TMS in Treatment of Schizophrenia Negative Symptoms

Efficacy and Safety of High-frequency Repetitive Transcranial Magnetic Stimulation With H7-coil in the Treatment of Schizophrenia Negative Symptoms; A Multicenter, Randomized, Sham Controlled, Triple Blind Trial

Primary objective: to examine the efficacy and safety of high frequency repetitive transcranial magnetic stimulation (HF rTMS) with H7-coil applied once daily during the twenty days, augmentative to the standard antipsychotic pharmacotherapy and other treatment of negative symptoms in schizophrenia.

Targeted population: patients diagnosed with schizophrenia, 18-55 years old with predominant negative symptoms, stable condition for >3 months and unchanged antipsychotic therapy for >1 months and no treatment with antidepressants.

Study design: industry independent, multicenter, prospective randomized sham-controlled, two-arms, triple-blind superiority clinical trial with concealed allocation and masked independent outcome assessment.

Primary outcome: adjusted median of differences in total SANS score. Adjustment for age, gender, baseline total SANS score, duration of the disorder, and antipsychotic therapy.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Device: HR rTMS; Device: sham

• Study Type: Interventional
• Enrollment (Anticipated): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • Recruiting
    • PB Sveti Ivan
    • Contact: Ena Ivezic, MA; Phone Number: 38513430171; Email: ena.ivezic@pbsvi.hr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Confirmation diagnosis of schizophrenia (ICD-10 F20) using the Mini-International Neuropsychiatric Interview (MINI) (Lecrubier et al., 1997; Sheehan et al., 1998),
2. Age 18-55 years,
3. Both genders,
4. PANSS negative symptoms subscale score >24,
5. PANSS positive symptoms subscale score <20,
6. Stable condition (no acute psychosis exacerbation, no psychiatric hospitalization because of relapse or worsening of symptoms) during at least three months,
7. Stable antipsychotic therapy with no change of drugs or doses during the one months before the enrollment.

Exclusion Criteria:

1. Antipsychotics dose change or change of antipsychotic drug,
2. Hospitalization for somatic illness in another institution,
3. Termination of treatment in a Psychiatric Hospital "Sveti Ivan",
4. Pregnancy,
5. Missed more than three consecutive interventions,
6. Withdrawal of consent to participate for the sake of intolerance of TMS or for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HR rTMS H7-coil intervention group	Device: HR rTMS; high frequency repetitive transcranial magnetic stimulation (HF rTMS) with H7-coil applied once daily during the twenty days
SHAM_COMPARATOR: sham control group	Device: sham; SHAM HF rTMS coil once daily x 20 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted median of differences in total SANS score	Adjusted median of differences in total SANS score (Andreasen, 1989). We will adjust the medians for age, gender, baseline total SANS score, duration of the disorder, and antipsychotic therapy	assessed up to 20 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SNS score	Change in Self-Evaluation of Negative Symptoms Scale (SNS) (Dollfus, Mach and Morello, 2016)	assessed up to 20 days of treatment
Change of BNSS score	Change in Brief Negative Symptom Scale (BNSS), (Kirkpatrick et al., 2006)	assessed up to 20 days of treatment
Change in PANSS negative symptom subscale with items rescaled to 0-6 range	Change in PANSS negative symptoms subscale with items rescaled to 0-6 range, (Kay, Fiszbein and Opler, 1987)	assessed up to 20 days of treatment
Change in CDSS score	Change in depressive symptoms measured using Calgary Depression Scale for Schizophrenia (CDSS) (Addington, Addington and Schissel, 1990)	assessed up to 20 days of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients self-reported side effects during therapy, confirmed by the medical nurse		assessed up to 20 days of treatment
Change in verbal memory	Change in verbal memory using Auditory Verbal Learning Test (AVLT), subtest from Wechsler Memory Scale (Revised)-Verbal-Logical Memory	assessed up to 20 days of treatment
Change in visual memory	Change in visual memory using Benton's visual retention test (BVRT)	assessed up to 20 days of treatment
Change in numeric memory	Change in numeric memory using subtest from Wechsler Memory Scale (Revised)-Digit Span	assessed up to 20 days of treatment
Change in visual-spatial abilities and executive function	Change in visual-spatial abilities and executive function using TMT (A/B) Trail Making Test, and subtest from Wechsler Intelligence Scale (Revised)-Block Design	assessed up to 20 days of treatment
Change in psihomotor speed	Change in psihomotor speed using subtest from Wechsler Intelligence Scale (Revised)-Digit Symbol Substitution Test	assessed up to 20 days of treatment
Change in verbal fluency	Change in verbal fluency using FAS Verbal Fluency Test	assessed up to 20 days of treatment
Change in recognition of facial expressions of emotions	Change in recognition of facial expressions of emotions using the Penn's Emotion Recognition Task test (ER40)	assessed up to 20 days of treatment

Collaborators and Investigators

• Sponsor: Sveti Ivan Psychiatric Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 4, 2019
• Primary Completion (ANTICIPATED): December 15, 2022
• Study Completion (ANTICIPATED): March 15, 2023

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (ACTUAL): February 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: TMS_negative symptoms

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