An interventional study of High-EPA multinutrient supplement. and Placebo in Anxiety and Depression, sponsored by University of Roehampton. Recruiting at 1 site in United Kingdom. Open to participants aged 18 Years to 29 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-06-01.
Sponsored by University of Roehampton · Not applicable, Interventional, and Prevention
This is a 12-week-long, randomised, double-blind, placebo-controlled trial exploring the efficacy of a high-EPA multinutrient supplement in the management of sub-clinical anxiety and depression. The investigators focus on young and healthy, adult university students, who may otherwise not be eligible for pharmacological or cognitive behavioural therapy interventions.
First-line treatment for anxiety disorders comprises Cognitive Behavioural Therapy, which is ineffective in a considerable minority of individuals, and pharmacological treatments, which often confer significant side effects. On the other hand, fish-oil-based supplements have been shown to be safer, efficacious alternatives, especially for individuals not eligible for behavioural or pharmacological therapies. Evidence from randomised controlled trials (RCTs) suggests that the long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may exert beneficial anxiolytic effects. It is also suggested that dietary components such as vitamins and minerals e.g. a-tocopherol (vitamin E) and Magnesium (Mg), may also play a role in mood. It is furthermore theorised that minor allelic carriage of desaturase and apolipoprotein E (APOE) polymorphisms may also influence the putative anxiolytic potential of dietary components. However, despite the abundance of findings in RCTs and animal studies, the putative synergism, additive effects and precise mechanism of action of these macro- and micronutrients on anxiety in humans are largely unknown. Furthermore, the evidence suggests that in depressive states, glutamate homeostasis is dysregulated in frontal brain regions, and in bipolar patients, glutamate concentration is increased in the anterior cingulate cortex. Supplementation with EPA-rich regimes for 12 weeks confers beneficial changes in glutamate concentrations and improvement in functional connectivity between brain regions associated with mood and improvement in global symptoms.
The investigators have designed a randomised, double-blind, placebo-controlled trial to explore the above. Students from the University of Roehampton, aged 18-29 years (Emerging Adulthood), are randomised on a 1:1 allocation ratio, in two groups, for 12 weeks:
Brain hemodynamic and neurochemical changes in response to supplementation with the EPA-rich regime are explored in a subgroup of volunteers by magnetic resonance imaging (MRI). Analyses take place at the Combined Universities Brain Imaging Centre (CUBIC), Royal Holloway, University of London and comprise:
The choice of the population was made on the basis of its high-risk nature; university students in Emerging Adulthood (18-29 years of age) experience persistent levels of high-academic stress, social disconnection and sleep disruption which increase anxiety levels and exacerbate psychological distress and disengagement from study. University students are thus a high-risk, vulnerable group characterised by higher and increasing rates of anxiety disorders compared to the general population. Furthermore, this population is largely neglected by the therapeutic literature.
The study hypothesis is that:
The investigators will perform mixed-model analysis of covariance for the study primary and secondary endpoints, on an intention-to-treat (ITT) and per-protocol (PP) basis. The investigation which will take place at the Department of Life Sciences of the University of Roehampton and the Combined Universities Brain Imaging Centre (CUBIC), Royal Holloway, University of London, harmonised with local and national guidelines and risk assessments, the code of Good Clinical Practice and the Declaration of Helsinki. The study findings will be reported in accordance with the CONSORT statement.
8,577 studies on the registry are indexed under Depression; 1,720 are open to participants now.
This study's planned enrollment of 94 is above the median of 81 across 7,063 interventional studies indexed under Depression.
Browse Depression studies →University of Roehampton is the lead sponsor of 24 studies on the registry; 5 are open to participants now.
Compared within Depression, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Anxiety Disorders. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
High-EPA multinutrient supplement.
Dietary Supplement: High-EPA multinutrient supplement.
Inert oil mix.
Other: Placebo
Three capsules with the largest meal of the day providing: * 1,125 mg EPA * 441 mg DHA * 330 mg Magnesium * 7.5 mg a-tocopherol
Also known as: Libretto
Three capsules with the largest meal of the day providing: * 3,060 mg sunflower seed oil * 60 mg lecithin * 300 mg glyceryl monostearate * 465 mg EPA/DHA (18%/12% respectively for blinding)
Change from Baseline in Anxiety on the 21-point Generalised Anxiety Disorder Assessment (GAD-7) at Week 12.
GAD-7 is a 7-item, validated, self-reported instrument used to screen for generalised anxiety disorder and to assess its severity over the past two weeks. Possible scores range from 0 (none) to 21 (severe).
Time frame: Baseline and Week 12.
Change from Baseline in Depression on the 24-point Patient Health Questionnaire (PHQ-8) at Week 12.
PHQ-8 is an 8-item, validated, self-reported instrument used as a diagnostic and severity measure for depressive disorders. Possible scores range from 0 (none) to 24 (severe).
Time frame: Baseline and Week 12.
Change from Baseline in Depression, Anxiety and Stress on the 21-item Depression, Anxiety and Stress Scale (DASS-21) at week 12.
DASS-21 is a validated tool comprising three self-report scales designed to measure the emotional states of depression, anxiety and stress.
Time frame: Baseline and Week 12.
Change from Baseline in the Proportion of Trials Selected as Happy Compared to the Alternative Emotion, Adjusted to a Scale of 0 to 15 on the Emotional Bias Task (EBT) at Week 12.
EBT is a 4-minute-long, computer-based test that detects perceptual bias in facial emotion perception. The key outcome measure for the EBT is the bias point; the proportion of trials selected as happy compared to the alternative emotion, adjusted to a scale of 0 to 15. This is used to determine the extent and direction of the participant's bias. Additionally, latency measures and measures of how many times each emotion was selected are also available.
Time frame: Baseline and Week 12.
Change from Baseline in Measures of Sustained Attention on the Rapid Visual Information Processing (RVP) at Week 12.
RVP is a 7-minute-long, computer-based test measuring sustained attention. Outcome measures cover latency (speed of response), probability of false alarms and sensitivity.
Time frame: Baseline and Week 12.
Change from Baseline in Measures of Retention and Manipulation of Visuospatial Information on Spatial Working Memory (SWM) at Week 12.
SWM is a 4-minute-long, computer-based test that measures strategy and working memory errors as a measure of retention and manipulation of visuospatial information. Outcome measures include errors (selecting boxes that have already been found to be empty and revisiting boxes which have already been found to contain a token) and strategy.
Time frame: Baseline and Week 12.
Change from Baseline in Measures of Response Inhibition on Stop Signal Task (SST) at Week 12.
SST is an up-to 14-minute-long, computer based test that measures response inhibition (impulse control). Outcome measures cover direction errors, proportion of successful stops, reaction time on Go trials, and stop signal reaction time (SSRT).
Time frame: Baseline and Week 12.
Change from Baseline in Dietary Protein on 24-hour Dietary Intake Recall at Week 12.
Intake24 will be used to capture 3 x 24-hour dietary intake recalls at baseline and endpoint to assess changes in dietary protein measured in grams (g). This is a validated web-based 24-hour dietary assessment tool for measuring dietary intake.
Time frame: Baseline and Week 12.
Change from Baseline in Dietary Energy on 24-hour Dietary Intake Recall at Week 12.
Intake24 will be used to capture 3 x 24-hour dietary intake recalls at baseline and endpoint to assess changes in dietary energy measured in kilocalories (kcal). This is a validated web-based 24-hour dietary assessment tool for measuring dietary intake.
Time frame: Baseline and Week 12.
Apolipoprotein E (APOE) and Fatty Acid Desaturase (FADS) Genotypes.
ApoE and FADs genotypes will be measured.
Time frame: Baseline.
Change from Baseline in Dietary Long-Chain Omega-3 Polyunsaturated Fatty Acids (LCn-3 PUFA) Intake at Week 12.
LCn-3 PUFA dietary intake changes will be assessed with a validated food frequency questionnaire (FFQ).
Time frame: Baseline and Week 12.
Change from Baseline in Whole Blood Fatty Acid Profile at Week 12.
Whole fatty acid composition will be measured.
Time frame: Baseline and Week 12.
Change from Baseline in Glutamate Concentrations in the Right and Left Ventrolateral Prefrontal Cortex and the Anterior Cingulate Cortex at Week 12.
Proton Magnetic resonance spectroscopy will be used to assess neurochemical changes in response to supplementation.
Time frame: Baseline and Week 12.
Change from Baseline in Seed-to-Voxel Functional Connectivity using Bilateral Orbitofrontal Cortex and Amygdala Seeds at Week 12.
Functional magnetic resonance imaging will be used to assess changes in functional connectivity in response to supplementation.
Time frame: Baseline and Week 12.
Plan to share: Yes — Data will be: Fully anonymised Stored for 8 years as per University of Roehampton's Research Ethics Committee guidelines and Code of Practice. Appended to the final published report as supplemental material. Available from the corresponding author upon request. Handled, processed, stored and destroyed as per Data Protection Act (2018). Collected in Microsoft Excel worksheets in one file per type of experiment including original and normalised values; images/graphs will be stored as .tiff or .jpg files. Held encrypted on password-protected, university-owned drives. Accessible only by the investigators. Submitted for publication within one year. Deposited in a public preprint server (e.g. bioRxiv). Additional files with legends explaining how the data has been saved and described will be prepared to allow replicability. All anonymised data volumes are expected to be small. Long-term backup/archiving will utilise secure in-house facilities and cloud-based storage.
Supporting information: Study protocol, Statistical analysis plan
Time frame: The data will become available upon publication of the study report and will remain available for eight years in accordance with the University of Roehampton's Research Ethics Code of Practice.
Access criteria: Fully anonymised data will be available from the corresponding author upon request.
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