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rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia (RADOVAN)

Primary Purpose

Negative Symptoms With Primary Psychotic Disorder, Schizophrenia

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
high-frequency rTMS
TBS
placebo
Sponsored by
University of Regensburg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Negative Symptoms With Primary Psychotic Disorder

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • ICD-10: schizophrenia with primarily negative symptoms
  • Age: 18-75 years
  • at least 35 Points at the composite score of the SANS
  • stabe medication during the last 2 weeks (at the investigator's discretion)
  • written informed consent (by the patient or guardian)

Exclusion Criteria:

  • clinically relevant unstable concomitant somatic diseases
  • previous treatment by rTMS
  • conditions in which TMS may not be applicated, as e.g., cardiac pacemakers or ferromagnetic implants
  • history of epileptic seizures
  • current substance or alcohol abuse, or clinically relevant comorbidity (according to M.I.N.I. interview)
  • unacceptable concomitant medication (benzodiazepines in higher doses, e.g., Lorazepam > 2 mg/d, Diazepam > 10 mg/d)
  • insufficient knowledge of the language of the country of the treatment site
  • pregnancy and nursing period
  • current statutory hospitalisation

Sites / Locations

  • Brno University HospitalRecruiting
  • University Hospital OstravaRecruiting
  • University Hospital Aachen
  • University of RegensburgRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

high-frequency repetitive transcranial magnetic stimulation

theta burst stimulation

sham rTMS

Arm Description

repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex using 3000 pulses applied with 10Hz and 120% resting motor threshold

intermittent theta burst stimulation over left dorsolateral prefrontal cortex using 600 pulses applied in trains of 10 triplets/bursts (50Hz) with 8s intertrain-interval and 120% resting motor threshold

half of the patients with high-frequency repetitive transcranial magnetic stimulation and half of the patients with theta burst Stimulation with angled coil (45 degree) or sham coil

Outcomes

Primary Outcome Measures

Scale for the Assessement of Negative Symptoms (SANS)
negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms

Secondary Outcome Measures

Scale for the Assessement of Negative Symptoms (SANS)
negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms
Positive and Negative syndrome scale (PANSS)
positive and negative symptoms in schizophrenia with 30 items and a range 30-210 with higher scores representing more symptoms (total score, score for positive, negative symptoms and for general psychopathology)
Calgary Depression Scale for Schizophrenia (CDSS)
Calgary Depression Scale for Schizophrenia
Clinical global impression (CGI)
measure of overall symptom severity and treatment response on a scale 1-7 with higher scores presenting more symptoms
Major Depression Inventory (MDI)
measurment of depressivity: 10 items with a range 0-50 and higher values indicating higher scores
Hamilton depression rating scale (HDRS)
measurment of depressivity: 21 items with a range 0-65 and higher values indicating higher scores
Memory span test (digit span)
test for short-term and working memory
test of attention (d2)
test of attention for measurement of concentration
Resting state electroencephalogram (EEG)
measurement of resting state electrophysiologic activity as indicated by frequency analysis and rTMS-evoked activity
magnetic resonance imaging (MRI)
structural, anatomical, diffusion weighted magnetic resonance imaging
cigarettes
number of smoked cigarettes per week

Full Information

First Posted
March 16, 2020
Last Updated
December 8, 2022
Sponsor
University of Regensburg
Collaborators
University Hospital, Aachen, University Hospital Ostrava, Brno University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04318977
Brief Title
rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia
Acronym
RADOVAN
Official Title
rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Regensburg
Collaborators
University Hospital, Aachen, University Hospital Ostrava, Brno University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Treatment of depression with repetitive transcranial magnetic stimulation (rTMS) has shown high evidence using high-frequency left dorsolateral prefrontal cortex (DLPFC) stimulation. The treatment of negative symptoms with the same protocol in schizophrenia is considered as possible effective. Theta burst stimulation is a new protocol which is characterized by shorter sessions showing first evidence that it's efficacy is comparable to the high-frequency rTMS. In this randomized placebo-controlled study the efficacy of high-frequency rTMS and TBS are evaluated.
Detailed Description
In this randomized placebo-controlled study the efficacy of high-frequency rTMS and TBS are evaluated. The active study arms are high-frequency rTMS and iTBS of the left dorsolateral prefrontal cortex to treat negative symptoms in schizophrenia. The control arm will include the same number of patients as each active arm and includes both sham rTMS and sham iTBS in the same proportion as the active treatments. Standards of the trial will be harmonized across four clinical centers with the aim to pool data for analysis. Each center is responsible for ethical approval and adherence to good clinical practice by itself (Sponsor).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Negative Symptoms With Primary Psychotic Disorder, Schizophrenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
randomized controlled trial with two active and one placebo arm
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
high-frequency repetitive transcranial magnetic stimulation
Arm Type
Experimental
Arm Description
repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex using 3000 pulses applied with 10Hz and 120% resting motor threshold
Arm Title
theta burst stimulation
Arm Type
Experimental
Arm Description
intermittent theta burst stimulation over left dorsolateral prefrontal cortex using 600 pulses applied in trains of 10 triplets/bursts (50Hz) with 8s intertrain-interval and 120% resting motor threshold
Arm Title
sham rTMS
Arm Type
Placebo Comparator
Arm Description
half of the patients with high-frequency repetitive transcranial magnetic stimulation and half of the patients with theta burst Stimulation with angled coil (45 degree) or sham coil
Intervention Type
Device
Intervention Name(s)
high-frequency rTMS
Intervention Description
repetitive transcranial magnetic stimulation
Intervention Type
Device
Intervention Name(s)
TBS
Intervention Description
theta burst stimulation
Intervention Type
Device
Intervention Name(s)
placebo
Intervention Description
placebo transcranial magnetic stimulation
Primary Outcome Measure Information:
Title
Scale for the Assessement of Negative Symptoms (SANS)
Description
negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Scale for the Assessement of Negative Symptoms (SANS)
Description
negative symptoms in schizophrenia with 25 items and a range 0-125 with higher score representing more symptoms
Time Frame
2 weeks, 4 weeks, 12 weeks
Title
Positive and Negative syndrome scale (PANSS)
Description
positive and negative symptoms in schizophrenia with 30 items and a range 30-210 with higher scores representing more symptoms (total score, score for positive, negative symptoms and for general psychopathology)
Time Frame
2 weeks, 4 weeks, 12 weeks
Title
Calgary Depression Scale for Schizophrenia (CDSS)
Description
Calgary Depression Scale for Schizophrenia
Time Frame
2 weeks, 4 weeks, 12 weeks
Title
Clinical global impression (CGI)
Description
measure of overall symptom severity and treatment response on a scale 1-7 with higher scores presenting more symptoms
Time Frame
2 weeks, 4 weeks, 12 weeks
Title
Major Depression Inventory (MDI)
Description
measurment of depressivity: 10 items with a range 0-50 and higher values indicating higher scores
Time Frame
2 weeks, 4 weeks, 12 weeks
Title
Hamilton depression rating scale (HDRS)
Description
measurment of depressivity: 21 items with a range 0-65 and higher values indicating higher scores
Time Frame
2 weeks, 4 weeks, 12 weeks
Title
Memory span test (digit span)
Description
test for short-term and working memory
Time Frame
4 weeks, 12 weeks
Title
test of attention (d2)
Description
test of attention for measurement of concentration
Time Frame
4 weeks, 12 weeks
Title
Resting state electroencephalogram (EEG)
Description
measurement of resting state electrophysiologic activity as indicated by frequency analysis and rTMS-evoked activity
Time Frame
4 weeks
Title
magnetic resonance imaging (MRI)
Description
structural, anatomical, diffusion weighted magnetic resonance imaging
Time Frame
4 weeks
Title
cigarettes
Description
number of smoked cigarettes per week
Time Frame
4 weeks, 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ICD-10: schizophrenia with primarily negative symptoms Age: 18-75 years at least 35 Points at the composite score of the SANS stabe medication during the last 2 weeks (at the investigator's discretion) written informed consent (by the patient or guardian) Exclusion Criteria: clinically relevant unstable concomitant somatic diseases previous treatment by rTMS conditions in which TMS may not be applicated, as e.g., cardiac pacemakers or ferromagnetic implants history of epileptic seizures current substance or alcohol abuse, or clinically relevant comorbidity (according to M.I.N.I. interview) unacceptable concomitant medication (benzodiazepines in higher doses, e.g., Lorazepam > 2 mg/d, Diazepam > 10 mg/d) insufficient knowledge of the language of the country of the treatment site pregnancy and nursing period current statutory hospitalisation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tobias Hebel, MD
Phone
+49-941-941-1250
Email
tobias.hebel@medbo.de
First Name & Middle Initial & Last Name or Official Title & Degree
Martin Schecklmann, PhD
Phone
+49-941-941-1250
Email
martin.schecklmann@medbo.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Berthold Langguth, MD, PhD
Organizational Affiliation
University of Regensburg
Official's Role
Study Chair
Facility Information:
Facility Name
Brno University Hospital
City
Brno
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Libor Ustohal
Facility Name
University Hospital Ostrava
City
Ostrava
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tomas Skront
Facility Name
University Hospital Aachen
City
Aachen
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Timm Pöppl
Facility Name
University of Regensburg
City
Regensburg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Hebel, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35128142
Citation
Hebel T, Langguth B, Schecklmann M, Schoisswohl S, Staudinger S, Schiller A, Ustohal L, Sverak T, Horky M, Kasparek T, Skront T, Hyza M, Poeppl TB, Riester ML, Schwemmer L, Zimmermann S, Sakreida K. Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN). Contemp Clin Trials Commun. 2022 Jan 20;26:100891. doi: 10.1016/j.conctc.2022.100891. eCollection 2022 Apr.
Results Reference
derived

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rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia

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