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

Schizophrenia; Negative Type Clinical Trial

— NOBLE-TMS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06351514
• Other study ID #: 2023/00745
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2024
• Est. completion date: September 2026

Study information

• Verified date: April 2024
• Source: Institute of Mental Health, Singapore
• Contact: Xiaowei Tan
• Phone: 6389 2000
• Email: Xiaowei_TAN[@]imh.com.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 2026
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia
• Schizophrenia; Negative Type

Intervention

Device:
• Accelerated iTBS
Patients will be assigned to receive iTBS over the left dorsolateral prefrontal cortex or Frontal Medea with 5 sessions a day, every weekday for 1 week and total of 25 sessions. Each iTBS session is approximately 10 minutes (depth corrected Resting Motor Threshold of 100%, 60 cycles of 10 bursts of three pulses at 50 Hz, repeated at 5 Hz; 2s on and 8s off; 1800 pulses per session; with a 50-minute interval between sessions. All TBS sessions will be performed by staff trained and credentialed in TMS according to Singapore College of Psychiatrists guidelines.

Locations

Country	Name	City	State
Singapore	Institute of Mental Health	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Mental Health, Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of Negative symptoms	Assessed by PANSS, Negative symptoms subscale	Before treatment till Immediately post treatment.
Secondary	Trend of Negative symptoms	Assessed by PANSS, Negative symptoms subscale	Before treatment till Immediately post treatment, 1 Month Post Treatment & 3 Month Post Treatment.