Molecular basis of depression disorder and influence of omega-3 fatty acid on clinical symptoms and biomarkers
| ISRCTN | ISRCTN81655012 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN81655012 |
| Protocol serial number | APVV-15-0063 |
| Sponsor | Comenius University |
| Funder | Slovak Research and Development Agency (Agentúra na Podporu Výskumu a Vývoja) |
- Submission date
- 10/10/2016
- Registration date
- 19/10/2016
- Last edited
- 28/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
Mood disorders in children and adolescents are a serious problem worldwide and are becoming more common in younger children. In recent years, research has been focused on the adjuvant therapy of depression (extra treatment to enhance the effects of the main treatment) to reduce the consumption of antidepressants, prolong remission (disease-free periods) and improve the outlook for these patients. The use of Omega-3 fatty acids as an adjuvant therapy is promising, with beneficial effects in the prevention and treatment of depression. This study aims to assess the effectiveness of omega-3 fatty acids-rich fish oil in the treatment of depression symptoms in children and adolescents treated for depression as well as to find out what effects this has on the body by looking at biochemical markers (substances).
Who can participate?
Children and adolescents aged 10 -18 years suffering from depression who are registered at the Department of Child Psychiatry of Comenius University and Child University Hospital in Bratislava.
What does the study involve?
Patients are randomly allocated to one of two groups. Those in the first group take 20 mL of omega-3 fish oil emulsion every day for 12 weeks in addition to their usual treatment, followed by 4 weeks of not taking the oil. Those in the second group take 20 mL of omega-6 sunflower oil emulsion every day for 12 weeks in addition to their usual treatment, followed by 4 weeks of not taking the oil. At the start of the study, every two weeks during the 12-week treatment period, and then at 16 weeks, participant have their symptoms of depression assessed and have blood and saliva samples taken to measure for chemical indicators of the effects the supplements are having on the body.
What are the possible benefits and risks of participating?
Participants who receive the omega-3 oil may benefit from a reduction of their depressive symptoms. There are no known risks involved with participating.
Where is the study run from?
1. Comenius University (Slovakia)
2. Comenius University and Child University Hospital (Slovakia)
Who is funding the study?
Slovak Research and Development Agency (Slovakia)
When is the study starting and how long is it expected to run for?
March 2013 to June 2020
Who is the main contact?
Professor Zdenka Durackova
zdenka.durackova@fmed.uniba.sk
Contact information
Scientific
Institute of Medical Chemistry
Biochemistry and Clinical Biochemistry
Faculty of Medicine
Comenius University
Bratislava
813 72
Slovakia
 ORCID ID |
0000-0001-6956-7038 |
|---|---|
| Phone | +421 1 59357 564 |
| zdenka.durackova@fmed.uniba.sk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Single-centre randomized double-blind comparator controlled interventional study |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Molecular bases of depressive disorders in children and adolescents, effect of omega-3 fatty acids, inflammation and oxidative stress |
| Study acronym | Depoxin |
| Study objectives | Current study hypothesis as of 05/12/2023: The current study aims to compare the efficacy of 12 weeks of administration of omega-3 fatty acids present in fish oil emulsion with a control oil emulsion (omega-6 fatty acids rich sunflower oil emulsion) alongside standard antidepressant treatment on depressive symptoms in children and adolescents (10 to 18 years old). The study will investigate: 1. Clinical parameters: CDI score 2. Biochemical parameters: Lipid profile, fatty acid composition in serum LDL- and HDL-subfractions of lipoproteins, markers of oxidative stress and inflammation in blood, steroidal hormones in saliva, metabolites of kynurenine and serotonin pathway 3. Biophysical parameters: Fluidity of erythrocyte membranes 4. The length of telomeres in the buccal cells Previous study hypothesis: The aim of the current study is to compare the efficacy of 12 weeks administration of omega-3 fatty acids present in fish oil emulsion with a control oil emulsion (omega-6 fatty acids rich sunflower oil emulsion) alongside standard antidepressant treatment on depressive symptoms in children and adolescents (8 to 18 years old). The study will investigate: 1. Clinical parameters: CDI score 2. Biochemical parameters: Lipid profile, fatty acid composition in serum LDL- and HDL-subfractions of lipoproteins, markers of oxidative stress and inflammation in blood, steroidal hormones in saliva 3. Biophysical parameters: Fluidity of erythrocyte membranes 4. The length of telomeres in the buccal cells |
| Ethics approval(s) |
Approved 20/03/2013, Ethics Committee of the National Institute of Children’s Diseases and the Faculty of Medicine, Comenius University Bratislava (Limbova 1, Bratislava, 833 40, Slovakia; +421 2 59371209, +421 2 59371927; detska.klinika@nudch.eu), ref: None available |
| Health condition(s) or problem(s) studied | Depressive disorder (F32) or mixed anxiety and depressive disorder (F41.2) |
| Intervention | Patients are allocated in a 1:1 ratio to the two arms (Om3 and Om6) according to a computer-generated random sequence using block randomisation with a block-size of four. The randomisation was performed by the independent statistician. Patients are enrolled and assigned sequentially to adjuvant interventions by the physician. The allocation sequence is not available to any member of the research team until the databases had been completed and locked. Intervention group: Participants receive 20ml of an omega-3 FA rich fish oil emulsion (Om3), which provides 2400 mg of total omega-3 FA; 1000 mg EPA and 750 mg DHA, EPA:DHA ratio = 1.33:1, for 12 weeks in addition to their standard antidepressant therapy, followed by a 4 week wash out period. Control group: Participants receive an identically looking comparator omega-6 sunflower oil emulsion containing min 2467 mg of omega-6 linoleic acid provided by Cultech Ltd, Port Talbot (UK) for 12 weeks in addition to their standard antidepressant therapy, followed by a 4 week wash out period. Clinical examinations take place at the beginning of the project (week 0), and every 2 weeks for 3 months (weeks 2, 4, 6, 8, 10, 12) and after following 4 week wash-out period, at week 16. Ratings aree made using the self rated scale Children's Depression Inventory (CDI). Biological samples (blood, urine, saliva) are taken at the week 0, 6, 12 and 16. |
| Intervention type | Supplement |
| Primary outcome measure(s) |
Clinical symptoms of depression are determined using Children's Depression Inventory score (CDI) at baseline, 2, 4, 6, 8, 10, 12 and 16 weeks. |
| Key secondary outcome measure(s) |
1. Basic biochemical marker levels (glucose, uric acid, lipid profile (total cholesterol, LDL-CH, HDL-CH, TAG), creatinine, CRP, liver enzymes ALT, AST) are measured by testing blood samples taken at baseline, at the week 6 and 12 of intervention and after wash-out period, at the week 16 |
| Completion date | 30/06/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 10 Years |
| Upper age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 60 |
| Total final enrolment | 58 |
| Key inclusion criteria | 1. Children and adolescents who met diagnostic criteria for depressive disorder or mixed anxiety and depressive disorder according to ICD 10 2. No signs of chronic somatic disease 3. Normal eating habits 4. Parents/guardians are willing to provide a signed informed consent 5. Children and adolescents are willing to provide blood, urine and saliva samples |
| Key exclusion criteria | 1. Chronic somatic diseases (endocrine, metabolic, autoimmune) 2. Dietary restrictions (vegetarians, lactose intolerance, celiac disease) 3. Psychotic disorders 4. Eating disorders 5. Addiction to psychoactive compounds 6. Personality disorders 7. Organic mental disorders 8. Pervasive developmental disorders |
| Date of first enrolment | 01/03/2014 |
| Date of final enrolment | 30/06/2019 |
Locations
Countries of recruitment
- Slovakia
Study participating centres
Limbová 1
Bratislava
833 40
Slovakia
Faculty of Medicine
Sasinkova 2
Bratislava
813 72
Slovakia
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from zdenka.durackova@fmed.uniba.sk and jana.trebaticka@fmed.uniba.sk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | Pilot study results | 05/07/2017 | Yes | No | |
| Results article | Association of depression symptoms with levels of omega-3 and omega-6 fatty acids in serum | 01/05/2020 | 18/03/2020 | Yes | No |
| Results article | Lipid profile results | 08/10/2020 | 22/10/2020 | Yes | No |
| Results article | results for levels of thromboxane, brain-derived neurotrophic factor, homocysteine and vitamin D | 27/03/2021 | 06/04/2021 | Yes | No |
| Results article | Changes in stress hormones and markers of oxidative stress | 10/08/2022 | 30/08/2022 | Yes | No |
| Results article | The kynurenine and serotonin pathway, neopterin and biopterin in depressed children and adolescents: an impact of omega-3 fatty acids, and association with markers related to depressive disorder. A randomized, blinded, prospective study | 13/02/2024 | 28/02/2024 | Yes | No |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
28/02/2024: Publication reference added.
05/12/2023: The following changes were made:
1. The study hypothesis was changed.
2. Contact information was updated for the ethics committee.
3. The Comenius University and Child University Hospital study participating centre was updated to the Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University.
4. Lower and upper age limits (numbers and units) were added and the plain English summary was updated to reflect this change.
04/12/2023: Publication reference added.
30/08/2022: Publication reference added.
06/04/2021: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
22/10/2020: Publication reference added.
18/03/2020: Publication reference added.
08/10/2018: Publication reference added.
22/01/18: The following changes were made:
1. The recruitment end date was changed from 31/12/2017 to 30/06/2019.
2. The overall trial end date was changed from 30/06/2019 to 30/06/2020.
3. The intention to publish date was changed from 31/12/2016 to 30/06/2021.
