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

Study Overview
=================
Brief Summary
-----------------
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

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

Conditions
-----------------
Depression, Anxiety

Intervention / Treatment
-----------------
* Dietary Supplement: Acetate (Apple Cider Vinegar)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For an eligible patient, all inclusion criteria must be answered yes Signed informed consent obtained prior to any study-related activities Patients of FEMAP who are between the ages of 16 and 28 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 Have a body mass index of ≥ 21.7 kg/m2 (midpoint of normal BMI (18.5-24.9). Exclusion Criteria: Participants who are unable to follow multi-step instructions independently, as determined by the treating psychiatrist. Participants who are pregnant or planning to get pregnant Patients on medications that have weight loss as a potential side effect i.e. topiramate, metformin, psychostimulants. Current active eating disorder i.e. bulimia nervosa, binge eating disorder, anorexia nervosa Currently on a weight-loss diet plan i.e. ketogenic diet, detox diet Currently using a medication for weight loss i.e. Contrave (bupropion / naltrexone), Saxenda (liraglutide) Current use of dietary supplements for weight loss i.e. garcinia cambogia; or use within 4 weeks prior to study initiation Bowel surgery Crohn's disease or other bowel conditions Blood/bleeding/liver/kidney disorders Currently enrolled in other clinical trial which may affect their study outcome

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 25 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: N-of-1 type prospective study
Masking: None (Open Label)


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Probiotics, Psychiatry, Weight