Clinical trial NCT06765057: Effect of Probiotics "Psychobiotics" on Depression and Metabolic Syndrome in Saudi Arabia
Official title: Effect of Probiotics "Psychobiotics" on Depression in Adults With Obesity and Metabolic Syndrome in Riyadh City
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Depression Anxiety Disorder
Lead sponsor: King Saud Medical City
Sponsor class: OTHER_GOV
First posted: 2025-01-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 obese patients with 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 obese patients with 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 obesity and metabolic syndrome?
* Will commercial multi-strains psychobiotics supplementation improve anthropometric measurements and metabolic syndrome components (WC, FPG, BP, TGs, HDL-C) in obese 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 obesity comorbid with metabolic syndrome.

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.
* 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: 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. 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.

Eligibility criteria: Inclusion Criteria:

* Major Depression Disorder (MDD) patients on antidepressants for at least 4 weeks or more.
* MDD patients with obesity (BMI ≥ 30 kg/m2) 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 (irritable bowel syndrome, 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 started receiving psychotherapy during the intervention.
* Patients with thyroid disorder.
* Patients with anemia.
* Vegetarians.
* Patients following a diet to lose weight during.
* Diabetic patients.
* Patients using plasma-lipid lowering drug.
* Patients with substance abuse including alcohol addiction.

Primary outcomes:
measure: Psychological Assessment (depression1)
timeFrame: at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).
measure: Psychological Assessment (depression2)
timeFrame: at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).
measure: Psychological Assessment (Anxiety)
timeFrame: at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).
measure: Anthropometric Measurements
timeFrame: at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).
measure: Metabolic Syndrome Components (Waist circumference)
timeFrame: at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).
measure: Metabolic Syndrome Components (Medical Assessments/ Laboratory Tests)
timeFrame: at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).
measure: Metabolic Syndrome Components (Medical Assessments/ Blood Pressure)
timeFrame: at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
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citation: 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.
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