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

Schizophrenia Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03510741
• Other study ID #: PILL-Sodium Benzoate & NAC-001
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2019
• Est. completion date: March 30, 2021

Study information

• Verified date: April 2022
• Source: Pakistan Institute of Living and Learning
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: March 30, 2021
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• Disease
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia
• Schizophreniform Disorders

Intervention

Drug:
• Sodium Benzoate
Sodium Benzoate will be administered at 1000mg daily
• N-Acetylcysteine
N-Acetylcysteine 1000 mgs twice daily dose
• Placebo
Placebo added to TAU
• Sodium Benzoate Plus N-Acetylcysteine
Sodium Benzoate will be administered at 1000mg daily and NAC 1000 mgs twice daily dose

Locations

Country	Name	City	State
Pakistan	Abbasi Shaheed Hsopital	Karachi	Sindh
Pakistan	Civil Hospital Karachi	Karachi	Sindh
Pakistan	Karwan e Hayat	Karachi	Sindh
Pakistan	Balochistan Institute of Behavioral Science	Quetta	Balochistan
Pakistan	Institute of Psychiatry, Rawalpindi	Rawalpindi	Islamabad

Sponsors (1)

Lead Sponsor	Collaborator
Pakistan Institute of Living and Learning

Country where clinical trial is conducted

Pakistan, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Improvement in cognitive functioning as measured using CogState Schizophrenia Battery.		change in scores from Baseline to 12 weeks
Primary	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	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