Clinical trial NCT05964231: The Intervention of Psychobiotics in Patients With Anxiety Disorders
Official title: A Double-blind Randomized Controlled Trial Investigating Associations of Microbiota, Serum Total Antioxidant Capacity and Sleep or Psychiatric Symptoms Before and After the Intake of Psychobiotic Lactobacillus Paracasei
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anxiety Disorders
Keywords: anxiety
microbiota
psychobiotics
Lead sponsor: Mackay Memorial Hospital
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The investigators designed this double blind randomized controlled study and will recruit 120 patients 20 to 65 years old, with DSM-5 generalized anxiety disorder or unspecified anxiety disorder. After clinical symptoms and psychological evaluation and blood sampling, a semi-structural interview delivered by a psychiatrist will be established to confirm the DSM-5 diagnosis. The participants will be randomly assigned to the Lactobacillus paracasei PS23 psychotropic probiotic or placebo group. Blood and stool samples will be obtained after consent. The samples will be tested for biochemistry, inflammation index, cytokines, intestinal osmotic pressure, or gut permeability, and a Fitbit fitness watch will be given to measure changes in sleep.

Detailed description: This study aimed to recruit 120 subjects that meet the following inclusion criteria after the approval of the IRB. Those agreed to participate and signed the informed consent will be randomly divided into two groups of the Lactobacillus paracasei PS23 psychobiotics capsule and the placebo. Each group aims to recruit 60 people. The power analysis was conducted using effect size for outcomes of improvements in anxiety from previous studies. Based on a power of 80% and assuming a 30% dropout rate and an alpha level of 0.05, a sample of 120 participants (60 per group) will be required. All results will be analyzed using an intent-to-treat analysis based on treatment assignment, regardless of completion or not.

Eligibility criteria: Inclusion Criteria:

1. Age 20\~70 years old
2. Patients perceived that they had anxiety-related complaints, or with any type of anxiety disorders of adjustment disorders referred from the Departments of Psychiatry, Neurology, Internal Medicine, and Family Medicine in Mackay Memorial Hospital.
3. Adult GAD-7 ≥ 8 points (to screen for generalized anxiety disorder) or a DSM-5 diagnosis of generalized anxiety disorder (F41.1) or unspecified anxiety disorder (F41.9)
4. Those who are currently under the treatment of selective serotonin reuptake inhibitors (SSRI) will only be included if their SSRI treatment has been stable or has not been changed for 4 weeks.

Exclusion Criteria:

1. Have taken antibiotics or are receiving antibiotic treatment within one month.
2. Have used probiotic products in powder, capsule or tablet form within two weeks (excluding yogurt, Yakult and other related foods).
3. Patients who have undergone hepatobiliary gastrointestinal surgery (except for colorectal polypectomy and appendectomy).
4. Past or current patients with inflammatory bowel disease.
5. Those with a history of cancer.
6. Those who are allergic to lactic acid bacteria products.
7. Patients with severe depression (Patient Health Questionnaire-9 (PHQ-9) ≧ 20 points), or possible neurocognitive impairments (Mini-Mental States Examination (MMSE)\<20), or those that had suicidal ideation noted on item 9 from PHQ-9.
8. Patients with chronic psychiatric diseases who are currently taking drugs to treat acute diseases, organic brain diseases, or newly diagnosed or changed drugs within one month.
9. Those who are receiving parenteral nutrition.
10. Those who are evaluated by the principal investigator to be unsuitable to participate in the research.

Primary outcomes:
measure: Changes from the HAM-A compared to placebo.
timeFrame: change from baseline score at 8 weeks
Secondary outcomes:
measure: Differences in the Generalized Anxiety Disorder 7-item (GAD-7) compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Differences in the State and Trait Anxiety Index (STAI) compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Differences in Insomnia Severity index (ISI) compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Differences in The Quality of Life, Enjoyment, and Satisfaction Questionnaire-16 (QLESQ-16) compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Differences in the The Profile of Mood States (POMS) compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Differences in Visual Analogue Scale-GI (VAS-GI) compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Changes in blood TAC (Total Antioxidant Capacity) before and after consumption of probiotics
timeFrame: change from baseline score at 8 weeks
measure: Changes in blood DHEA-S (Dehydroepiandrosterone sulfate) compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Changes in blood Cortisol compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Changes in blood High sensitivity CRP (hs CRP) compared to placebo.
timeFrame: change from baseline score at 8 weeks
measure: Improvements and differences compared to placebo on oxidative, inflammation, and stress biomarkers.
timeFrame: change from baseline score at 8 weeks
measure: Changes zonulin and calprotectin in fecal sample compared to placebo.
timeFrame: change from baseline score at 8 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
Study officials:
affiliation: Mackay Memorial Hospital
name: Shu-I Wu, PhD
role: PRINCIPAL_INVESTIGATOR
References: