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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618000748213
Ethics application status
Approved
Date submitted
2/05/2018
Date registered
4/05/2018
Date last updated
6/09/2019
Date data sharing statement initially provided
6/09/2019
Date results information initially provided
6/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of saffron as an adjunct treatment for unremitted depression in adults
Scientific title
Efficacy of saffron as an adjunct treatment for unremitted depression in adults: a randomised, double-blind placebo-controlled study
Secondary ID [1] 294777 0
None
Universal Trial Number (UTN)
U1111-1213-2774
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 307688 0
Condition category
Condition code
Mental Health 306754 306754 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two tablets containing 14mg of a proprietary saffron extract (affron) (total daily dose of 28mg) will be consumed twice daily for 8 weeks by adults aged between 18 and 65 years. Participants will already be on a stable dose (at least 8 weeks) of a single pharmaceutical antidepressant but continues to suffer from mild-to-moderate depression. Adherence to capsule intake will be monitored through capsule return and count.
Intervention code [1] 301082 0
Treatment: Other
Comparator / control treatment
Placebo (containing microcellulose) is matched to the saffron tablets in terms of taste and appearance but does not contain any of the active ingredients.
Control group
Placebo

Outcomes
Primary outcome [1] 305743 0
Change in mood symptoms as assessed by – Montgomery–Åsberg Depression Rating Scale (Clinician-Rated) (MADRS)
Timepoint [1] 305743 0
Weeks 0, 4 and 8 (week 8 is primary endpoint)
Primary outcome [2] 305744 0
Change in mood symptoms as assessed by – Montgomery–Åsberg Depression Rating Scale (Self-Rated) (MADRS-S)
Timepoint [2] 305744 0
Weeks 0, 4 and 8 (week 8 is primary endpoint)
Secondary outcome [1] 346332 0
Change in quality of life and general health (composite secondary outcome) as assessed by the Short Form-36 Health Survey (SF-36).
Timepoint [1] 346332 0
Weeks 0, 4 and 8
Secondary outcome [2] 346333 0
Difference in adverse effects (e.g., constipation, diarrhoea, problems with sexual function, headache) as assessed by the Antidepressant Side-Effect Checklist (ASEC).
Timepoint [2] 346333 0
Weeks 0, 4 and 8

Eligibility
Key inclusion criteria
1. Adults (male and female) aged between 18 and 65 years
2. Currently taking a stable dose (at least 8 weeks) of a single pharmaceutical antidepressant (SSRI or SNRI)
3. Despite antidepressant treatment, continues to suffer from mild-to-moderate depression as assessed by a validated measure
4. Fluent in English
5. Willing to provide a personally signed and dated informed consent form detailing all pertinent aspects of the trial.
6. Willing and able to take prescribed placebo/saffron
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. DSM-5 diagnoses other than major depression, including but not limited to bipolar disorder, anxiety disorders, schizophrenia, psycho-organic syndromes, eating disorders, substance abuse or dependence disorders.
2. At significant risk of suicide or engaging in self-harm behaviours
3. Pregnant women, women who are breastfeeding or women who intended to fall pregnant.
4. Suffering from major medical illness, including neurodegenerative /neuroinflammatory disorders, such as Alzheimer’s disease, stroke, Parkinson’s disease or multiple sclerosis; autoimmune disorders, diabetes, inflammatory bowel disease, COPD, etc.
5. Currently taking medications including, but not limited to glucocorticoids, antibiotics, and anticoagulant medications. Use of analgesics (once a week) or contraceptive pills are permissible.
6. Currently taking saffron supplements and/or other specific herbal products, including omega-3 fatty acids.
7. Greater than 10-year history of depression

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)
Participants will be randomly allocated into placebo and treatment groups. These groups are named group 1 and group 2 and the primary investigator and participants will be unaware of which treatment these groups represent. Each participant will be allocated a participant number (1 to 160) based on the order of inclusion in the study. A computer-generated software will randomly assign the numbers 1 to 516 into either group 1 or 2.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Based on previous add-on studies we are predicting a moderate effect size of 0.4 to 0.5. Based on this, a total sample size of 100 to 150 is required. This gives an 80% chance of finding an effect at a statistical significance of 0.05. In this study, we will be recruiting 160 participants, which should give us the suitable power to find an effect, even after dropouts.

Pre and post analyses will be conducted to determine changes in the following:
1. Montgomery–Åsberg Depression Rating Scale (Clinician-Rated) (MADRS)
2. Montgomery–Åsberg Depression Rating Scale (Self-Rated) (MADRS-S)
3. Short Form-36 Health Survey (SF-36).
4. Antidepressant Side-Effect Checklist (ASEC).

Comparisons will be made between the two conditions to determine if changes in symptoms are significantly different.

These analyses will be conducted via a repeated measures analysis of variance via SPSS

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)
NSW,QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 299384 0
Commercial sector/Industry
Name [1] 299384 0
Pharmactive
Address [1] 299384 0
Avda.Severo Ochoa, 37 – Local 4J
28108. Alcobendas. Madrid. Spain
Country [1] 299384 0
Spain
Primary sponsor type
University
Name
Murdoch University
Address
90 South St, Murdoch WA 6150
Country
Australia
Secondary sponsor category [1] 298662 0
None
Name [1] 298662 0
Address [1] 298662 0
Country [1] 298662 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300285 0
Murdoch University Human Research Ethics Committee
Ethics committee address [1] 300285 0
90 South St
Murdoch WA 6150
Ethics committee country [1] 300285 0
Australia
Date submitted for ethics approval [1] 300285 0
08/02/2018
Approval date [1] 300285 0
26/03/2018
Ethics approval number [1] 300285 0
2018/011

Summary
Brief summary
In this randomised, double-blind, placebo-controlled study, 160 adults who are currently taking an antidepressant medication but continue to suffer from depressive symptoms (mild-to-moderate severity) will be randomly assigned to receive tablets containing either a saffron extract (28mg a day) or placebo for 8 weeks. Participants recruited for this study will be on a stable medication dose for at least 8-weeks and will have no plan to change the dosage or medication type during the study. We will assess change in depressive symptoms via a validated clinician-rated instrument and a self-report measure (to be completed every 4 weeks). We will also assess whether saffron is able to reduce some of the side effects associated with antidepressant drug use (in 2 studies it has previously shown to reduce sexually-related side effects).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83162 0
Prof Peter Drummond
Address 83162 0
Murdoch University, School of Psychology and Exercise Science, 90 South St Murdoch Western Australia 6150
Country 83162 0
Australia
Phone 83162 0
+61 8 9360 2415
Fax 83162 0
Email 83162 0
P.Drummond@murdoch.edu.au
Contact person for public queries
Name 83163 0
Dr Adrian Lopresti
Address 83163 0
Murdoch University, School of Psychology and Exercise Science, 90 South St Murdoch Western Australia 6150
Country 83163 0
Australia
Phone 83163 0
+61411969797
Fax 83163 0
Email 83163 0
a.lopresti@murdoch.edu.au
Contact person for scientific queries
Name 83164 0
Dr Adrian Lopresti
Address 83164 0
Murdoch University, School of Psychology and Exercise Science, 90 South St Murdoch Western Australia 6150
Country 83164 0
Australia
Phone 83164 0
+61411969797
Fax 83164 0
Email 83164 0
a.lopresti@murdoch.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
individual participant data underlying published results
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication
Available to whom?
case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
for IPD meta-analyses
How or where can data be obtained?
access subject to approvals by Principal Investigator
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 4002 0
Lopresti, AL, Smith, SJ, Hood, SD, & Drummond, PD. (2019) Efficacy of a standardised saffron extract (affron®) as an add-on to antidepressant medication for the treatment of persistent depressive symptoms in adults: A randomised, double-blind, placebo-controlled study, Journal of Psychopharmacology.
Attachments [1] 4002 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary