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

NCT03510741 | Completed Phase 2 DMC

• 1 other identifier: PILL-Sodium Benzoate & NAC-001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Schizophrenia; Schizophreniform Disorders; Schizoaffective Disorder

Keywords

Schizophrenia; Sodium Benzoate; N-Acetylcysteine; NMDA receptor; Psychopharmacology; Anti-oxidant; Inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Overall improvement in symptoms using the Positive and Negative Syndrome Scale (PANSS) total score

  change in scores from Baseline to 12 weeks

Other Outcomes (3)

• Improvement in positive and/or negative symptoms subscales measured using the PANSS.

  change in scores from Baseline to 12 weeks

• Improvement on Clinical Global Impression (CGI) Scale and Social and Occupational Functioning Assessment (SOFA) scales.

  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

Study Arms (4)

Sodium Benzoate

ACTIVE COMPARATOR

Sodium Benzoate added to TAU will be administered at 1000mg daily

Drug: Sodium Benzoate

N-Acetylcysteine

ACTIVE COMPARATOR

N-Acetylcysteine added to TAU 1000 mgs twice daily dose

Drug: N-Acetylcysteine

Placebo

ACTIVE COMPARATOR

Placebo added to TAU

Drug: Placebo

Sodium Benzoate Plus N-Acetylcysteine

ACTIVE COMPARATOR

Sodium Benzoate will be administered at 1000mg daily and NAC 1000 mgs twice daily dose

Drug: Sodium Benzoate Plus N-Acetylcysteine

Interventions

Sodium Benzoate DRUG

Sodium Benzoate will be administered at 1000mg daily

Sodium Benzoate

N-Acetylcysteine DRUG

N-Acetylcysteine 1000 mgs twice daily dose

N-Acetylcysteine

Placebo DRUG

Placebo added to TAU

Placebo

Sodium Benzoate Plus N-Acetylcysteine DRUG

Sodium Benzoate will be administered at 1000mg daily and NAC 1000 mgs twice daily dose

Sodium Benzoate Plus N-Acetylcysteine

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male/Female patients aged between 18-35 years.
• Diagnosis of schizophrenia confirmed by SCID interview meeting DSM-V criteria for schizophrenia, schizophreniform or schizoaffective psychosis.
• Stable on medication for the past four weeks
• In contact with mental health services
• Within 5 years of diagnosis of psychotic illness
• Able to demonstrate the capacity to provide informed consent as assessed by their own clinician
• Able to complete the required evaluations and take oral medication.

You may not qualify if:

• Prior history of intolerance or serious side effects to Sodium Benzoate or N-acetylcystine.
• Concomitant use of Ascorbic acid
• Active substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-V criteria.
• Relevant CNS or other medical disorders.
• Pregnant or breast feeding
• Diagnosis of Moderate to Severe Learning Disability
• 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.

Sponsors & Collaborators

• Pakistan Institute of Living and Learning: lead

Study Sites (5)

Balochistan Institute of Behavioral Science

Quetta, Balochistan, Pakistan

Location

Institute of Psychiatry, Rawalpindi

Rawalpindi, Islamabad, Pakistan

Location

Abbasi Shaheed Hsopital

Karachi, Sindh, Pakistan

Location

Civil Hospital Karachi

Karachi, Sindh, Pakistan

Location

Karwan e Hayat

Karachi, Sindh, Pakistan

Location

Related Publications (7)

• 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.

  PMID: 18436195 BACKGROUND

• 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.

  PMID: 25057343 BACKGROUND

• 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.

  PMID: 24201233 BACKGROUND

• 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.

  PMID: 24089054 BACKGROUND

• 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.

  PMID: 29397899 BACKGROUND

• 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.

  PMID: 22526685 BACKGROUND

• Husain MO, Chaudhry IB, Khoso AB, Husain MI, Ansari MA, Mehmood N, Naqvi HA, Nizami AT, Talib U, Rajput AH, Bassett P, Foussias G, Deakin B, Husain N. Add-on Sodium Benzoate and N-Acetylcysteine in Patients With Early Schizophrenia Spectrum Disorder: A Multicenter, Double-Blind, Randomized Placebo-Controlled Feasibility Trial. Schizophr Bull Open. 2024 Feb 9;5(1):sgae004. doi: 10.1093/schizbullopen/sgae004. eCollection 2024 Jan.

  PMID: 39144112 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Inflammation

Interventions

Sodium Benzoate; Acetylcysteine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzoic Acid; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Imran B Chaudhry, MD

  Ziauddin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind placebo controlled trial
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a 2x2 factorial design trial

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: April 27, 2018
• Study Start: January 1, 2019
• Primary Completion: December 30, 2020
• Study Completion: March 30, 2021
• Last Updated: April 27, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

PA (5)