Adjunctive Curcumin for Symptomatic Adolescents With Bipolar Disorder: Brain and Body Considerations

Study Overview
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Brief Summary
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This study will enroll 30 adolescents with bipolar disorder (BD) who are suffering from symptoms of depression despite already taking a traditional mood-stabilizing medication. Curcumin will be added to their current medications for 8 weeks. During these 8 weeks, their mood symptoms will be assessed regularly. Height, weight, and blood pressure will also be measured repeatedly. Blood tests will be completed before treatment, after 4 weeks of treatment, and at the end of the study. Blood tests will allow us to determine whether changes in inflammation and oxidative stress explain curcumin's effect on mood. Finally, we will use sophisticated technology to measure blood vessel functioning. We have three main predictions: 1. Curcumin will improve mood symptoms without causing physical problems; 2. Curcumin will reduce inflammation and oxidative stress, and these reductions will be linked to improvements in mood; 3. Curcumin will improve blood vessel functioning, and these improvements will be linked to improved inflammation and oxidative stress.

Official Title
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Adjunctive Curcumin for Symptomatic Adolescents With Bipolar Disorder: Brain and Body Considerations

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Curcumin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English speaking all races and ethnicities bipolar disorder I or II currently treated with lithium, divalproex, lamotrigine, and/or second generation antipsychotic doses stable for greater than or equal to 4 weeks current CGI BP score of moderate or greater current CDRS-R severity of greater than or equal to 35 Exclusion Criteria: If female, pregnant or sexually active without reliable contraception significant suicidal ideations (as determined by clinical interview or CDRS-R > 3) and/or any suicidal intent, even if fleeting or non-recurrent, in the preceding 2 weeks substance dependence within the past 2 months daily antidepressant, glucocorticoid, nonsteroidal anti-inflammatory, anti-platelet, anti-coagulant, antacid, or oral hypoglycemic medication or insulin; high-dose antioxidant vitamin supplements or other natural health products that may function as an antidepressant within 30 days of baseline IQ<80 or autistic disorder full threshold mania and/or YMRS > 20 and/or psychosis hypersensitivity to curcumin/turmeric, gelatin dietary consumption of curcumin/turmeric > 3 times/week clinically significant or unstable medical disorder; known gallstones and/or bile duct obstruction, stomach ulcers, excessive stomach acid/heartburn/gastroesophageal reflux disease (GERD); or clinically significant baseline laboratory abnormalities; or ALT and /or AST above the upper limit of normal on repeat examination at baseline severe depression (CDRS-R > 98) and/or severely ill (CGI BP >5)

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 19 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: adjunctive curcumin<br>Curcumin will be added to their current medications for 8 weeks. Starting dose will be 500mg daily, increased to 500mg twice daily in week 2, then increased to 1000mg twice daily during weeks 3-8. A slower titration will be used for subjects who demonstrate tolerability problems. | Drug: Curcumin<br> <br> * Other names: turmeric;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Children's Depression Rating Scale - Revise (CDRS-R) | Measures mood symptom severity. Response is defined as greater than or equal to 50% reduction in CDRS-R score. | Change from baseline to endpoint (assessed at weeks 0, 2, 4, 6, 8) | 
| Oxidative Stress Markers | Obtained through blood work | Change from baseline to endpoint (measured at weeks 0, 4, 8) | 
| Pro-Inflammatory Markers | Obtained through blood work | Change from baseline to endpoint (measured at weeks 0, 4, 8) | 
| Endothelial Function | Will be assessed via RH-PAT using the EndoPAT | Change from baseline to endpoint (measured at weeks 0, 4, 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Bipolar Disorder Version (CGI BP) | Measures overall illness severity. Remission is defined as an improvement score of 1 or 2. | Change from baseline to endpoint (assessed at weeks 0, 2, 4, 6, 8) | 
| KSADS Depression Section (KDRS) | Measures mood symptoms severity | Change from baseline to endpoint (assessed at weeks 0, 2, 4, 6, 8) | 
| KSADS Mania Rating Scale (KMRS) | Measures symptoms severity | Change from baseline to endpoint (assessed at weeks 0, 2, 4, 6, 8) | 
| Young Mania Rating Scale (YMRS) | Measures symptom severity | Change from baseline to endpoint (assessed at weeks 0, 2, 4, 6, 8) | 
| Screen for Child Anxiety Related Emotional Disorders (SCARED) | Anxiety self-report | Change from baseline to endpoint (assessed at weeks 0, 2, 4, 6, 8) | 
| Weight Gain | Significant weight gain is greater than or equal to 7% of baseline weight | Change from baseline to endpoint (measured at 0, 4, 8) | 
| Blood Pressure |  | Change from baseline to endpoint (measured at 0, 4, 8) | 
| Side Effects for Children and Adolescents (SEFCA) | SEFCA is a questionnaire that assesses side effects. We anticipate that no major side-effects will have a prevalence of greater than 20%. | Change from baseline to endpoint (assessed at weeks 0, 4, 6, 8) |