Effect of Probiotics "Psychobiotics" on Depression and Metabolic Syndrome in Saudi Arabia

NCT ID: NCT06765057

Last Updated: 2025-09-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-02

Study Completion Date

2027-01-30

Brief Summary

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The goal of this clinical trial is to assess the effect of commercial multi-strains psychobiotics supplementation as an ad-on therapy on depressive symptoms and metabolic syndrome components (HDL-C, FPG, TGs, WC, BP) in adult depressed patients with pre-metabolic syndrome and metabolic syndrome. The second goal is to explore the effect of commercial multi-strains psychobiotics supplementation on the anthropometric measurement (weight, body mass index (BMI)) in adult depressed patients with pre-metabolic syndrome and metabolic syndrome. The main questions they aim to answer are:

* Will commercial multi-strains psychobiotics supplementation help to ease depressive symptoms as an ad-on therapy in patients with pre-metabolic syndrome and metabolic syndrome?
* Will commercial multi-strains psychobiotics supplementation improve anthropometric measurements and metabolic syndrome components (WC, FPG, BP, TGs, HDL-C) in depressed patients? Researchers will compare psychobiotics to a placebo (a look-alike substance that contains no drug) to see if psychobiotics work to improve depression and metabolic syndrome components.

Participants will:

* Be examined for depression, anxiety, and metabolic syndrome components (waist circumference, diabetes, blood pressure, triglycerides, and high-density lipoprotein).
* Be asked to conduct laboratory tests to determine the inclusion and exclusion criteria.
* Be given probiotics/ placebo to consume every day for 3 months (12 weeks).
* Repeat the examination and laboratory tests to determine the results.
* Be followed up weekly for adverse events and to insure their compliance with the study instructions.
* Be followed up after 4 weeks as an end-visit and will conduct the examination and the laboratory blood tests.

Detailed Description

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Recently, the United Nations (UN) announced depression as the leading cause of disability worldwide. According to the World Health Organization (WHO), depression can increase the risk of suicide and death. Its prevalence increased globally since 2005 from 4.4% and reached 18.4% in 2015 accounting for about 322 million of the population. Based on the study of the Global Burden of Disease (GBD) from 195 countries around the world including Saudi Arabia, depression incidence increased from 172.27 million to 258.16 million from 1990 to 2017 most of whom is from major depressive disorder (MDD).

In addition, according to the Saudi National Mental Health Survey in 2016, 34% of Saudis were having psychiatric disorders and 80% of those with severe situations did not attempt any health care. Moreover, the prevalence of MDD among Saudis was 0.6% and it was one of the top-rated mental health cases in Saudi Arabia. Not only that but also, a cross-sectional study showed that the incidence of depression increased even more among Saudis during the pandemic of coronavirus disease-19 (COVID-19) to be 20.9%.

Depression is characterized by a persistent feeling of sadness, loss of interest, feeling of low self-esteem, loss of energy, decreased or increased appetite, trouble sleeping, and thoughts of suicide. Basically, depression is categorized into two main categories which are MDD and persistent depressive disorder (known as dysthymia). Depression can impair the quality of life and well-being. Unfortunately, it can also affect health negatively by causing comorbid diseases such as cancer, heart disease, inflammation, and neurological and metabolic disorders.

According to Al-Khatib et al (2022), one of the metabolic disorders associated with depression is metabolic syndrome (MetS). The International Diabetes Federation (IDF) defined the MetS as the occurrence of three or more symptoms of the following: central obesity with waist circumference (WC) for men ≥ 94 centimeters while for women ≥ 80 centimeters, increased fasting plasma glucose (FPG) ≥ 100 mg/dl, increased blood pressure (BP) to ≥ 130 /≥ 85 mmHg, increased triglycerides (TGs) to equal or above 150 mg/dl, reduced high-density lipoprotein cholesterol (HDL-C) for men to \< 40 mg/dl while for women \< 50 mg/dl. Yin et al., 2013 defined the pre-metabolic syndrome (Pre-MetS) as the occurrence of at least two components of MetS that do not reach the diagnostic of MetS. As a matter of fact, depression can lead to MetS and vice versa. About 30% of individuals with depression have MetS; meanwhile, about 41% of individuals with depression and MetS also have high levels of inflammation. Individuals with inflammation tend to have obesity and MetS. Thus, in 2007, it was proposed that the onset of depression with comorbid MetS is called "MetS type II" in which a combination of neuronal, psychological, and metabolic disorder happens. Furthermore, Gawlik-Kotelnicka and Strzelecki mentioned in their recent review the term "metabolic depression" to depict the relationship between depression, obesity, and MetS.

Recently, it has been suggested that gut microbiota modulation by a combination of probiotics and anti-depressant is an effective treatment. Since the bidirectional relationship between brain and gut health was confirmed, the accumulated body of evidence revealed that mental health is impacted by what is called the gut-brain axis (GBA) in which the gut microbiome can affect brain health through special microorganisms known as psychobiotics. Psychobiotics are special types of probiotics; they are specified to positively influence neurotransmitters, endocrinal hormones, and anti-inflammatory cytokines. They are a supporting therapy as an add-on therapy for mood disorders and depression with little or no side effects. To our knowledge, there are no clinical trials conducting in Saudi Arabia to investigate the impact of probiotics efficiency on depressive symptoms, anthropometric measurement, and MetS components in adult patients which is the aim of this experimental study.

Conditions

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Depression Anxiety Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The probiotic and the placebo are packed in plain white sachets, with the study acronym and shelf life printed on them. The sachets are packed in plain white boxes that are all equally labelled with the study title, instructions for use and investigator contact details. Each participant will receive 6 boxes of the same randomization number. The study team will be blinded to the contents of each box. The coordinating investigator of the study team will distribute the numbered boxes to the participants. The investigators have access to the randomization data in case it is necessary to unblind for a serious event. Sealed code break envelopes per participant (located at the investigational site in a restricted-access, fireproof, vault, accessible within 24 hours) will be used and in the event of a code break, the name of the code breaker, the signature, date and time will be recorded on the outside of the envelope. Unblinding will automatically lead to exclusion from the trial.

Study Groups

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Winclove's Ecologic® Barrier Probiotics

Patients in the interventional group will consume psychobiotics daily in addition to their antidepressant medication for 12 weeks. All patients will be instructed to take 1 sachet in the morning before breakfast, and 1 sachet at the end of the day before going to bed. The product is a multispecies probiotic formulation consisting of 9 selected probiotic strains by Winclove's Ecologic® Barrier, Amsterdam, The Netherlands. Each participant will receive 6 boxes of the probiotic supplement, each box contains 30 sachets of 3 grams (180 sachets in total). During the period of 12 weeks, each participant will consume 168 sachets. The probiotic supplement is a freeze-dried powder of probiotic mixture at a dose of 2,5 x 109 colony forming units (CFU) per gram. Since participants should consume 2 sachets/day, they will consume 6 grams in total which equals 1.5 × 10\^10 CFU.

Group Type EXPERIMENTAL

Winclove's Ecologic® Barrier Probiotics

Intervention Type DIETARY_SUPPLEMENT

The investigational product is a multispecies probiotic formulation consisting of 9 selected probiotic strains: the following bacterial strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19 and Lactococcus lactis W58.

Control

Patients in the control group will consume similar sachets that are identical in physical appearance. The placebo is composed of the carrier of the probiotic product, that is maize starch and maltodextrins but contains no bacteria.

Group Type PLACEBO_COMPARATOR

Winclove's Ecologic® Barrier Probiotics Placebo

Intervention Type DIETARY_SUPPLEMENT

The placebo is composed of the carrier of the probiotic product that are identical in physical appearance, it includes maize starch and maltodextrins but contains no bacteria.

Interventions

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Winclove's Ecologic® Barrier Probiotics

The investigational product is a multispecies probiotic formulation consisting of 9 selected probiotic strains: the following bacterial strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19 and Lactococcus lactis W58.

Intervention Type DIETARY_SUPPLEMENT

Winclove's Ecologic® Barrier Probiotics Placebo

The placebo is composed of the carrier of the probiotic product that are identical in physical appearance, it includes maize starch and maltodextrins but contains no bacteria.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Major Depression Disorder (MDD) patients on antidepressants for at least 4 weeks or more.
* MDD patients with pre-metabolic syndrome (at least 2 of the MetS components) and metabolic syndrome (at least 3 of the following components: central obesity with WC for men ≥ 94 centimeters while for women ≥ 80 centimeter, increased FPG ≥ 100 mg/dl, increased BP to ≥ 130 / ≥ 85 mmHg, increased TGs equal or above 150 mg / dl, increased HDL cholesterol for men to \< 40 mg / dl while for women \< 50 mg / dl) (IDF., 2006).
* MDD patients with other comorbid diseases such as anxiety.

Exclusion Criteria

* Patients using any other supplements to improve mood.
* Patients using pre/pro/symbiotics supplement or antibiotics during the last 3 weeks before the intervention.
* Patients with chronic diseases (cardiac, renal, or hepatic diseases)
* Patients with gastro intestinal diseases (Crohn's disease, ulcerative colitis).
* Patients with infectious diseases (HIV/AIDS).
* Cancer patients or those undergoing chemotherapy.
* Patients with food allergies such as gluten intolerance or lactose intolerance.
* Pregnant and breastfeeding women.
* Patients with modified antidepressant dose during interventional period or receiving psychotherapy during the intervention.
* Patients with thyroid disorder.
* Patients following a diet to lose weight during the intervention.
* Diabetic patients who are insulin-dependent.
* patients receiving injections or medications to lose weight (Ozempic, Mounjaro …etc) either 3 weeks before or during the intervention.
* Patients using plasma-lipid lowering drug for less than 1 month before the intervention.
* Patients with substance abuse including alcohol addiction.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roaa Ahmed Alkreadees

OTHER_GOV

Sponsor Role lead

Responsible Party

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Roaa Ahmed Alkreadees

Study coordinator and Co-author

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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King Saud University Medical City

Riyadh, Riyadh Region, Saudi Arabia

Site Status RECRUITING

Countries

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Saudi Arabia

Central Contacts

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Roaa A Alkreadees

Role: CONTACT

00966555527073

Facility Contacts

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Roaa A. Alkreadees, MS

Role: primary

966555527073

References

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Altwaijri YA, Al-Habeeb A, Al-Subaie AS, Bilal L, Al-Desouki M, Shahab MK, Hyder S, Sampson NA, King AJ, Kessler RC. Twelve-month prevalence and severity of mental disorders in the Saudi National Mental Health Survey. Int J Methods Psychiatr Res. 2020 Sep;29(3):e1831. doi: 10.1002/mpr.1831. Epub 2020 Aug 15.

Reference Type BACKGROUND
PMID: 33245602 (View on PubMed)

Al-Khatib Y, Akhtar MA, Kanawati MA, Mucheke R, Mahfouz M, Al-Nufoury M. Depression and Metabolic Syndrome: A Narrative Review. Cureus. 2022 Feb 12;14(2):e22153. doi: 10.7759/cureus.22153. eCollection 2022 Feb.

Reference Type BACKGROUND
PMID: 35308733 (View on PubMed)

AlHadi AN, Alarabi MA, AlMansoor KM. Mental health and its association with coping strategies and intolerance of uncertainty during the COVID-19 pandemic among the general population in Saudi Arabia: cross-sectional study. BMC Psychiatry. 2021 Jul 28;21(1):382. doi: 10.1186/s12888-021-03370-4.

Reference Type BACKGROUND
PMID: 34320930 (View on PubMed)

Gawlik-Kotelnicka O, Strzelecki D. Probiotics as a Treatment for "Metabolic Depression"? A Rationale for Future Studies. Pharmaceuticals (Basel). 2021 Apr 20;14(4):384. doi: 10.3390/ph14040384.

Reference Type BACKGROUND
PMID: 33924064 (View on PubMed)

Gold SM, Kohler-Forsberg O, Moss-Morris R, Mehnert A, Miranda JJ, Bullinger M, Steptoe A, Whooley MA, Otte C. Comorbid depression in medical diseases. Nat Rev Dis Primers. 2020 Aug 20;6(1):69. doi: 10.1038/s41572-020-0200-2.

Reference Type BACKGROUND
PMID: 32820163 (View on PubMed)

Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006 May;23(5):469-80. doi: 10.1111/j.1464-5491.2006.01858.x.

Reference Type BACKGROUND
PMID: 16681555 (View on PubMed)

Liu Q, He H, Yang J, Feng X, Zhao F, Lyu J. Changes in the global burden of depression from 1990 to 2017: Findings from the Global Burden of Disease study. J Psychiatr Res. 2020 Jul;126:134-140. doi: 10.1016/j.jpsychires.2019.08.002. Epub 2019 Aug 10.

Reference Type BACKGROUND
PMID: 31439359 (View on PubMed)

Park C, Brietzke E, Rosenblat JD, Musial N, Zuckerman H, Ragguett RM, Pan Z, Rong C, Fus D, McIntyre RS. Probiotics for the treatment of depressive symptoms: An anti-inflammatory mechanism? Brain Behav Immun. 2018 Oct;73:115-124. doi: 10.1016/j.bbi.2018.07.006. Epub 2018 Jul 18.

Reference Type BACKGROUND
PMID: 30009996 (View on PubMed)

Sharma R, Gupta D, Mehrotra R, Mago P. Psychobiotics: The Next-Generation Probiotics for the Brain. Curr Microbiol. 2021 Feb;78(2):449-463. doi: 10.1007/s00284-020-02289-5. Epub 2021 Jan 4.

Reference Type BACKGROUND
PMID: 33394083 (View on PubMed)

Vlainic JV, Suran J, Vlainic T, Vukorep AL. Probiotics as an Adjuvant Therapy in Major Depressive Disorder. Curr Neuropharmacol. 2016;14(8):952-958. doi: 10.2174/1570159x14666160526120928.

Reference Type BACKGROUND
PMID: 27226112 (View on PubMed)

Related Links

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https://news.un.org/en/story/2017/02/552062

UN health agency reports depression now 'leading cause of disability worldwide'

http://www.who.int/publications-detail-redirect/depression-global-health-estimates

Depression and Other Common Mental Disorders: Global Health Estimates

http://pubmed.ncbi.nlm.nih.gov/22672648/

Apolipoprotein B/apolipoprotein A1 ratio is a good predictive marker of metabolic syndrome and pre-metabolic syndrome in Chinese adolescent women with polycystic ovary syndrome

Other Identifiers

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E-23-7867

Identifier Type: -

Identifier Source: org_study_id

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