A Probiotic Strategy for Antipsychotic-induced Metabolic Dysfunction
ConditionPsychosis
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorUniversity College Cork
About this trial
Antipsychotic drugs are used to treat a range of psychiatric disorders including schizophrenia, bipolar disorders, and psychotic depression. Most antipsychotics are associated with significant weight gain and metabolic disturbances, which increase the risks for other diseases (obesity, diabetes, coronary diseases, etc.) and negatively impact medication adherence and quality of life. Evidence has shown that Olanzapine, for example, increases appetite, food intake, and food reward and modulates the gut microbiota. The gut microbiota can modulate adiposity, metabolism and immune-endocrine signals that impact host's energy balance and feeding behaviour. This, together with the fact that antipsychotic-induced remodelling of the gut microbiota has been associated with weight gain, suggests that microbiota-targeted interventions could help to alleviate or prevent the distressing side-effects of antipsychotic medications. The investigators have previously published promising data demonstrating anti-obesity effects of a novel Bifidobacterium longum APC1472, in a mouse model of obesity and in an overweight/obese population of humans, reducing levels of glucose and normalizing ghrelin levels. Because atypical antipsychotic medications are often used in people experiencing psychosis and the mechanisms of antipsychotic-induced weight gain and metabolic dysfunction have been suggested to include glucose intolerance (hyperglycaemia) and aberrant ghrelin signalling, the investigators propose to assess if adjunct supplementation of Bifidobacterium longum APC1472 can attenuate weight gain and metabolic side-effects associated with the use of atypical antipsychotic medication in people with non- affective psychosis. The investigators propose an exploratory patient-oriented research study, to assess the potential of adjunct Bifidobacterium longum APC1472 supplementation in individuals with psychosis receiving antipsychotic treatment, to ameliorate the liability to gain weight and/or normalize metabolic disturbances. Findings from this study will support clinical decision-making, increasing patient choice, and increase medication adherence, which will ultimately improve health and quality of life, and overall wellbeing of individuals as they pass through normal life stages.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
8.1 Inclusion Criteria To be considered eligible for enrolment into the study, subjects must;
Aged between 18-65 years old including women of child-bearing age
Having a diagnosis of affective or non-affective functional psychosis defined according to ICD-10 criteria for psychosis (codes F20-30 & F32.3)
Patients who are able to and have given written informed consent
Disqualifiers
Intravenous drug use
Diagnosis of substance dependence in the past 3 months
Pregnancy or planning a pregnancy
Antibiotic use in the past 30 days
Trial design
Design model
Parallel
Treatments tested in this trial
Bifidobacterium longum APC1472 hydroxypropylmethylcellulose (HPMC) capsule
Dietary supplementBifidobacterium longum APC1472 capsule
maltodextrin
Dietary supplementmaltodextrin
Treatment groups
70 Participants
are divided into 2 treatment groupsGroup A: placeboPlacebo comparator 1 intervention
Group B: activeActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Bifidobacterium longum on weight gain
Investigate if supplementation with Bifidobacterium longum APC1472 capsules can attenuate weight gain in male and female human patients with psychosis treated with antipsychotics (olanzapine, clozapine, risperidone, paliperidone, aripiprazole, cariprazine and quetiapine). Primary outcome is the comparative end-point body weight (kg) between the placebo and probiotic groups to determine the effect of supplementation on antipsychotic-induced weight gain.
Time frame
change from baseline to 4, 8,12 weeks (end of study) and 18 weeks (washout)2
Bifidobacterium longum on glucose levels.
Investigate if supplementation with Bifidobacterium longum APC1472 capsules can attenuate fasting levels of glucose in male and female human patients with psychosis treated with antipsychotics (olanzapine, clozapine, risperidone, paliperidone, aripiprazole, cariprazine and quetiapine). Primary outcome is the comparative fasted glucose levels (measured in mg/dL or mmol/L) between the placebo and probiotic groups to determine the effect of supplementation on antipsychotic-induced high glucose levels.
Time frame
change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)Secondary outcomes
1
Bifidobacterium longum on waist-to-hip ratio
• Effect of APC1472 on waist-to-hip ratio
Time frame
change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)2
Bifidobacterium longum on metabolic syndrome markers
Markers related to metabolic syndrome and cardiometabolic function analysed (Blood pressure, HbA1C, cholesterol, LDL, HDL, triglycerides Cholesterol), measured in mg/dL or mmol/L, pg/mL, (mmHg), mmol/mol or percent (%), where appropriate.
Time frame
change from baseline to 4, 8, 12 weeks(end of study) and 18 weeks (washout)3
Bifidobacterium longum on cortisol awakening response
• Saliva samples assessed for cortisol awakening response (µg/dL or nmmol/L) and correlated with weight gain and metabolic markers.
Time frame
change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)4
Bifidobacterium longum on treatment adherence
Improvement in treatment adherence analysed using questionnaires (self-rated scales).
Time frame
change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)Other outcomes
1
Bifidobacterium longum on neuroendocrine signalling
• Exploratory outcomes measuring endocrine hormones, including ghrelin (active and total), leptin, insulin, PYY, GLP-1 (active and total) in pmol/L or pg/mL.
Time frame
change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)2
Bifidobacterium longum on inflammatory markers
• Exploratory outcomes measuring C-peptide (CRP), and other inflammatory cytokine levels (IFNγ, Il-4, IL-6 Il-10, TNF-a) in pmol/L or pg/mL.
Time frame
change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)3
Bifidobacterium longum on gut microbiota
Microbiota analysis using shotgun metagenomic analysis, to investigate the impact of Bifidobacterium longum APC1472 supplementation on the gut microbiota composition, diversity and volatility in human patients treated with antipsychotics. Analysis will use taxonomic and functional readouts, including alpha and beta diversity index.
Time frame
change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)Sponsors and contacts
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Source ClinicalTrials.gov