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Trial record 2 of 2 for:    Effects of probiotics on symptoms of depression

Probiotics, Brain Structure and Psychological Variables (ProBrain01)

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ClinicalTrials.gov Identifier: NCT03478527
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : June 6, 2018
Sponsor:
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf

Brief Summary:

Theory and research on the gut-brain-axis emphasize complex interactions between the gut microbiota, immunological and hormonal responses, brain function, brain structure, as well as resulting behavioral manifestations, such as cognitive functions and mental illness. Probiotics are living micro-organisms that change the composition of the gut microbiota and hypothetically have a positive effect on the host's general health and well-being. Probiotic bacteria naturally occur in foods such as Sauerkraut, olives, and dark chocolate, and are currently also added to industrial products such as yogurt.

Regarding the effect of probiotics on brain structure and function, animal studies have shown that the administration of probiotics in mice and rats was linked to neurogenesis in the hippocampus and an improvement of associated cognitive functions. The majority of these studies applied probiotics for 4 weeks. The substances used in these studies were often composed of several bacterial strains, suggesting that the neurogenic effect may not be reducible to a specific type of probiotic bacteria.

Probiotics seem to be effective in improving memory abilities, including spatial and non-spatial memory, both in rodents and humans. Moreover, specifically regarding the beneficial effect of probiotics on anxiety, depression and stress, preliminary evidence in humans is compelling. However methodologically sound (randomized-controlled trial [RCT], 'blind') studies are still lacking.

To sum up, the present study is going to be the first RCT with human participants that investigates structural and functional changes of the hippocampus through probiotic bacteria, using Magnet Resonance Imaging (MRI). In addition, the study aims at advancing research in the field by investigating the effects of probiotics on a broad spectrum of cognitive functions, particularly those associated with hippocampal activity (e.g. spatial memory, verbal memory). Furthermore, effects on several types of mental illness (e.g. anxiety, depression, stress) will be studied. Potential translatory mechanisms that may promote the aforementioned effects will be examined, i.e. changes in immunological parameters, 'brain derived neurotrophic factor' (BDNF), and oxytocin.


Condition or disease Intervention/treatment Phase
Depressive Symptoms Anxiety Stress Dietary Supplement: Vivomixx® powder Other: Placebo powder Not Applicable

Detailed Description:

A double-blind RCT intervention study will be conducted to investigate the effect of a probiotic dietary supplement vs. a placebo, taken by healthy human participants (N = 60) for 28 consecutive days. Both substances are administered in doses of 4.4g (powder) per day.

The probiotic dietary supplement used in the present study is a freely available product (in powder form) sold under the name of Vivomixx®. Per 4.4g the powder contains 450 billion bacteria, composed of eight bacterial strains: Lactobacilli (L. paracasei, L. plantarum, L. acidophilus and L.delbrueckii subsp. bulgaricus), Bifidobacteria (B. longum, B. infantis, B. breve), and Streptococcus thermophiles.

This product was chosen, because a similar supplement with an identical composition of bacteria as Vivomixx® was found to be linked to hippocampal neurogenesis in mice. The placebo powder has a similar taste and consistency as the verum (Vivomixx®) powder, but contains no probiotic bacteria.

First, participants will be screened online for eligibility (T0). Before and after the 28-day intake period, participants are asked to perform several cognitive tests and fill out questionnaires (T1, T2) at our laboratory (ca. 2 - 2.5 hours). Afterwards, blood samples will be drawn (ca. 5 minutes) and a magnet resonance tomography (MRT) session (ca. 1 - 1.5 hours) will be conducted, where participants will perform an object pattern separation task in the scanner (T1, T2). Furthermore, a follow-up after 2 months (T3), including the same assessments as at T1 and T2, will be conducted.

During the intake period participants will fill out a brief questionnaire on a weekly basis, which includes an assessment of state depression and anxiety, defecation (control item to rule out adverse effects), recent (start of) intake of medication, recent (onset of) intake of antibiotics, and recent inter-current illness (e.g. influenza). In addition, participants will record their food intake (protocol) for one week (7 consecutive days) during the intake period.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

1 Verum group, receiving the probiotic Vivomixx® powder

1 Placebo group, receiving a placebo powder (similar taste and consistency as Vivomixx® powder)

Masking: Double (Participant, Investigator)
Masking Description: double blind
Primary Purpose: Basic Science
Official Title: Effects of Probiotic Bacteria on Brain Structure and Function and on Psychological Variables
Actual Study Start Date : January 8, 2018
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : May 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Experimental: verum condition probiotics
The verum condition probiotics in the present study is a freely available product, Vivomixx® powder (dietary supplement). Each dose (4.4g) contains 450 billion bacteria, composed of eight bacterial strains: Lactobacilli (L. paracasei, L. plantarum, L. acidophilus, L.delbrueckii subsp. bulgaricus), Bifidobacteria (B. longum, B. infantis, B. breve), and Streptococcus thermophiles. 30 Participants will be randomly assigned to this condition. The intake period is 28 days, daily dose = 4.4g.
Dietary Supplement: Vivomixx® powder
Participants will take in a daily dose of 4.4g for 28 consecutive days
Other Name: probiotic dietary supplement

Placebo Comparator: placebo condition
In the placebo condition participants will receive a placebo powder (comparable in taste and consistency to Vivomixx® = verum condition probiotics) that contains no probiotic bacteria. 30 Participants will be randomly assigned to that condition. The intake period is 28 days, daily dose = 4.4g.
Other: Placebo powder
Participants will take in a daily dose of 4.4g for 28 consecutive days




Primary Outcome Measures :
  1. Changes in hippocampal volume, assessed via Magnet Resonance Imaging (MRI) [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in hippocampal volume in verum experimental group (in comparison to placebo control)

  2. Changes in functional brain activation during fMRI task [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in functional connectivity (using BOLD signal) in hippocampal regions in verum experimental group (in comparison to placebo control) during pattern separation fMRI task

  3. Changes in depression [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in levels of depression, assessed with Beck's Depression Inventory - II Revised (BDI-II-R) sum score in verum experimental group (in comparison to placebo control)

  4. Changes in spatial navigation [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in test performance scores (number of correct responses, degree of accuracy measured as position hits) in the Tunnel task in verum experimental group (in comparison to placebo control)

  5. Changes in Interleukin-6 (IL-6) [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in IL-6 blood serum concentration levels in verum experimental group (in comparison to placebo control)

  6. Changes in IL-1ß [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in IL-1ß blood serum concentration levels in verum experimental group (in comparison to placebo control)

  7. Changes in Tumor Necrosis Factor alpha (TNF-alpha) [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in TNF-alpha blood serum concentration levels in verum experimental group (in comparison to placebo control)

  8. Changes in Brain Derived Neurotrophic Factor (BDNF) [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in blood serum level concentration of BDNF in verum experimental group (in comparison to placebo control)

  9. Changes in verbal learning test performance [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in verbal learning performance score, assessed with the Verbal Learning Memory Test (VLMT) in verum experimental group (in comparison to placebo control)

  10. Changes in pattern separation fMRI task [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in the pattern separation task performance (no. of correct responses to picture stimuli) in in verum experimental group (in comparison to placebo control)


Other Outcome Measures:
  1. Changes in Oxytocin (OXT) [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in blood serum concentration levels of OXT in verum experimental group (in comparison to placebo control)

  2. Changes in Processing speed or performance IQ [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in processing speed assessed by a digit-symbol test (BIS; Berliner Intelligenzskala) in verum experimental group (as compared to placebo control)

  3. Changes in cognitive emotion regulation - functional emotion regulation [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in functional emotion regulation questionnaire sum score (as assessed with the Cognitive Emotion Regulation Questionnaire; CERQ) in verum experimental group (as compared to placebo control)

  4. Changes in Sleepiness [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in sleepiness questionnaire sum score (ESS; Epworth Sleepiness Scale) scores in verum experimental group (as compared to placebo control)

  5. Changes in cognitive emotion regulation - dysfunctional emotion regulation [ Time Frame: at baseline (day 0) after intake period (day 28+) and at follow up (day 84+) ]
    changes in dysfunctional emotion regulation questionnaire sum score (as assessed with the Cognitive Emotion Regulation Questionnaire; CERQ) in verum experimental group (as compared to placebo control)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy participants
  • age 18-40
  • informed consent for all parts of the study (including MRT)
  • none of the exclusion criteria (see below) fulfilled

Exclusion Criteria:

  • age < 18 or > 40 years
  • pregnancy or breastfeeding
  • left-handedness
  • degenerative or inflammatory diseases of the central nervous system
  • severe cognitive/ neuropsychological impairment
  • severe pain syndrome or other severe organic diseases
  • epilepsy
  • (past or present) psychiatric disorders
  • neurological disorder
  • severe diabetic polyneuropathy
  • malignancies/ cancer
  • cardiac insufficiency
  • arterial hypertension
  • heart attack/ stroke
  • severe hepatic or renal insufficiency
  • diseases of the hemopoietic system
  • alcoholism/ drug addiction
  • medical history of severe allergic or toxic reactions
  • current participation in drug trial
  • doubts about legal capacity/ capability of understanding
  • referral to institutions based on court/ official order
  • treatment with centrally acting medication (e.g. antipsychotics, antiepileptics, antidepressants, etc.)
  • non-removable metal pieces (aneurysm clips, artificial limbs, etc.) or implanted electronic devices (pacemaker, osmotic or other implanted pumps, cochlear implants, etc.)
  • claustrophobia
  • acute (respiratory) infection, physical uneasiness
  • tattoos in the head region, permanent make-up
  • non-removable piercings
  • chronic/ acute gastrointestinal diseases
  • vegetarianism, veganism
  • current intake of antibiotics or intake of antibiotics at any time point during the last 2 months
  • lactose intolerance
  • general focus on probiotic diet

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03478527


Contacts
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Contact: Leonie Ascone Michelis, Dr. +49 152 51 93 84 24 l.ascone-michelis@uke.de

Locations
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Germany
Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Psychiatrie und Psychotherapie Recruiting
Hamburg, Germany, 20246
Contact: Jürgen Gallinat, Prof. Dr.    +49 (0) 40 7410 - 52205    j.gallinat@uke.de   
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
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Principal Investigator: Simone Kühn, Prof. Dr. Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Psychiatrie und Psychotherapie, UKE Martinistraße 52, 20246 Hamburg, Germany

Publications:

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Responsible Party: Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT03478527     History of Changes
Other Study ID Numbers: ProBrain01
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: June 6, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
Probiotics
Psychiatric Symptoms
Cognitive Function
Hippocampus
Oxytocin
Immunological Parameters

Additional relevant MeSH terms:
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Depression
Behavioral Symptoms