medication) and continuing weekly until week 8 of treatment (follow-up).

Eligibility
Key inclusion criteria
Inclusion Criteria:
1. Aged 18-65 years
2. Diagnosis of a unipolar melancholic depression according to a Black Dog Institute psychiatrist and DSM IV-TR criteria (measured by MINI)
3. Currently depressed with depressive onset present for at least 4 weeks
4. Score on HAM-D equal to or greater than 14 and score on QIDS equal to or greater than 11 (i.e. moderately to severely depressed)
5. Failed two or more SSRI or dual action antidepressants (but never trialed a TCA or monoamine oxidase inhibitor (MAOI))
6. Willing to accept randomized assignment to one of the three treatment options.
7. Prepared to commit to fortnightly visits to the BDI and participate in weekly phone calls with the researcher who will complete the QIDS and monitor side effects.
8. Able to provide written informed consent.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
1. Under 18 years of age, or over 65.
2. Poor written and/or spoken English.
3. Pregnant or breastfeeding
4. Medical condition which contraindicates any trial treatment groups (e.g. epilepsy, cardiovascular condition, resting pulse rate above 80, blood pressure above 140/100).
5. Currently psychotic or acutely suicidal
6. Current drug or alcohol problems
7. Has previously trialed a psychostimulant or was a previous ‘user’ of psychostimulant.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Once a patient is deemed eligible for the study they will be assigned a study enrollment number that will be used on all study documents and a randomly allocated treatment group (via a blocked randomization, which is computer-generated).

Allocation is concealed from all subsequent raters (who are blind to treatment group of all patients) and this is ensured by using a sealed opaque envelope with the patients treatment group inside and which is only seen by the participant, the managing clinician and the study researcher.

An independent (and blinded) research assistant will be rating the key outcome measures.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A blocked randomization will be computer generated.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
NA.
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary analyses will be on an intention-to-treat (ITT) analysis. Secondary analyses on patients who complied with treatment are potentially informative and will be considered. For longitudinal outcomes, generalized linear mixed models will be preferred as they accommodate data that is missing at random. At individual time-points missing data will probably necessitate multiple imputation and such analyses will be examined under multiple approaches to examine for sensitivity to method.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2013
Actual
17/04/2013
Date of last participant enrolment
Anticipated
1/12/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
225
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 597 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 6345 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 286737 0
Government body
Name [1] 286737 0
National Health and Medical Research Council (NHMRC)
Country [1] 286737 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
The University of New South Wales
High St
Kensington, NSW 2052
Australia
Country
Australia
Secondary sponsor category [1] 285514 0
None
Name [1] 285514 0
Address [1] 285514 0
Country [1] 285514 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288812 0
Human Research Ethics Committee
Ethics committee address [1] 288812 0
Ethics Secretariat
UNSW Grants Management Office
Rupert Myers Building, Level 3, South Wing
The University of New South Wales
SYDNEY NSW 2052
Ethics committee country [1] 288812 0
Australia
Date submitted for ethics approval [1] 288812 0
Approval date [1] 288812 0
30/10/2012
Ethics approval number [1] 288812 0
HC12503

Summary
Brief summary
The primary aim of the study to evaluate the effectiveness of MPD as a monotherapy and adjunctive antidepressant treatment in patients with melancholic depression who have failed orthodox antidepressant options.

Key Hypotheses:
1. Those receiving MPD and an antidepressant will show superior responder and remission rates compared to those receiving an antidepressant only
2. Those receiving MPD monotherapy will show comparable remission and responder rates to those in Group 2 (a non-inferiority hypothesis).
3. Those receiving MPD will improve more rapidly than those on antidepressants only
4. Substantive side-effects and drop-out rates will be lowest for patients on MPD only.
Trial website
None at present.
Trial related presentations / publications
None at present.
Public notes
None.

Contacts
Principal investigator
Name 37602 0
Prof Gordon Parker
Address 37602 0
Black Dog Institute.
Hospital Rd. Prince of Wales Hospital.
Randwick
2031, NSW, Sydney.
Country 37602 0
Australia
Phone 37602 0
+61 2 9382 4372
Fax 37602 0
+61 2 9382 4343
Email 37602 0
[email protected]
Contact person for public queries
Name 37603 0
Rebecca Graham
Address 37603 0
Black Dog Institute.
Hospital Rd, Prince of Wales Hospital
Randwick
2031, NSW, Sydney.
Country 37603 0
Australia
Phone 37603 0
+61 2 93829253
Fax 37603 0
Email 37603 0
[email protected]
Contact person for scientific queries
Name 37604 0
Dusan Hadzi-Pavlovic
Address 37604 0
Black Dog Institute.
Hospital Rd, Prince of Wales Hospital
Randwick
2031, NSW, Sydney.
Country 37604 0
Australia
Phone 37604 0
+61 2 93823716
Fax 37604 0
Email 37604 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.