Efficacy and Mechanisms of Low-intensity Focused Ultrasound on Negative Symptoms in Patients With Schizophrenia

Based on our research background, we hypothesize that LIFUS has neuromodulation effects on brain cortex and the active LIFUS on left-DLPFC would improve negative symptoms in schizophrenia patients. It would firstly verify the safety of LIFUS on human as well. The multimodal MRI will be contributed to investigate the possible mechanism of negative symptoms.

Study Overview

• Status: Recruiting
• Conditions: Negative Symptoms of Schizophrenia
• Intervention / Treatment: Device: Low-intensity Focused Ultrasound(LIFUS)

Detailed Description

Firstly, we plan to explore the short-term effects of LIFUS on cortical excitability by detecting the MEP amplitude. 40 patients and relatively well matched healthy-control would be enrolled. After MEP detection and baseline evaluations, the two groups will be treated with one-single intervention on the primary motor cortex. The cognitive function and MEP amplitude will be assessed respectively at the moment, after 15 minutes and 30 minutes. Then, it is a randomized double-blind sham-controlled LIFUS intervention trial in schizophrenia patients. After screening and baseline evaluations, the 40 patients with schizophrenia will be treated with active LIFUS or sham stimulation for 3 weeks on the left DLPFC. The multimodal MRI will be acquired. Clinical symptoms and cognitive function will be assessed respectively at baseline, at the end of fifth treatments and after the end of the treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dengtang LIU; Phone Number: 86 18017311138; Email: erliu110@126.com
• Study Contact Backup: Name: Qiong Xiang; Phone Number: 13817369060; Email: xiangqiongxl@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center
      • Contact: Dengtang LIU; Phone Number: 18017311138; Email: erliu110@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Inclusion Criteria (patients):

  1. Meet the DSM-5 diagnostic criteria for schizophrenia or schizoaffective disorder;
  2. Age18-50, right-handed, Han nationality;
  3. the score of at least 1 item from N1 to N7 is ≥4 (moderate or above);
  4. Be in a stable condition, received second-generation antipsychotics for at least 4 weeks or more;
  5. Written informed consent;

• Exclusion Criteria (patients):

  1. Current or past neurological illness, severe physical diseases, substance abuse or alcohol dependence, mental retardation, pregnant or lactation;
  2. Uncooperative or risky patients with high excitement, stupor, disorder of words and deeds, negative suicide, etc.;
  3. A history of MECT or other physical therapy within 6 months;
  4. A history of epilepsy, or epileptic waves on the baseline EEG;
  5. Ruled out share antiepileptic drugs, carbamazepine, valproic acid salt) or larger doses of benzodiazepines drugs (> 10 mg/day, diazepam clonazepam 2 mg/day, 1 mg/day, alprazolam lorazepam 2 mg/day, midazolam 10 mg/day, 20 mg/day, Mr Shah diazepam triazolam 0.5 mg/day), avoid the use of chlorine drug, (in principle, to avoid the use of antiepileptic drugs and clonazepam;Other antipsychotic drugs, if necessary, remain unchanged during the course of treatment;
  6. Contraindications to LIFUS and MRI are present.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: LIFUS-left DLPFC; 20 patients will be treated with active LIFUS for 3 weeks on the left DLPFC.	Device: Low-intensity Focused Ultrasound(LIFUS); Patients with schizophrenia will be treated with active LIFUS or sham stimulation for 3 weeks on the left DLPFC.
Sham Comparator: LIFUS-SHAM; 20 patients will be treated with sham LIFUS for 3 weeks on the left DLPFC.	Device: Low-intensity Focused Ultrasound(LIFUS); Patients with schizophrenia will be treated with active LIFUS or sham stimulation for 3 weeks on the left DLPFC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Symptoms-PANSS	Change from baseline in Positive and Negative Syndrome Scale(PANSS)	baseline and 15 days
Clinical Symptoms-SANS	Change from baseline in the Scale for the Assessment of Negative Symptoms(SANS)	baseline and 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Function	Change from baseline in the Brief Cognition Test (C-BCT)	baseline, after the fifth treatment and 15 days
Change of brain neuroimaging	Brain structure, Resting-state fMRI data, Arterial Spin Labeling(ASL), 1H-MRS in DLPFC are acquired.	baseline, fifth treatment and 15th treatment
Cortex Excitability	MEP amplitude	baseline，the moment after the intervention, after 15 minutes and 30 minutes

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2020
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): July 31, 2022

Study Registration Dates

• First Submitted: October 15, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: August 12, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Low-intensity Focused Ultrasound; Negative Symptoms of Schizophrenia Patients
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 2020-TX-006

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