## Protocol Section
### Identification Module
**NCT ID:** NCT00560079

**Brief Title:** Efficacy of Allopurinol and Dypiridamole in Acute Mania

**Official Title:** A Double-blind, Randomized, Placebo-controlled 4-week Study on the Efficacy and Safety of the Purinergic Agents Allopurinol and Dipyridamole in Acute Bipolar Mania.

#### Organization Study ID Info
**ID:** 03T-356
#### Organization
**Class:** OTHER
**Full Name:** Hospital Espirita de Porto Alegre
### Status Module
#### Completion Date
**Date:** 2006-04

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2016-08-16

**Type:** ESTIMATED

**Last Update Submit Date:** 2016-08-15

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2005-04

**Type:** ACTUAL

#### Start Date
**Date:** 2003-11

**Status Verified Date:** 2016-08

#### Study First Post Date
**Date:** 2007-11-19
**Type:** ESTIMATED
**Study First Submit Date:** 2007-11-15
**Study First Submit QC Date:** 2007-11-15
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Stanley Medical Research Institute

#### Lead Sponsor

**Class:** OTHER

**Name:** Hospital Espirita de Porto Alegre

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study aims to evaluate the potential antimanic efficacy, safety and tolorability of the purinergic agents allopurinol and dipyridamole as an add-on treatment to lithium in a sample of 180 drug-free manic patients enrolled in a double-blind, placebo-controlled design.

**Detailed Description:** Men and women ages 18 to 65 years, who were inpatients with a diagnosis of manic episode were recruited at the emergency room of Espirita Hospital of Porto Alegre (HEPA), Brazil (n=180) between September 2004 and 2006. The presence of manic episode was confirmed using SCID-I and the severity of episode was evaluated using the Young Mania Rating Scale (YMRS) and the Clinical Global Impression scale (CGI). Patients were required to present a score\>22 on the YMRS at screening to be included. Subjects presenting rapid cycling, mixed episodes and comorbidities with axis I psychiatric disorders were not considered for inclusion. All subjects presented good physical health determined by physical exam, medical history, blood screening and electrocardiogram. Patients were randomly assigned to allopurinol 600 mg/day, dipyridamole 200mg or placebo as add-on medication lithium treatment for a 4-week, double-blind trial. The use of adjunctive antipsychotic agents (typical or second-generation drugs) was not allowed during the double-blind period. Adjunctive diazepam was used when necessary (maximum dose=20mg/day). Raters (psychiatrists) were trained together to establish reliability (YMRS =0.90). This study was approved by the Espirita Hospital Ethics Committee-IRB. Written informed consent was obtained from all patients and/or family member. Possible adverse events were monitored weekly during the follow-up period. Regarding primary outcome measures, we compared the percentage of responders according YMRS score decrease of at least 50% among allopurinol, dipyridamole and placebo groups, using fisher exact test. Also, the percentage of improvement from baseline to endpoint was obtained and compared among groups using analysis of variances (one-way ANOVA) with Duncan post-hoc test. Remission rates (YMRS scores \< 12) were also analyzed. P values \< 0.05 were considered statistically significant. Besides completers analysis, intention to treat and LOCF were employed to include data from drop-out patients who were evaluated at visit 3. Possible correlations were measured using Pearson test. Fischer exact test and X2 evaluated response and remission rates. Data are presented as mean ± standard deviation.

### Conditions Module

**Conditions:**

- Mania

### 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

**Count:** 180

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Lithium 900mg/day plus allopurinol 600mg/day

**Intervention Names:**

- Drug: Allopurinol

**Label:** 1

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: Dipyridamole

**Label:** 2

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Intervention Names:**

- Drug: Placebo

**Label:** 3

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- 1

**Description:** Allopurinol 600mg/day bid for 28 days

**Name:** Allopurinol

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- 2

**Description:** Dipyridamole 200mg/day bid for 28 days

**Name:** Dipyridamole

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- 3

**Description:** Placebo

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** This study aimed to evaluate the potential antimanic efficacy, safety and tolerability

**Time Frame:** 28 days

#### Secondary Outcomes

**Measure:** Plasma uric acid levels

**Time Frame:** 28 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* The presence of manic episode was confirmed using SCID-I and the severity of episode was evaluated using the Young Mania Rating Scale (YMRS) and the Clinical Global Impression scale (CGI). Patients were required to present a score\>22 on the YMRS at screening to be included.All subjects presented good physical health determined by physical exam, medical history, blood screening and electrocardiogram

Exclusion Criteria:

* Subjects presenting rapid cycling, mixed episodes and comorbidities with axis I psychiatric disorders were not considered for inclusion. .

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Porto Alegre

**Country:** Brazil

**Facility:** Hospital Espirita de Porto Alegre

**State:** RS

**Zip:** 91720-440

#### Overall Officials

**Official 1:**

**Affiliation:** Staff Member

**Name:** Rodrigo Machado-Vieira, MD, MSc, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Machado-Vieira R, Soares JC, Lara DR, Luckenbaugh DA, Busnello JV, Marca G, Cunha A, Souza DO, Zarate CA Jr, Kapczinski F. A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania. J Clin Psychiatry. 2008 Aug;69(8):1237-45. doi: 10.4088/jcp.v69n0806.

**PMID:** 18681754

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000019954

- Term: Neurobehavioral Manifestations

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M2598

- Name: Mania

- Relevance: HIGH

- As Found: Mania

- ID: M21826

- Name: Neurobehavioral Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000087122

- Term: Mania

### Intervention Browse Module - Ancestors

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000006074

- Term: Gout Suppressants

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000016166

- Term: Free Radical Scavengers

- ID: D000000975

- Term: Antioxidants

- ID: D000020011

- Term: Protective Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000010726

- Term: Phosphodiesterase Inhibitors

- ID: D000010975

- Term: Platelet Aggregation Inhibitors

- ID: D000014665

- Term: Vasodilator Agents

### Intervention Browse Module - Browse Branches

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: PsychDr

- Name: Psychotropic Drugs

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: PlAggInh

- Name: Platelet Aggregation Inhibitors

### Intervention Browse Module - Browse Leaves

- ID: M19022

- Name: Lithium Carbonate

- Relevance: LOW

- As Found: Unknown

- ID: M3834

- Name: Allopurinol

- Relevance: HIGH

- As Found: BIA

- ID: M7358

- Name: Dipyridamole

- Relevance: HIGH

- As Found: Positive control

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4292

- Name: Antioxidants

- Relevance: LOW

- As Found: Unknown

- ID: M21869

- Name: Protective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M13629

- Name: Phosphodiesterase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M13865

- Name: Platelet Aggregation Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M17412

- Name: Vasodilator Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000000493

- Term: Allopurinol

- ID: D000004176

- Term: Dipyridamole

### Misc Info Module

- Version Holder: 2024-05-24
