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Trial registered on ANZCTR


Registration number
ACTRN12613001299796
Ethics application status
Approved
Date submitted
5/09/2013
Date registered
22/11/2013
Date last updated
18/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Nutraceuticals as Monotherapy Treatments in Major Depressive Disorder: A Double-Blind, Randomised, Placebo-Controlled Trial
Scientific title
The Efficacy of S-Adenosyl Methionine (SAMe) and a Combination Nutraceutical as Monotherapy Treatments in Major Depressive Disorder: A Double-Blind, Randomised, Placebo-Controlled Trial
Secondary ID [1] 283141 0
NIL
Universal Trial Number (UTN)
U1111-1147-6091
Trial acronym
NMT-D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 289998 0
Condition category
Condition code
Mental Health 290382 290382 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants take 2 tablets and 2 capsules orally each day for 8 weeks in a 3-arm, double-blind, randomised, placebo-controlled trial.

Group A: SAMe (800mg/day) + cofactors folinic acid (500mcg/day) and vitamin B12 (200mcg/day);

Group B: Enhanced SAMe combination nutraceutical (CN) formulation consisting of SAMe (800mg/day), Omega-3 concentrate (EPA-esters 1000mg/day, DHA-esters 656mg/day), 5-HTP (200mg/day), zinc picolinate (30 mg/day) + cofactors folinic acid (500mcg/day), vitamin B12 (200mcg per day), vitamin B6 (200mg/day), vitamin E (40IU/day), vitamin C (60mg per day), and magnesium amino acid chelate (40mg per day).

Adherence will be monitored through tablet and capsule counts at fortnightly assessment sessions.
Intervention code [1] 287870 0
Treatment: Drugs
Comparator / control treatment
Group C: Placebo tablets and capsules, identical in appearance to the active treatments, made of microcrystalline cellulose (an inert plant product) and containing no active ingredients.
Control group
Placebo

Outcomes
Primary outcome [1] 290405 0
Severity of depressive symptoms measured with the Montgomery-Asberg Depression Rating Scale (MADRS)
Timepoint [1] 290405 0
Measured at baseline and weeks 2, 4, 6, and 8
Secondary outcome [1] 304434 0
Severity of self-reported depressive symptoms measured with the Beck Depression Inventory-II (BDI-II)
Timepoint [1] 304434 0
Measured at baseline and weeks 2, 4, 6, and 8
Secondary outcome [2] 304487 0
Health-related quality of life measured with the Short Form-12 (SF-12)
Timepoint [2] 304487 0
Measured at baseline and weeks 2, 4, 6, and 8
Secondary outcome [3] 304488 0
Symptom severity and global improvement measured with the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales
Timepoint [3] 304488 0
Measured at baseline and weeks 2, 4, 6, and 8
Secondary outcome [4] 304489 0
The CORE Assessment of Psychomotor Change
Timepoint [4] 304489 0
Measured at baseline and week 8
Secondary outcome [5] 304490 0
Anxiety measured with the Hamilton Anxiety Rating Scale (HAM-A)
Timepoint [5] 304490 0
Measured at baseline and weeks 2, 4, 6, and 8
Secondary outcome [6] 304491 0
Self-reported quality of sleep measured with the Leeds Sleep Evaluation Questionnaire (LSEQ)
Timepoint [6] 304491 0
Measured at baseline and weeks 2, 4, 6, and 8

Eligibility
Key inclusion criteria
Aged 18 to 70;
fluent in written and spoken English;
has the capacity to consent to the study and follow its procedures;
fulfills the DSM-IV-TR and DSM-5 diagnostic criteria for Major Depressive Disorder on structured interview (MINI-Plus);
presents with mild to moderate depression (MADRS 14-25) at time of study entry;
meets SAFER 2.0 criteria for a stable episode of depression.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Currently taking any antidepressant medication (SSRIs, SNRIs, tricyclics, MAOIs, mood stabilisers, etc);
current use of any nutraceutical including a multi-vitamin, omega-3, or psychotropic herbal medicine e.g. St John’s wort (a two week washout can occur before inclusion);
presents with suicidal ideation ( >1 on MADRS suicidal thoughts domain) at time of study entry;
three or more failed trials of pharmacotherapy or somatic therapy (e.g. ECT, TMS) for the current major depressive episode;
recently commenced psychotherapy (>4 weeks of stable treatment acceptable);
taking warfarin or phenytoin;
diagnosis of bipolar disorder I/II or schizophrenia on structured interview (MINI-Plus);
a primary clinical diagnosis of a substance/alcohol use disorder within the last 12 months on structured interview (MINI-Plus);
known or suspected clinically unstable systemic medical disorder (including cancer, organ failure, or serious cardio/cerebrovascular disease);
pregnancy or breastfeeding;
not using medically approved contraception (including abstinence) if female and of childbearing age;
allergy to seafood.

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)
Potential participants will be initially screened by phone to assess their suitability for the trial, then invited to meet the trial clinician at The Melbourne Clinic in Richmond or the Brisbane Royal and Women's Hospital in Herston for a baseline screening interview. During this interview, potential participants will receive detailed information about the study and will sign a consent form. A thorough screening interview will then take place, and those who meet inclusion criteria will be enrolled in the trial. Enrolled participants will be allocated a medication pack number, to which a treatment arm has already been randomly assigned by a disinterested third party. Trial clinicians will allocate packs sequentially. The colour, size, shape, and taste of the tablets and capsules, as well as their packaging, will be identical across treatment arms so as to conceal treatment allocation from participants and trial clinicians. The key linking the medication pack numbers with treatment arms will be maintained by the disinterested third party until data collection is completed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Medication pack number allocation to a treatment arm will be randomly assigned using permutated block randomisation by a disinterested third party. Trial clinicians will then allocate packs to enrolled participants sequentially.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
As this is a phase II pilot study, power calculations were not conducted to determine sample size. Analysis of data will be conducted with blinding to group allocations. The primary efficacy analysis will assess average treatment group differences for the primary outcome measure (MADRS) over the entire study period and use a likelihood based mixed-effects model, repeated measures approach (MMRM). Results from the analysis of dichotomous data (e.g. demographics and genetic data) will be presented as proportions (e.g. Relative Risks), with 95% confidence interval, and Fisher’s Exact p-value where appropriate. Non-parametric statistics will be used when assumptions for parametric methods are violated. Cohen’s d effect sizes will be calculated. All tests of treatment effects will be conducted using a two-sided alpha level of 0.05 and 95% confidence intervals. Data will be analysed using SPSS 22.0.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 1477 0
The Melbourne Clinic - Richmond
Recruitment hospital [2] 1478 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 7315 0
3121 - Richmond
Recruitment postcode(s) [2] 7316 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 287894 0
Government body
Name [1] 287894 0
National Health and Medical Research Council

Address [1] 287894 0
National Health and Medical Research Council GHD Building Level 1 16 Marcus Clarke St, Canberra 2600 ACT

Country [1] 287894 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Department of Psychiatry
The University of Melbourne
Victoria 3010
Country
Australia
Secondary sponsor category [1] 286623 0
None
Name [1] 286623 0
Address [1] 286623 0
Country [1] 286623 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289835 0
The Melbourne Clinic Research and Ethics Committee
Ethics committee address [1] 289835 0
The Melbourne Clinic
130 Church St, Richmond VIC 3121

Ethics committee country [1] 289835 0
Australia
Date submitted for ethics approval [1] 289835 0
Approval date [1] 289835 0
16/08/2013
Ethics approval number [1] 289835 0
TMCREC/232/13

Summary
Brief summary
The primary aim of this study is to investigate the efficacy and safety of SAMe versus a combination nutraceutical (SAMe + 5-HTP, EPA and zinc) in the monotherapy treatment of adults (n=60) with major depressive disorder in an 8-week, double-blind, randomised, placebo-controlled trial. The primary outcome measure is severity of depressive symptoms using the Montgomery-Asberg Depression Rating Scale (MADRS).
Trial website
nutrientsdepressionstudy.com
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42658 0
Dr Jerome Sarris
Address 42658 0
The Professorial Unit
The Melbourne Clinic
130 Church St, Richmond 3121 VIC

Country 42658 0
Australia
Phone 42658 0
61 3 9487 4748
Fax 42658 0
Email 42658 0
jerome.sarris@unimelb.edu.au
Contact person for public queries
Name 42659 0
Ms Jenifer Murphy
Address 42659 0
The Professorial Unit
The Melbourne Clinic
130 Church St, Richmond 3121 VIC
Country 42659 0
Australia
Phone 42659 0
61 3 9487 4748
Fax 42659 0
Email 42659 0
NAT-Dstudy@unimelb.edu.au
Contact person for scientific queries
Name 42660 0
Dr Jerome Sarris
Address 42660 0
The Professorial Unit
The Melbourne Clinic
130 Church St, Richmond 3121 VIC
Country 42660 0
Australia
Phone 42660 0
61 3 9487 4748
Fax 42660 0
Email 42660 0
jerome.sarris@unimelb.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary