Sodium Benzoate and/or N-Acetylcysteine Added to TAU in Patients With Early Schizophrenia Spectrum Disorder.

A Multicentre 12-week Randomised Double-blind Placebo Controlled Feasibility Trial of Sodium Benzoate and/or N-acetylcysteine Added to TAU in Patients With Early Schizophrenia Spectrum Disorder.

This study aims to determine if the addition of Sodium Benzoate and / or NAC to TAU will be acceptable and tolerable and result in overall improvement of symptoms, social and cognitive functioning in patients with early schizophrenia spectrum disorder.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorders
• Intervention / Treatment: Drug: Placebo; Drug: Sodium Benzoate; Drug: N-Acetylcysteine; Drug: Sodium Benzoate Plus N-Acetylcysteine

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Pakistan
  • Balochistan
    • Quetta, Balochistan, Pakistan
      • Balochistan Institute of Behavioral Science
  • Islamabad
    • Rawalpindi, Islamabad, Pakistan
      • Institute of Psychiatry, Rawalpindi
  • Sindh
    • Karachi, Sindh, Pakistan
      • Abbasi Shaheed Hsopital
    • Karachi, Sindh, Pakistan
      • Civil Hospital Karachi
    • Karachi, Sindh, Pakistan
      • Karwan e hayat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male/Female patients aged between 18-35 years.
2. Diagnosis of schizophrenia confirmed by SCID interview meeting DSM-V criteria for schizophrenia, schizophreniform or schizoaffective psychosis.
3. Stable on medication for the past four weeks
4. In contact with mental health services
5. Within 5 years of diagnosis of psychotic illness
6. Able to demonstrate the capacity to provide informed consent as assessed by their own clinician
7. Able to complete the required evaluations and take oral medication.
8. Effective contraceptive precautions (either the use of barrier methods or the oral contraceptive pill) to be taken by women of child-bearing age. A negative pregnancy test will be required in order to meet inclusion criteria.

Exclusion Criteria:

1. Prior history of intolerance or serious side effects to Sodium Benzoate or N-acetylcystine.
2. Concomitant use of Ascorbic acid
3. Active substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-V criteria.
4. Relevant CNS or other medical disorders.
5. Pregnant or breast feeding
6. Diagnosis of Moderate to Severe Learning Disability
7. Relevant current or past haematological, hepatic, renal, neurological or other medical disorder in the opinion of the principal investigator (PI) or the responsible clinician, that may interfere with the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium Benzoate; Sodium Benzoate added to TAU will be administered at 1000mg daily	Drug: Sodium Benzoate; Sodium Benzoate will be administered at 1000mg daily
Active Comparator: N-Acetylcysteine; N-Acetylcysteine added to TAU 1000 mgs twice daily dose	Drug: N-Acetylcysteine; N-Acetylcysteine 1000 mgs twice daily dose
Active Comparator: Placebo; Placebo added to TAU	Drug: Placebo; Placebo added to TAU
Active Comparator: Sodium Benzoate Plus N-Acetylcysteine; Sodium Benzoate will be administered at 1000mg daily and NAC 1000 mgs twice daily dose	Drug: Sodium Benzoate Plus N-Acetylcysteine; Sodium Benzoate will be administered at 1000mg daily and NAC 1000 mgs twice daily dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of intervention ( including recruitment rates and drop outs)	Feasibility estimates of delivering the intervention including recruitment rates and drop outs	Recruitment within 12 months of study start start date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall improvement in symptoms using the Positive and Negative Syndrome Scale (PANSS) total score	The PANSS is measured on a 7-point scale, and is a 30-item structured clinical interview assessing symptom severity over the previous week. The PANSS scale has a maximum score of 210 and a minimum of 30. Higher scores indicate higher severity of illness.	change in scores from Baseline to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in positive and/or negative symptoms subscales measured using the PANSS.	The PANSS is measured on a 7-point scale, and is a 30-item structured clinical interview assessing symptom severity over the previous week. The PANSS scale has a maximum score of 210 and a minimum of 30. Higher scores indicate higher severity of illness.	change in scores from Baseline to 12 weeks
Improvement on Clinical Global Impression (CGI) Scale and Social and Occupational Functioning Assessment (SOFA) scales.	Clinical Global Impression (CGI) Scale is an observer rated clinical severity measure. The minimum score is 1 and maximum 7. Higher scores indicate severity of illness. Social and Occupational Functioning Assessment (SOFA) scale is a measure of current functioning, with scores ranging from 0 to 100. Higher scores represent higher functioning	change in scores from Baseline to 12 weeks
Improvement in cognitive functioning as measured using CogState Schizophrenia Battery.		change in scores from Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Pakistan Institute of Living and Learning
• Investigators: Principal Investigator: Imran B Chaudhry, MD, Ziauddin Hospital

Publications and helpful links

General Publications

• Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008 Sep 1;64(5):361-8. doi: 10.1016/j.biopsych.2008.03.004. Epub 2008 Apr 23.
• Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P, Dursun S, Dunn G, Deakin B. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol. 2012 Sep;26(9):1185-93. doi: 10.1177/0269881112444941. Epub 2012 Apr 23.
• Chaudhry IB, Husain N, Drake R, Dunn G, Husain MO, Kazmi A, Hamirani MM, Rahman R, Stirling J, Deakin W. Add-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: pilot study. Ther Adv Psychopharmacol. 2014 Jun;4(3):110-6. doi: 10.1177/2045125313511487.
• Farokhnia M, Azarkolah A, Adinehfar F, Khodaie-Ardakani MR, Hosseini SM, Yekehtaz H, Tabrizi M, Rezaei F, Salehi B, Sadeghi SM, Moghadam M, Gharibi F, Mirshafiee O, Akhondzadeh S. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2013 Nov-Dec;36(6):185-92. doi: 10.1097/WNF.0000000000000001.
• Lane HY, Lin CH, Green MF, Hellemann G, Huang CC, Chen PW, Tun R, Chang YC, Tsai GE. Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. JAMA Psychiatry. 2013 Dec;70(12):1267-75. doi: 10.1001/jamapsychiatry.2013.2159.
• Lin CH, Lin CH, Chang YC, Huang YJ, Chen PW, Yang HT, Lane HY. Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial. Biol Psychiatry. 2018 Sep 15;84(6):422-432. doi: 10.1016/j.biopsych.2017.12.006. Epub 2017 Dec 26.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): December 30, 2020
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: April 4, 2018
• First Submitted That Met QC Criteria: April 26, 2018
• First Posted (Actual): April 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; Schizophrenia; N-Acetylcysteine; NMDA receptor; Anti-oxidant; Psychopharmacology; Sodium Benzoate
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antifungal Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine; Sodium Benzoate
• Other Study ID Numbers: PILL-Sodium Benzoate & NAC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No