A Probiotic Strategy for Antipsychotic-induced Metabolic Dysfunction

NCT06729671 | Recruiting

• 1 other identifier: APC175
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Psychosis

Keywords

microbiota; antipsychotic; weight gain

Outcome Measures

Primary Outcomes (2)

• 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.

  change from baseline to 4, 8,12 weeks (end of study) and 18 weeks (washout)

• 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.

  change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)

Secondary Outcomes (5)

• Bifidobacterium longum on waist-to-hip ratio

  change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)

• Bifidobacterium longum on metabolic syndrome markers

  change from baseline to 4, 8, 12 weeks(end of study) and 18 weeks (washout)

• Bifidobacterium longum on cortisol awakening response

  change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)

• Bifidobacterium longum on treatment adherence

  change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)

• Bifidobacterium longum on changes in food intake behavior

  change from baseline to 4,8, 12 weeks (end of study) and 18 weeks (washout)

Other Outcomes (3)

• Bifidobacterium longum on neuroendocrine signalling

  change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)

• Bifidobacterium longum on inflammatory markers

  change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)

• Bifidobacterium longum on gut microbiota

  change from baseline to 4, 8, 12 weeks (end of study) and 18 weeks (washout)

Study Arms (2)

placebo

PLACEBO COMPARATOR

hydroxypropylmethylcellulose (HPMC) capsule with maltidextrin

Dietary Supplement: maltodextrin

active

ACTIVE COMPARATOR

Bifidobacterium longum APC1472 hydroxypropylmethylcellulose (HPMC) capsules

Dietary Supplement: Bifidobacterium longum APC1472 hydroxypropylmethylcellulose (HPMC) capsule

Interventions

Bifidobacterium longum APC1472 hydroxypropylmethylcellulose (HPMC) capsule DIETARY_SUPPLEMENT

Bifidobacterium longum APC1472 capsule

active

maltodextrin DIETARY_SUPPLEMENT

maltodextrin

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patients who are willing to provide blood samples
• Patients who are willing to provide saliva (cortisol) and faecal microbiome samples
• Considering the nature of the study participants, a broad spectrum of concomitant medication will be permissible. Psychotropic meds, including antidepressants, mood stabilisers (lithium, valproate, carbamazepine), hypnotics and benzodiazapines, will be allowed as to not limit recruitment of this type of study participant.

You may not qualify if:

• Intravenous drug use
• Diagnosis of substance dependence in the past 3 months
• Pregnancy or planning a pregnancy
• Antibiotic use in the past 30 days
• Steroid use in the past 30 days
• Use of anti-coagulants, anti-inflammatory drugs, over-the counter non-steroidal anti-inflammatories (NSAIDS) and analgesics. Subjects should have a wash-out period of 4 weeks.
• Patients suffering from any clinically significant or unstable medical condition, including congestive heart failure, coeliac disease, or an immunodeficiency syndrome.
• Pre or probiotic supplements within the past 30 days.

Sponsors & Collaborators

• University College Cork: lead

Study Sites (2)

EIST clinics at St Mary's Primary Care Centre, Gurraunabraher & St Michaels In-Patient unit in the Mercy.

Cork, Ireland

RECRUITING

RISE Metabolic Monitoring Clinics

Cork, Ireland

RECRUITING

MeSH Terms

Conditions

Psychotic Disorders; Weight Gain

Interventions

Capsules; maltodextrin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Harriet Schellekens, PhD

  University College Cork

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harriet Schellekens, PhD

CONTACT

+ 353 (0) 21 420 5429; H.schellekens@ucc.ie

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2024
• First Posted: December 11, 2024
• Study Start: May 16, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: December 11, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IE (2)