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Trial registered on ANZCTR


Registration number
ACTRN12613001067763
Ethics application status
Approved
Date submitted
20/09/2013
Date registered
24/09/2013
Date last updated
13/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Nutritional interventions for depression: An open label trial for nonresponders to probiotic treatment using a micronutrient formula.
Scientific title
The efficacy of a probiotic supplement in the treatment of depressive symptomatology in volunteers with moderate to very severe depression:
An open label trial using a micronutrient formula in non-responders.
Secondary ID [1] 283268 0
Nil
Universal Trial Number (UTN)
U1111-1148-2095
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 290141 0
Condition category
Condition code
Mental Health 290529 290529 0 0
Depression
Alternative and Complementary Medicine 290530 290530 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Open label trial using a micronutrient formula called Daily Essential Nutrients, made by Hardy Nutritionals. The key ingredients of this micronutrient formula include Vitamin A (as retinyl palmitate) 1920IU, Vitamin C (as ascorbic acid) 200mg, Vitamin D (as cholecalciferol) 1000IU, Vitamin E (as d-alpha tocopheryl succinate) 120IU, Vitamin K (as phylloquinone and menaquinone-7) 40mcg, Thiamin (as thiamin mononitrate) 20mg, Riboflavin 6mg, Niacin (as niacinamide) 30mg, Vitamin B6 (as pyridoxine hydrochloride) 23.3mcg, Folic acid (50% as L-methylfolate calcium) 500mcg, Vitamin B12 (as methylcobalamin) 300mcg, Biotin 360mcg, Pantothenic acid (as d-calcium pantothenate) 10mg, Calcium (as chelate) 440mg, Iron (as chelate) 4.6mg, Phosphorus (as chelate) 280mg, Iodine (from Pacific kelp) 68mcg, Magnesium (as chelate) 200mg, Zinc (as chelate) 16mg, Selenium (as chelate) 68mcg, Copper (as chelate) 2.4mg, Manganese (as chelate) 3.2mg, Chromium (as chelate) 208mcg, Molybdenum (as chelate) 48mcg, and Potassium (as chelate) 80mg. More detailed information, as well as a full ingredient list for the product, can be obtained from the manufacturer's website - http://www.hardynutritionals.com . The intervention requires the oral intake of 15 capsules per day (in 3 doses of 5, mid meal), for 8 weeks. Participants will be asked to record any doses missed as well as any unusual events in their life, in a study diary.
Intervention code [1] 287994 0
Treatment: Other
Comparator / control treatment
NA - This is an open label single group study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290555 0
MADRS score - Montgomery Asberg Depression Rating Scale - clinician
rated
Timepoint [1] 290555 0
Baseline, 8 weeks (end of trial)
Primary outcome [2] 290556 0
iCGI- Improved Clinical Global Improvement Scale - clinician-rated, severity and improvement
Timepoint [2] 290556 0
Baseline, 8 weeks
Primary outcome [3] 290557 0
QIDS - Quick Inventory of Depressive Symptomatology - patient-rated
Timepoint [3] 290557 0
Baseline, 4 weeks, 8 weeks (end of trial)
Secondary outcome [1] 304782 0
DASS - depression, anxiety and stress scale
Timepoint [1] 304782 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [2] 304783 0
DAS - Dysfunctional Attitude Scale
Timepoint [2] 304783 0
Baseline, 4 weeks, 8 weeks
Secondary outcome [3] 304784 0
ATQ - automatic thoughts questionnaire
Timepoint [3] 304784 0
Baseline, 4 weeks, 8 weeks

Eligibility
Key inclusion criteria
Must have been a participant in a previous study: An intervention using probiotics for depressive symptoms (Trial ID ACTRN12613000438752).

Must be a "non-responder" to the probiotic treatment after the open label phase. A response is classified as >50% change on MADRS (primary outcome measure).

Must have a MADRS score of >19 (moderate depression) at beginning of trial.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Identical to exclusion criteria for probiotic trial, as no new participants will be recruited (Trial ID ACTRN12613000438752).

Neurological disorder involving brain or other central function (e.g., epilepsy, MS, narcolepsy).

Any serious medical condition for which major medical interventions are anticipated during the duration of the trial.

Any patient known to be allergic to the ingredients of the intervention.

Pregnancy or breastfeeding.

Any other medication with primarily central nervous system activity, including mood stabilizers. Participants must have been off of these medications for a minimum of four weeks prior to the trial.

Patients will be excluded temporarily if they have taken an oral antibiotic in the previous 6 weeks. If an antibiotic is begun during the course of the trial, that patient will be withdrawn from the study.

Any subject judged clinically to be at serious risk for suicide or violence in the opinion of the researchers.

Participants will be asked to minimize their intake of colas, tea, coffee, alcohol, cigarettes and illicit drugs. These substances will be monitored as part of the trial.

Participants will be excluded if they take any antidepressant herbal supplement, including St John’s Wort and 5-HTP.

Renal, hepatic, cardiovascular and respiratory diseases

Any person whose immune system is known to be weakened (e.g. by HIV/AIDS, a genetic defect, long-term use of corticosteroids or taking immunosuppressive medications).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Upon completion of the probiotic intervention trial, non-responders to that intervention will be invited to participate in this trial with a new intervention. A new informed consent process will be undertaken and all participants who consent will all be given identical treatment (the micronutrient formula).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Analysis of the outcome measures will involve conducting a repeated measures ANOVA, comparing mean scores on outcome measures at baseline, 4 weeks and 8 weeks.

Proportion of responders will also be analysed - a response is defined as >50% change on the MADRS from baseline.

All analyses will be done on intent-to-treat basis - each patient who provides informed consent will be included in the analysis, regardless of compliance with treatment. If any patient drops out before the final eight week follow-up visit, the ‘last-observation-carried-forward’ technique will be used to impute the missing values. Complete documentation will be kept on non-completers, and their reasons for dropping out of the study prematurely.

The individual changes will be summarised with 95% confidence intervals derived from the r-ANOVA. A two-sided p-value <0.05 will be taken to indicate statistical significance.

The target sample size of 15 participants was determined from previous open label studies using micronutrients, whereby 15 participants was an adequate number to show significant change from pre to post measurements. Our experience with these micronutrients is that they usually have a large effect size, and so 15 is an adequate number to show change in preliminary, uncontrolled studies. However, the final number of participants will be dictated by the number of non-responders to probiotic treatment in the previous trial who choose to enter this new open label trial, so we may have more or less participants than our target.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/10/2013
Actual
1/11/2013
Date of last participant enrolment
Anticipated
30/05/2014
Actual
30/05/2014
Date of last data collection
Anticipated
Actual
1/08/2014
Sample size
Target
15
Accrual to date
Final
8
Recruitment outside Australia
Country [1] 5434 0
New Zealand
State/province [1] 5434 0
Canterbury

Funding & Sponsors
Funding source category [1] 288009 0
University
Name [1] 288009 0
University of Canterbury
Country [1] 288009 0
New Zealand
Primary sponsor type
Individual
Name
Julia Rucklidge
Address
University of Canterbury
Private Bag 4800
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 286730 0
University
Name [1] 286730 0
University of Canterbury
Address [1] 286730 0
Private Bag 4800
Christchurch 8140
Country [1] 286730 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289933 0
Southern HDEC
Ethics committee address [1] 289933 0
Ethics committee country [1] 289933 0
New Zealand
Date submitted for ethics approval [1] 289933 0
04/09/2013
Approval date [1] 289933 0
18/09/2013
Ethics approval number [1] 289933 0
URA/12/05/013

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43138 0
Mrs Amy Romijn
Address 43138 0
University of Canterbury
Private Bag 4800
Christchurch 8140
Country 43138 0
New Zealand
Phone 43138 0
6433642987ext 7705
Fax 43138 0
Email 43138 0
[email protected]
Contact person for public queries
Name 43139 0
Amy Romijn
Address 43139 0
University of Canterbury Private Bag 4800 Christchurch 8140
Country 43139 0
New Zealand
Phone 43139 0
6433642987ext 7705
Fax 43139 0
Email 43139 0
[email protected]
Contact person for scientific queries
Name 43140 0
Julia Rucklidge
Address 43140 0
University of Canterbury Private Bag 4800 Christchurch 8140
Country 43140 0
New Zealand
Phone 43140 0
+64 3 364 2987 ext. 7959
Fax 43140 0
Email 43140 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

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