L-arginine in Treatment as Usual in Schizophrenia

NCT ID: NCT00718510

Last Updated: 2017-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2012-10-31

Brief Summary

STUDY OBJECTIVES: To determine whether the addition of L-arginine to treatment as usual (TAU) in schizophrenia further improves and enhances therapeutic efficacy (positive, negative and depressive symptoms) and effectiveness of antipsychotic treatment

STUDY POPULATION: Patients diagnosed (DSM-IV criteria) with schizophrenia or schizoaffective disorder

Total expected number of patients: 14

INVESTIGATIONAL COMPOUND: L-arginine capsules, 3 grams of L-arginine given twice a day (total daily dose of 6 grams/day)

DURATION OF ACTIVE TREATMENT: 3 weeks followed by wash-out phase of 5 days and 3 weeks of second treatment phase (cross-over design)

EVALUATION CRITERIA: Primary (efficacy) outcomes: PANSS scores. Secondary outcomes: Calgary Depression Scale for schizophrenia, CGI; AIMS, UKU-assessment of side-effects

ASSESSMENT SCHEDULE: Treatment arm 1: Baseline, weeks: 1,2,3, wash-out phase; week 4, cross-over phase: treatment phase-2; weeks 5,6,7

STATISTICAL CONSIDERATIONS: Analysis of variance of outcome measures with treatment as the between-subject factor and pre- and post-treatment scores as within- subjects factors.

DURATION OF STUDY PERIOD: Patient recruitment to be completed in 12 months, study full completion 18 months.

Detailed Description

In the current study, our goals were to examine the clinical benefits of the nitric oxide (NO) donor and main precursor of NO, L-arginine, to further improve the symptoms of schizophrenia with minimum or no additional side-effects. L-Arginine is classified as a semi-essential or conditionally essential amino acid depending on the developmental stage and health status of the individual. Glutamate N-methyl-D-aspartate (NMDA) receptors have functional connections to the NO system in the brain. Dysfunction of connectivity of the neuroregulators glutamate and NO have been implicated in mechanisms of psychosis. Therefore, any downstream effects of NMDA dysfunction in schizophrenia may be ultimately mediated by the NO system at a cellular level. As an augmenting treatment to antipsychotic therapy, we examined the ability of L-arginine to further improve residual symptoms in the illness.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

L-arginine first/placebo second

Patients with diagnosis of schizophrenia will be randomised to receive L-arginine first/placebo second 3 grams bid (cross-over design) in addition to treatment as usual. The active treatment period will be 3 weeks, with a wash-out period of 5 days and re-commencing on the alternative arm of the randomization

Group Type: ACTIVE_COMPARATOR

L-Arginine

Intervention Type: DRUG

3 grams, twice daily, oral administration

Placebo first/L-arginine second

Patients with diagnosis of schizophrenia will be randomised to receive placebo first/L-arginine second 3 grams bid (cross-over design) in addition to treatment as usual. The active treatment period will be 3 weeks, with a wash-out period of 5 days and re-commencing on the alternative arm of the randomization

Group Type: PLACEBO_COMPARATOR

L-Arginine

Intervention Type: DRUG

3 grams, twice daily, oral administration

Interventions

L-Arginine

3 grams, twice daily, oral administration

Intervention Type: DRUG

Other Intervention Names

Placebo

Eligibility Criteria

Inclusion Criteria

1. Aged 18-65 years

2. Diagnoses of schizophrenia or schizoaffective disorder using the Diagnostic and Statistical Manual-IV (DSM-IV) criteria

3. Competent and willing to give informed consent

4. Able to take oral medication and likely to complete the required evaluations.

5. Medication remained stable 4 weeks prior to baseline.

6. Female participants of child bearing capability must be willing to use adequate contraceptives (4.6.1a) for the duration of the study, and, willing to have a pregnancy test pretreatment and during the study.

Adequate contraception is defined as use of contraceptive double barrier system (i.e. condom and spermicide) or contraceptive implant, oral contraceptive or injected depot contraceptive plus other form of contraceptive, i.e. condom. Females will be considered incapable of child bearing if they are one year postmenopausal or irreversibly surgically sterilised.

Exclusion Criteria

1. Relevant medical illness will be determined in the first instance by asking the patients mental health care team if the patient has any medical condition/problems. After consent has been obtained, the research nurse/research doctor will then have access to the patient's notes and if necessary communicate with his/her GP and will assess patient eligibility to take part in the clinical trial by scrutinising the patient's past medical history, most recent blood results, electrocardiograms, as well as any physical tests that have been performed on the patient. If there are any deviations from the 'norm' the investigators will assess the eligibility of the individual patient.

2. Patients receiving active treatments for Herpes virus as L-arginine may counteract the benefits of lysine to treat herpes virus

3. Patients who are currently receiving NSAIDs or other drugs that can cause significant stomach an gastrointestinal side-effects

4. Drugs that alter potassium levels in the body, such as ACE inhibitors and potassium sparing diuretics

5. Patients who are pregnant or plan to become pregnant while using this amino acid

6. Patients who are breastfeeding

7. Prior history of intolerance to L-arginine

8. Any significant change of psychotropic medications done within the previous 4 weeks

9. Diagnosis of substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-IV criteria

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alberta Health services

OTHER

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Serdar Dursun

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Serdar Dursun, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Glen Baker, Ph.D., D.Sc.

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

John C. Lind, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Alberta Hospital Edmonton

Phil Tibbo, F.R.C.P.C.

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Mee-Sook Song, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Pierre Flor-Henry, F.R.C.P.C.

Role: PRINCIPAL_INVESTIGATOR

Alberta Hospital Edmonton

Diane Cox, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

Alberta Hospital Edmonton

Edmonton, Alberta, Canada

Countries

Canada

Other Identifiers

CPAT7176

Identifier Type: -

Identifier Source: org_study_id