Clinical trial NCT03495375: Treating Impulsivity in Adults With Probiotics
Official title: Randomized Placebo-controlled Treatment of Impulsivity in Adults With Probiotics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Impulsive Behavior
Compulsive Disorder
ADHD
Borderline Personality Disorder
Keywords: Impulsivity
Compulsivity
Aggression
Microbiome
Probiotic
Nutrition
Psychiatric disorders
Synbiotic2000Forte
Lead sponsor: Hospital Vall d'Hebron
Sponsor class: OTHER
Collaborators: name: Goethe University
name: Semmelweis University
name: University Medical Center Nijmegen
First posted: 2018-04-12
Enrollment: 180
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: A multicentre randomized double-blind placebo controlled parallel design (10 weeks) study investigating probiotic supplementation in highly impulsive adults (18-65 yrs; N=180). The probiotic studied is Synbiotic2000Forte that contain three well-studied anti-inflammatory lactic acid bacteria (LABs) and four fermentable fibers: Pediococcus pentosaceus 5-33:3, Lactobacillus paracasei subsp paracasei 19, and Lactobacillus plantarum 2362 in combination with the following four fermentable fibres: betaglucan, inulin, pectin and resistant starch. With this study we aim to detect, whether treatment with probiotics is effective in adults with high levels of impulsivity, compulsivity, and aggression.

Detailed description: Impulsivity is a cross-disorder trait relevant in several psychiatric disorders, e.g. Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD). They place a significant burden on patients, families and society in general. Only adults (aged 18 - 65 years) with a diagnosis of ADHD and/or BPD will be included in this study. We will also try to include at least 30% female participants to gender-balance the study.

Recruitment and treatment of participants will be provided at three trial centres: Vall d'Hebron Research Institute (VHIR), Goethe University Frankfurt (GU), Semmelweis University (SU), each enrolling 60 participants. Randomization to receive either Synbiotic2000Forte or placebo will be performed when signed informed assent by the participant has been obtained, eligibility checks have been conducted and at baseline assessment. An independent randomization service (www.randomization.com) will be used to ensure reliability and credibility in the randomization process. The study is double-blinded; neither the participants nor the clinicians involved in the study will have access to the randomization list.

In this placebo-controlled 10-week, we will evaluate a probiotic formula for oral administration called Synbiotic2000Forte (SF). Participants will take the probiotic once daily in the form of a powder that can be spread on top of cold foods such as muesli, salad, or yoghurt. Placebo will be a non-digestable carbohydrate with similar texture and flavor to the SF. Participants will be assessed at baseline before treatment is started (baseline demographics and primary- and secondary outcome measures will be collected and then monitored every five weeks for a total of 5 visits.

Proper conduct of data collection in the trial will be monitored by on-site visits of a monitoring staff throughout the study, and quality of data collected will further be monitored regularly by a statistical supervision team. Questionnaire data will be collected through Castor. All information collected in this study will remain strictly confidential. Data of participants will be coded in such a way that participants cannot be identified from the corresponding data according to the regulations (unique pseudocode identifier).

This study will be conducted according to the principles of the Declaration of Helsinki, version of 2008 and in accordance with the Medical Research Involving Human Subjects Act (WMO, as well as according to the ICH GCP Guideline E6 (1996), EU Directive 2001/20/EC and applicable regulatory requirements and guidelines in the participating countries/regions. Before the first subject has been enrolled in the trial, all ethical and legal requirements were met.

Eligibility criteria: Inclusion Criteria:

* Adults with a high level of impulsivity (with or without ADHD) based on a CGI-S-score ≥ 4.
* An Affective Reactivity Index (ARI) score ≥5 indicating a high level of multi dimensional impulsivity.
* Research diagnosis of attention-deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder (BPD) confirmed by structured diagnostic interview according to DSM-5 (ADHD: Diagnostic Interview for Adult ADHD (DIVA 2.0); BPD: Structured Clinical Interview for DSM-IV (SCID-II)).
* Not currently taking any antibiotics or probiotics.
* Deemed reliable and compliant with the protocol by the investigator.
* Ability to speak and comprehend the native language of the country in which the assessments take place.

Exclusion Criteria:

* Subject is being treated with a concomitant medication which is prohibited within this study according to the list of prohibited medications.
* Patients must be on stable medication (i.e. current dose is given since more than 30 days): up-titration is not allowed and careful clinical screening is done at all visits to check whether lower dosage is needed due to increased side effects as a result of treatment with Synbiotic2000Forte.
* Presence of major psychiatric disorders with psychotic's symptoms.
* Neurological disorder involving brain or other central function (e.g., intellectual disability with an assessed IQ \< 70, epilepsy, MS, narcolepsy) or other major psychiatric condition requiring hospitalization (e.g., significant mood disorder or psychosis).
* Major physical illness of the cardiovascular, endocrine, pulmonal, or the gastrointestinal system.
* History of or present clinically relevant somatic acute or chronic disorder that, in the opinion of the investigator, might confound the results of tolerability/safety assessment, or prohibit the patients from completing the study, or would not be in the best interest of the patient.
* Subject has a documented allergy, hypersensitivity, or intolerance to any of the ingredients of the intervention.
* Subject has taken another investigational product or taken part in a clinical study within 30 days prior to entering the study.

Primary outcomes:
measure: Change in the self-rating of affective reactivity (ARI-S)
timeFrame: Assessed at Baseline, at week 5, week 10 and week 11.
measure: Clinical Global Impression - Improvement (CGI-I) total score of 1 or 2 (much improved, very much improved).
timeFrame: assessed at weeks 5, 10, and 11.
Secondary outcomes:
measure: Change in Clinical Global Impression - Severity (CGI-S)
timeFrame: Screnning assessment and again at weeks 1, 5 and 10.
measure: Change in ADHD symptom severity total score
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in impulsive behaviour
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in Self/other rating of aggression and emotional lability (SDQ)
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in Clinician rating of compulsivity (Y-BOCS)
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in sleep problems
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in the somatic complaints and side effects describe by the patient.
timeFrame: assessed at weeks 5, 10, and 11.
measure: Change in body composition parameters
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Changes in concentrations of blood biomarkers including hormones, neurotransmitters and nutrients.
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in microbiome composition
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in nutritional intake
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Treatment adherence
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in functioning problems
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Self-rating of emotion regulation difficulties
timeFrame: Baseline assessment and again at weeks 5, and 10.
measure: Change in gastrointestinal symptoms
timeFrame: Baseline assessment and again at weeks 5, 10, and 11.
measure: Change in physical activity: Duration of the activity
timeFrame: Baseline assessment and at week 10.
measure: Change in physical activity: Intensity of the activity
timeFrame: Baseline assessment and at week 10.
measure: Change in neurocognitive measure: Detectability
timeFrame: Baseline assessment and again at weeks 5 and 10.
measure: Change in neurocognitive measure: Omissions
timeFrame: Baseline assessment and again at weeks 5 and 10.
measure: Change in neurocognitive measure: Commissions
timeFrame: Baseline assessment and again at weeks 5 and 10.
measure: Change in neurocognitive measure: Perseverations
timeFrame: Baseline assessment and again at weeks 5 and 10.
measure: Change in neurocognitive measure: Hit Reaction Time (HRT)
timeFrame: Baseline assessment and again at weeks 5 and 10.
measure: Change in neurocognitive measure: Hit Reaction Time Standard Deviation (HRT SD)
timeFrame: Baseline assessment and again at weeks 5 and 10.
measure: Change in neurocognitive measure: Variability
timeFrame: Baseline assessment and again at weeks 5 and 10.
measure: Change in self-rating of perceived stress. The total score ranges from 0-40 with a higher score indicating higher perceived stress. Each item is scored as Never (0), Almost never (1), Sometimes (2), Fairly Often (3), Very Often (4).
timeFrame: Baseline assessment and at week 10.
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt - Goethe Universität
city: Budapest
country: Hungary
facility: Semmelweis University
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
References:
citation: Stoffers-Winterling JM, Storebo OJ, Pereira Ribeiro J, Kongerslev MT, Vollm BA, Mattivi JT, Faltinsen E, Todorovac A, Jorgensen MS, Callesen HE, Sales CP, Schaug JP, Simonsen E, Lieb K. Pharmacological interventions for people with borderline personality disorder. Cochrane Database Syst Rev. 2022 Nov 14;11(11):CD012956. doi: 10.1002/14651858.CD012956.pub2.
citation: Arteaga-Henriquez G, Rosales-Ortiz SK, Arias-Vasquez A, Bitter I, Ginsberg Y, Ibanez-Jimenez P, Kilencz T, Lavebratt C, Matura S, Reif A, Rethelyi J, Richarte V, Rommelse N, Siegl A, Ramos-Quiroga JA. Treating impulsivity with probiotics in adults (PROBIA): study protocol of a multicenter, double-blind, randomized, placebo-controlled trial. Trials. 2020 Feb 11;21(1):161. doi: 10.1186/s13063-019-4040-x.