Inositol for Comorbid Anxiety in Children and Adolescents With Bipolar Disorder

Study Overview
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Brief Summary
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This is an open trial that seeks to determine the safety and tolerability of using inositol for children and adolescents with bipolar disorder and comorbid anxiety disorders with an exploration of efficacy and dose-response.

Detailed Description
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Anxiety disorders are common comorbidities among children and adolescents with bipolar disorder. Treatment with standard pharmacologic agents may worsen mood problems or lead to drug dependency. Inositol has shown benefits for bipolar depression in adults. This is an open multi-case control study. The investigators will enroll 20 children and adolescents ages 8-17 treated at the Child and Adolescent Bipolar Services (CABS) at Western Psychiatric Institute and Clinic. Participants' involvement will be 14 weeks, including the initial titration of the supplement, maintenance, and taper. Primary outcomes will include standard measures of mood and anxiety. Also, physiologic measures including body mass index and bedside glucose will be followed.

Official Title
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Inositol for Comorbid Anxiety in Children and Adolescents With Bipolar Disorder

Conditions
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Bipolar Disorder, Anxiety Disorders, Anxiety

Intervention / Treatment
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* Drug: Inositol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence in the medical record confirming the DSM-V diagnosis of bipolar disorder. If this documentation is not in the record, then the appropriate sections of K-SADS will be administered to confirm the diagnosis. Evidence in the medical record confirming the DSM-V diagnosis of anxiety disorder including; separation anxiety disorder, generalized anxiety disorder, and/or social phobia. If this documentation is not present or is more than 2 years old, then the appropriate section of the K-SADS will be administered to confirm diagnosis. At least moderate severity of anxiety symptoms as determined by score of ≥ 13 on the Pediatric Anxiety Rating Scale (PARS). On a stable dose of psychotropic medications for at least one month, with no major changes projected. Exclusion Criteria: Presence of prominent diarrhea. Diagnosis of diabetes mellitus. Presence of active suicidal ideation and behavior or psychosis. B-SSRS ideation score greater than 1. B-SSRS behavior score greater than 0. Weight less than 20 kg. Known pregnancy.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inositol<br>Subjects will receive inositol | Drug: Inositol<br>* Subjects will receive inositol<br>* Other names: Myoinositol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the safety of myo-inositol, anxiety and mood symptoms will be measured using Clinical Global Impression Severity (CGI-S). | This assessment rates the clinician's view of the patient's anxiety severity prior to and after initiating myo-inositol. Scores range from 0-7. Higher scores mean worse outcome. | Weeks 1-12 | 
| To measure the safety of myo-inositol, anxiety and mood symptoms will be measured using the Patient Global Index of Change Severity (PGIC-S). | This scale is a parent and child report tool that evaluates participants' anxiety and assesses if there has been a decline in clinical status. Answer options are 0-None, 1-Mild, 2-Moderate, and 3-Severe and describe symptoms of anxiety. Higher scores mean worse outcome. | Weeks 1-12 | 
| To measure the tolerability of myo-inositol, the number of participants who are able to remain on myo-inositol for the full treatment period (10-12 weeks) will be measured. | At study completion, the number of participants who remained on myo-inositol for the full 10-12 weeks will be counted. | Weeks 1-14 | 
| To measure the tolerability of myo-inositol, the number of participants able to remain on the full dosage of myo-inositol for the full treatment period (10-12 weeks) will be measured. | Participants will be titrated up to the full dose of myo-inositol by Week 3 and will remain on the full dose for 6 weeks unless they cannot tolerate the dose. At study completion, the number of participants who remained on the full-dose of myo-inositol for the full 10-12 weeks will be counted. | Weeks 3-8 | 
| To measure the safety and tolerability of myo-inositol, a change from baseline on the Physical Symptom Checklist (Side Effect Rating Scale) will be measured. | This assessment is a parent and child report measure. Its scores range from 0 to 60. Higher scores are indicative of more physical and psychological symptoms and worse outcome. | Weeks 1-14 | 
| To measure the safety of myo-inositol, the Brief Suicide Severity Rating Scale (B-SSRS) will be measured at each visit. | The B-SSRS probes for suicidal thoughts and behavior. The scores for both categories range from 0-5. If participants score greater than 1 on B-SSRS ideation or greater than 0 on B-SSRS behavior, then they cannot be enrolled or remain in the study. Higher scores mean worse outcome. | Weeks 1-12 | 
| To measure the safety of myo-inositol, a fingerstick blood test will be done to measure glucose levels at the first and final study visits. | A glucometer will be used to test the blood glucose levels of participants. | Week 1 & Week 10-12 | 
| To measure the safety of myo-inositol, physical measurements (height and weight) will be obtained. | Myo-inositol is dosed by the weight of the participant. To make sure the participant is taking the correct dose, weight will be measured at each study visit. Height will only be measured at Week 1 to calculate BMI. Also, change in weight or BMI will be followed. | Weeks 1-12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the effectiveness of myo-inositol for mood symptoms, a change from baseline on the Moods and Feelings Questionnaire (MFQ) will be evaluated. | The Mood and Feelings Questionnaire (MFQ) is a child and parent report questionnaire that measures depressive symptoms in children and young adults. Scores range from 0 to 66. Higher score are indicative of increased depressive symptom severity and worse outcome. | Weeks 1-12 | 
| To measure the effectiveness of myo-inositol for anxiety symptoms, a change from baseline on Clinical Global Impression Improvement (CGI-I) will be evaluated. | This assessment rates the clinician's view of the patient's anxiety improvement after initiating myo-inositol. Scores range from 0-7. Higher scores mean worse anxiety symptoms. | Weeks 2-12 | 
| To measure the effectiveness of myo-inositol for anxiety symptoms, a change from baseline on Clinical Global Impression Severity (CGI-S) will be evaluated. | This assessment rates the clinician's view of the patient's anxiety severity before and after initiating myo-inositol. Scores range from 0-7. Higher scores mean more anxiety symptoms. | Weeks 2-12 | 
| To measure the effectiveness of myo-inositol for anxiety symptoms, a change from baseline on Brief Child Mania Rating Scale Parent Version (BCMRS-P) will be evaluated. | The BMRS-P is a 10-item inventory rated on a 4 point Likert type scale anchored by 0 (never/rare), 1 (sometimes), 2 (often), and 3 (very often). Its purpose is to measure changes in symptoms of pediatric bipolar disorder (PBD) as they change over time. Scores range from 0 to 30. Higher scores mean more symptom severity. | Week 1 & Weeks 10-12 | 
| To measure the effectiveness of myo-inositol for anxiety symptoms, a change from baseline on the Patient Global Index of Change Improvement (PGIC-I) will be evaluated. | This scale evaluates participants' anxiety and assesses if there has been an improvement in clinical status. Answer options are Much Improved, Minimally Improved, No Change, Minimally Worse, and Much Worse. | Weeks 2-12 | 
| To measure the effectiveness of myo-inositol for anxiety symptoms, a change from baseline on the Patient Global Index of Change Severity (PGIC-S) will be evaluated. | This scale is a child and parent self-report instrument used to evaluate participants' anxiety and assesses if there has been a decline in clinical status. Answer options are 0-None, 1-Mild, 2-Moderate, and 3-Severe and describe symptoms of anxiety. Higher scores mean more anxiety symptoms and worse outcome. | Weeks 1-12 | 
| To measure the effectiveness of myo-inositol for anxiety symptoms, a change from baseline on the Self-Report for Childhood Related Emotional Disorders (SCARED) will be evaluated. | The SCARED is a child and parent self-report instrument used to screen for childhood anxiety disorders including general anxiety disorder, separation anxiety disorder, panic disorder, and social phobia. The SCARED consists of 41 items and 5 factors that parallel the DSM-IV classification of anxiety disorders. Scores range from 0-82. Scores greater than or equal to 25 indicate the presence of an anxiety disorder and scores in different items indicate the type of anxiety disorder. | Weeks 1-12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inositol