An Open-Label, Single Arm Study of the Efficacy of Accelerated Intermittent Theta Burst Stimulation in Schizophrenia Patients With Persistent Negative Symptoms (NOBLE-TMS)

Schizophrenia patients commonly present with persistent negative symptoms which remain the main reason for dysfunction after recovery from an acute episode of psychotic symptoms. Negative symptoms in schizophrenia exact significant burden with no effective pharmacological or behavior treatment options thus far. Neuromodulatory modalities present a novel and alternative treatment approach and recent trials have shown preliminary evidence for the efficacy of intermittent Theta Burst Stimulation (iTBS) to treat negative symptoms in schizophrenia. In this study, we aim to examine the effectiveness of an accelerated iTBS treatment protocol as an augmentation treatment regime for patient in rehabilitation care with persistent negative symptoms.

We propose a pragmatic, open label and single arm clinical trial. Forty patients with diagnosis of schizophrenia, who had been stabilized from psychotic symptoms and currently suffering from dominant negative symptoms will be recruited and undergo accelerated iTBS treatment for 5 consecutive sessions each day for 5 working days. Participants will be followed up immediately, 1 month and 3 months after the end of treatment. Clinical assessment includes, BNSS, The Brief Negative Symptom Scale; SANS, Scale for the assessment of negative symptoms; SAPS, Scale for the assessment of positive symptoms; PANSS, Positive and Negative Symptoms Scale; MoCA, Montreal Cognitive Assessment scale; CDSS, Calgary Depression Scale for Schizophrenia: SDS, Sheehans' disability scale and EQ-5D. The primary endpoint of the trial is the change of negative symptoms as assessed by PANSS, negative symptoms subscale immediately after the treatment.

This study will determine whether accelerated iTBS is effective to be delivered as an augmentation therapy for patients with persistent negative symptoms. The optimal treatment system for this population can be immediately translated to clinical practice and benefit patients in need.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Negative Type
• Intervention / Treatment: Device: Accelerated iTBS

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaowei Tan; Phone Number: 6389 2000; Email: Xiaowei_TAN@imh.com.sg
• Study Contact Backup: Name: Hasvinjit Kaur; Phone Number: 6389 2000; Email: HKG_SINGH@imh.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 539747
    • Recruiting
    • Institute of Mental Health
    • Contact: Jenny Tay; Email: jenny_am_tay@imh.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥21 and ≤65 years;
2. With primary diagnosis of schizophrenia or schizoaffective disorder;
3. Patients experienced prominent and persistent negative symptoms [Scale for the Assessment of Negative Symptoms (SANS) score ≥3 or Positive and Negative Symptoms Scale (PANSS)- negative subscale score ≥20] in past 6 months;
4. No clinically significant positive symptoms [PANSS positive subscale score <20];
5. No clinically significant depressive symptoms [Calgary Depression Scale for Schizophrenia (CDSS) score subscale <12];
6. Able to give consent.

Exclusion Criteria:

1. With current misuse of or dependence on illegal drugs or alcohol;
2. High Suicide risk;
3. History of epileptic seizures;
4. With severe brain trauma, injury or other neurological diseases;
5. Metal (implants) in the skull;
6. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Negative symptoms	Assessed by PANSS, Negative symptoms subscale	Before treatment till Immediately post treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trend of Negative symptoms	Assessed by PANSS, Negative symptoms subscale	Before treatment till Immediately post treatment, 1 Month Post Treatment & 3 Month Post Treatment.

Collaborators and Investigators

• Sponsor: Institute of Mental Health, Singapore

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 2023/00745

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Upon request, as approved by DSRB.

Drug and device information, study documents

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