Combined Cytidine and Creatine-containing Drug in the Treatment of the Bipolar Depression

Study Overview
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Brief Summary
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This research is aimed to investigate the efficacy and safety of the creatine and cytidine augmentation in treating bipolar depression and to evaluate changes in relevant brain biochemical metabolism using proton and phosphorous magnetic resonance spectroscopy.

Official Title
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A Double-Blind, Placebo-Controlled Trial of Combined Cytidine- and Creatine-containing Drug and Dietary Supplement in the Treatment of the Bipolar Depression

Conditions
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Depression, Bipolar

Intervention / Treatment
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* Drug: Valproate and Placebo
* Drug: Valproate and Cytidine-containing Drug
* Drug: Valproate and Creatine-containing Drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 19-65 years Bipolar disorder I or II (DSM-IV-TR) with current depressive episode Informed consent Exclusion Criteria: Use of medication for bipolar depression or other psychotropic drugs Current Axis I mental disorders other than bipolar depression based on structured clinical interview Current borderline or antisocial personality disorder based on structured clinical interview Major medical or neurological illnesses (epilepsy, multiple sclerosis, brain tumor, cerebrovascular disease, etc) Hypersensitivity to divalproate or valpromide Diagnosis of porphyria Current or past liver diseases Severe dysfunction in liver or pancreas Use of mefloquine Alcohol or substance abuse/dependence Intelligence quotient of 80 or below Contraindications to magnetic resonance imaging Pregnancy or breastfeeding Allergy or intolerance to the study drugs

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Valproate and Placebo<br>Valproate: 300mg/day for 8 weeks Placebo: for 8 weeks | Drug: Valproate and Placebo<br> <br> |
| Experimental: Valproate and Cytidine-containing Drug<br>Valproate: 300mg/day for 8 weeks Cytidine-containing Drug: 2g/day for 8 weeks | Drug: Valproate and Cytidine-containing Drug<br> <br> |
| Experimental: Valproate and Creatine-containing Drug<br>Valproate: 300mg/day for 8 weeks Creatine-containing Drug: 3g/day for the first week 5g/day for week 2-8 | Drug: Valproate and Creatine-containing Drug<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in symptoms of bipolar depression | assessed with structured clinical interview | Baseline and 8 weeks | 
| Change in depressive symptoms | assessed with structured clinical interview | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain Glx (glutamate+glutamine) level | assessed with proton magnetic resonance spectroscopy | Baseline and 8 weeks | 
| Change in brain phosphocreatine level | assessed with phosphorous magnetic resonance spectroscopy | Baseline and 8 weeks | 
| Number of participants with adverse events |  | Baseline through 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar depression, Cytidine, Creatine, Magnetic resonance spectroscopy