## Protocol Section
### Identification Module
**NCT ID:** NCT02625779

**Brief Title:** Combined Cytidine and Creatine-containing Drug in the Treatment of the Bipolar Depression

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

#### Organization Study ID Info
**ID:** NARSAD_Bipolar
#### Organization
**Class:** OTHER
**Full Name:** Ewha Womans University Mokdong Hospital
### Status Module
#### Completion Date
**Date:** 2017-04-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2018-02-09

**Type:** ACTUAL

**Last Update Submit Date:** 2018-02-08

**Overall Status:** WITHDRAWN

#### Primary Completion Date
**Date:** 2017-04-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2016-03-01

**Type:** ESTIMATED

**Status Verified Date:** 2018-02

#### Study First Post Date
**Date:** 2015-12-09
**Type:** ESTIMATED
**Study First Submit Date:** 2015-12-07
**Study First Submit QC Date:** 2015-12-07
**Why Stopped:** The research project has been cancelled before any participants were enrolled.
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Ewha Womans University Mokdong Hospital

#### Responsible Party

**Investigator Affiliation:** Ewha Womans University Mokdong Hospital

**Investigator Full Name:** In Kyoon Lyoo

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** 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.

### Conditions Module

**Conditions:**

- Depression, Bipolar

**Keywords:**

- Bipolar depression

- Cytidine

- Creatine

- Magnetic resonance spectroscopy

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Valproate: 300mg/day for 8 weeks Placebo: for 8 weeks

**Intervention Names:**

- Drug: Valproate and Placebo

**Label:** Valproate and Placebo

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Valproate: 300mg/day for 8 weeks Cytidine-containing Drug: 2g/day for 8 weeks

**Intervention Names:**

- Drug: Valproate and Cytidine-containing Drug

**Label:** Valproate and Cytidine-containing Drug

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Valproate: 300mg/day for 8 weeks Creatine-containing Drug: 3g/day for the first week 5g/day for week 2-8

**Intervention Names:**

- Drug: Valproate and Creatine-containing Drug

**Label:** Valproate and Creatine-containing Drug

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Valproate and Placebo

**Name:** Valproate and Placebo

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Valproate and Cytidine-containing Drug

**Name:** Valproate and Cytidine-containing Drug

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Valproate and Creatine-containing Drug

**Name:** Valproate and Creatine-containing Drug

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** assessed with structured clinical interview

**Measure:** Change in symptoms of bipolar depression

**Time Frame:** Baseline and 8 weeks

**Description:** assessed with structured clinical interview

**Measure:** Change in depressive symptoms

**Time Frame:** Baseline and 8 weeks

#### Secondary Outcomes

**Description:** assessed with proton magnetic resonance spectroscopy

**Measure:** Change in brain Glx (glutamate+glutamine) level

**Time Frame:** Baseline and 8 weeks

**Description:** assessed with phosphorous magnetic resonance spectroscopy

**Measure:** Change in brain phosphocreatine level

**Time Frame:** Baseline and 8 weeks

**Measure:** Number of participants with adverse events

**Time Frame:** Baseline through 8 weeks

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 65 Years

**Minimum Age:** 19 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Seoul

**Country:** Korea, Republic of

**Facility:** Ewha Womans University Mokdong Hospital

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001526

- Term: Behavioral Symptoms

- ID: D000019964

- Term: Mood Disorders

- ID: D000001523

- Term: Mental Disorders

- ID: D000068105

- Term: Bipolar and Related Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7058

- Name: Depression

- Relevance: HIGH

- As Found: Depression

- ID: M7061

- Name: Depressive Disorder

- Relevance: HIGH

- As Found: Depression

- ID: M4996

- Name: Bipolar Disorder

- Relevance: HIGH

- As Found: Bipolar Depression

- ID: M4818

- Name: Behavioral Symptoms

- Relevance: LOW

- As Found: Unknown

- ID: M21835

- Name: Mood Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M226

- Name: Bipolar and Related Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003863

- Term: Depression

- ID: D000003866

- Term: Depressive Disorder

- ID: D000001714

- Term: Bipolar Disorder

### Intervention Browse Module - Ancestors

- ID: D000000927

- Term: Anticonvulsants

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000018682

- Term: GABA Agents

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018692

- Term: Antimanic Agents

- ID: D000014149

- Term: Tranquilizing Agents

- ID: D000002492

- Term: Central Nervous System Depressants

- ID: D000011619

- Term: Psychotropic Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: AntiConv

- Name: Anticonvulsants

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: PsychDr

- Name: Psychotropic Drugs

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M17383

- Name: Valproic Acid

- Relevance: HIGH

- As Found: Immediate release

- ID: M4246

- Name: Anticonvulsants

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

- ID: M14474

- Name: Psychotropic Drugs

- Relevance: LOW

- As Found: Unknown

- ID: T385

- Name: Creatine

- Relevance: HIGH

- As Found: Elbow

### Intervention Browse Module - Meshes

- ID: D000014635

- Term: Valproic Acid

### Misc Info Module

- Version Holder: 2024-05-24
