Exploring Novel Uses of Microbiota Therapy for Managing the Side Effects of Psychiatric Pharmaceutical Interventions

Exploring Novel Uses of Microbiota Therapy for Managing the Side Effects of Psychiatric Pharmaceutical Interventions: An N-of-1 Pilot and Feasibility Study

To determine the feasibility of whether the addition of key prebiotics administered orally can mitigate some of the most problematic side-effects of the most common psychiatric medications - weight gain and metabolic abnormalities caused by some antidepressants, mood stabilizers and antipsychotics. In the initial part of the study, we aim to determine feasibility of the study and evaluate participant compliance.

Our clinical trial will encourage the growth of Akkermansia muciniphila (AM) through enteric-coated orally-administered acetate (apple cider vinegar powder in capsules) in 16-to-28 year-old patients who have already experienced weight gain while on stable doses of psychiatric medication, with the hypothesis that the addition of this prebiotic will result in alterations in gut microbiota and measurable weight loss, as well as improvement in metabolic measurements.

Primary Objective:

• To evaluate feasibility of using acetate in a large-scale clinical trial, including considerations for protocol, study agent, recruitment, retention, adverse events, budget, staff, facility, and patient experience
• To estimate effect size of change in AM relative abundance by measuring pre- and post-intervention levels for use in designing future large-scale clinical trials

Secondary Objectives:

• To determine whether acetate administered orally shows an observable effect on weight gain as a side effect from antidepressants, mood stabilizers, and/or antipsychotics in a sample of participants already on stable doses of at least one of these medications
• To determine changes in metabolic syndrome profile, as indicated by blood pressure and high-density lipoprotein.
• To conduct preliminary analyses on any possible changes in mood/anxiety symptoms pre- versus post-intervention
• To identify and define other potential confounders or effect modifiers of our primary and secondary objectives that should be considered in future study designs

Study Overview

• Status: Recruiting
• Conditions: Depression, Anxiety
• Intervention / Treatment: Dietary supplement: Acetate (Apple Cider Vinegar)

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Elizabeth Osuch, MD; Phone Number: 65188 519-646-6000; Email: elizabeth.osuch@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 3H8
      • Recruiting
      • First Episode Mood and Anxiety Disorders Program (FEMAP)
      • Contact: Elizabeth A Osuch, MD; Phone Number: 65188 +1-519-646-6000; Email: FEMAP@lhsc.on.ca
      • Sub-Investigator: David M Walton, PhD
      • Sub-Investigator: Jeremy P Burton, PhD
      • Sub-Investigator: Colleen O'Connor, PhD
      • Sub-Investigator: Ju Eun Lee, MB, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For an eligible patient, all inclusion criteria must be answered "yes"

1. Signed informed consent obtained prior to any study-related activities
2. Patients of FEMAP who are between the ages of 16 and 28
3. Currently on a stable dose of an antidepressant, mood stabilizer, and/or antipsychotic drug AND have experienced what they deem to be problematic weight gain (approximately greater than 5% of initial body weight) that was temporally linked with initiating the drug, as confirmed by a psychiatrist
4. Have a body mass index of ≥ 21.7 kg/m2 (midpoint of normal BMI (18.5-24.9).

Exclusion Criteria:

1. Participants who are unable to follow multi-step instructions independently, as determined by the treating psychiatrist.
2. Participants who are pregnant or planning to get pregnant
3. Patients on medications that have weight loss as a potential side effect i.e. topiramate, metformin, psychostimulants.
4. Current active eating disorder i.e. bulimia nervosa, binge eating disorder, anorexia nervosa
5. Currently on a weight-loss diet plan i.e. ketogenic diet, detox diet
6. Currently using a medication for weight loss i.e. Contrave (bupropion / naltrexone), Saxenda (liraglutide)
7. Current use of dietary supplements for weight loss i.e. garcinia cambogia; or use within 4 weeks prior to study initiation
8. Bowel surgery
9. Crohn's disease or other bowel conditions
10. Blood/bleeding/liver/kidney disorders
11. Currently enrolled in other clinical trial which may affect their study outcome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transition-Age Adults; 16-25 year old patients on stable dose of antipsychotic medication for treatment of depression or anxiety.	Dietary supplement: Acetate (Apple Cider Vinegar); Consumer-grade apple cider vinegar (ACV) capsules will have extra enteric coating applied for delivery further into the GI tract.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility: Recruitment success	Number of potential participants approached to number expressing interest, and number invited to number recruited (recruitment success)	5 months
Feasibility: Retention	Number recruited to number retained (attrition)	5 months
Feasibility: Adherence	Number adhering to intervention protocol quantified through number of capsules returned at end of trial	5 months
Feasibility: Adverse Events	A study-specific data form for collecting adverse events	5 months
Akkermansia Muciniphila abundance	Relative abundance (proportion) of AM in stool at inception compared to all other species identified, and change in relative abundance from pre- to post-intervention	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight	Standard Medical-grade floor scale	5 months, recorded monthly
Metabolic Indicator: Blood pressure	Blood pressure using medical-grade arm cuff (mm/Hg, Systolic and Diastolic)	5 months
Metabolic Indicator: High-Density Lipoproteins	HDL cholesterol assayed from antecubital blood draw, expressed in mg/dL	5 months
Mood: Depression	Quick Inventory of Depressive Symptomatology (QIDS-SR, Rush et al. 2003) - baseline scores to describe the sample, change from pre-post intervention to explore potential treatment effect	5 months, captured monthly
Mood: Anxiety	Overall Anxiety Severity and Impairment Scale (OASIS, Barlow et al. 2010) - baseline scores to describe the sample, change from pre-post intervention to explore potential treatment effect	5 months, captured monthly

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Probiotics; Psychiatry; Weight
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Anti-Infective Agents; Anti-Bacterial Agents; Acetic Acid
• Other Study ID Numbers: 119638

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not plan to share IPD with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No