Schizophrenia and Related DisordersOCoPS-PNCT03921450
Overcoming Psychomotor Slowing in Psychosis (OCoPS-P)
A study testing 1 Hz rTMS and iTBS in people with Schizophrenia and Related Disorders and Schizophrenia, run by University of Bern at 1 site in Switzerland.
Trial summary
Psychomotor slowing is a major problem in psychosis. Aberrant function of the cerebral motor system is linked to psychomotor slowing in patients, particularly resting state hyperactivity in premotor cortices. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia and Related Disorders, Schizophrenia, Schizoaffective Disorder
- What is being tested?
- 1 Hz rTMS and iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 1 siteSwitzerland
- Study dates
- 25 Mar 2019to 10 Feb 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Right-handed subjects
- Ability and willingness to participate in the study
- Ability to provide written informed consent
- Informed Consent as documented by signature
- Schizophrenia spectrum disorder according to diagnostic and statistical manual version 5 (DSM-5) criteria with current psychomotor slowing according to the Salpetriere Retardation Rating Scale (SRRS), score >= 15
Who cannot join
- Substance abuse or dependence other than nicotine
- Past or current medical or neurological condition associated with impaired or aberrant movement, such as brain tumors, stroke, M. Parkinson, M. Huntington, dystonia, or severe head trauma with subsequent loss of consciousness.
- Epilepsy or other convulsions
- History of any hearing problems or ringing in the ears
- Standard exclusion criteria for MRI scanning and TMS; e.g. metal implants, claustrophobia
- Patients only: any TMS treatment in the past 3 months
Show all 12Show fewer
- Women who are pregnant or breast feeding,
- Intention to become pregnant during the course of the study,
- Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
- Previous enrolment into the current study,
- Enrolment of the investigator, his/her family members, employees and other dependent persons
- Controls only: history of any psychiatric disorder or first-degree relatives with schizophrenia spectrum disorders.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Overcoming Psychomotor Slowing in Psychosis (OCoPS-P): a 3-week, Randomized, Double-blind, Placebo-controlled Trial of add-on Repetitive Transcranial Magnetic Stimulation for Psychomotor Slowing in Psychosis
Psychomotor slowing is a major problem in psychosis. Aberrant function of the cerebral motor system is linked to psychomotor slowing in patients, particularly resting state hyperactivity in premotor cortices. A previous clinical trial indicated that inhibitory stimulation of the premotor cortex would reduce psychomotor slowing. The current study is further exploring this effect in a randomized, placebo-controlled, double-blind design with three arms of transcranial magnetic stimulation and measures of brain imaging and physiology prior to and after the intervention.
Read the detailed description
As psychomotor slowing is a major problem in schizophrenia, contributing to poor functional outcome, and as no current treatment is effectively targeting psychomotor slowing, this study seeks to test noninvasive brain stimulation to overcome psychomotor slowing. Previous studies documented an aberrant increase of neural activity within the supplementary motor area (SMA) in patients with schizophrenia who had psychomotor slowing. Furthermore, a pilot study in major depression and schizophrenia indicated that inhibitory 1 Hz repetitive transcranial magnetic stimulation (rTMS) would improve psychomotor slowing in 82% of the participants. While this is encouraging, further evidence is needed to 1) replicate the clinical effect of 1 Hz rTMS on the SMA in schizophrenia, 2) to test against sham stimulation, facilitatory stimulation and no intervention, and 3) to test the effects of rTMS on the neural circuitry. Therefore, OCoPS includes more patients, more treatment arms, and more outcome variables than the first pilot trial.
Here we will enroll 88 patients with schizophrenia spectrum disorders and severe psychomotor slowing according to a standard rating scale. Subjects will be randomized to four arms, three of which are double blinded.
three weeks of daily rTMS over the SMA will be delivered. The first group receives inhibitory 1 Hz rTMS, the second group receives facilitatory intermittent theta burst stimulation (iTBS), and the third group receives sham stimulation with a placebo-coil. The fourth group will have no rTMS during the first three weeks, but will repeat the baseline measures after three weeks and then enter a treatment with 1Hz rTMS for three weeks. Outcome measures include the Salpetriere Retardation Rating Scale, observer ratings of motor behavior as well as measures of functioning. After the interventions, follow-up visits are planned at week 6 and week 24.
Finally, at baseline and after the rTMS course, patients will undergo MRI scanning for structural and functional alterations of the cerebral motor system.
- Conditions
- Schizophrenia and Related Disorders, Schizophrenia, Schizoaffective Disorder, Brief Psychotic Disorder
- Being tested
- 1 Hz rTMS, iTBS, Placebo
- Keywords
- motor behavior, psychomotor slowing, psychosis
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Motor Activity, Psychomotor Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 Hz rTMSDevice
1 Hz stimulation at 110% of resting motor threshold over supplementary motor area
iTBSDevice
50 Hz theta burst stimulation at 80% of resting motor threshold over supplementary motor area
PlaceboDrug
1 Hz stimulation with the placebo TMS coil without any magnetic emission
| Study group | Role | What they receive |
|---|---|---|
| Inhibitory repetitive transcranial magnetic stimulation (rTMS) | Experimental | 1 Hz stimulation of 17 mins over the supplementary motor area (SMA), 1000 pulses at 110% resting motor threshold intensity total of 15 sessions in 3 weeks Receives: Device: 1 Hz rTMS |
| Facilitatory intermittent theta burst stimulation (iTBS) | Active comparator | Intermittent theta burst stimulation of 50 Hz over the supplementary motor area (SMA) with 600 pulses in 2 sec trains every 10 seconds for 190 seconds total. Two iTBS stimulations will be administered with 15 mins pause in between.
total of 15 sessions in 3 weeks Receives: Device: iTBS |
| Placebo | Placebo comparator | 1 Hz stimulation of 17 mins over the supplementary motor area (SMA) without any magnetic emission using a placebo-coil that looks identical and makes identical sounds as the real TMS coil total of 15 sessions in 3 weeks Receives: Drug: Placebo |
| Waiting group | No intervention | This group will receive no intervention for 3 weeks. Afterwards they will receive the inhibitory rTMS protocol as in the first arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of responders at week 3
Proportion of participants with >30% reduction from baseline in the Salpetriere Retardation Rating Scale (SRRS)
Measured: Week 3
Change in Salpetriere Retardation Rating Scale (SSRS) from baseline
Change in the Salpetriere Retardation Rating Scale (SRRS) from baseline; the total score of 15 items is used, ranging 0-60 with higher scores indicating worse outcome
Measured: Week 3, week 6, week 24
Secondary outcomes (11)
Change in catatonia severity from baseline to week 3
Observer based rating of catatonia severity with the Bush Francis Catatonia Rating Scale (BFCRS), assessment blind to intervention, total score of the BFCRS is used ranging 0-69 , with higher scores indicating poorer outcome
Measured: Week 3, week 6, week 24
Change in negative symptoms from baseline
Change in the Brief Negative Symptom Scale (BNSS) from baseline, total score is used, ranging from 0-78 with higher values indicating poorer outcome, i.e. more negative symptom severity
Measured: Week 3, week 6, week 24
Change in psychosis severity from baseline
Change in the Positive And Negative Symptom Scale (PANSS) from baseline, PANSS total score assesses the severity of positive, negative and general symptoms, ranging from 30-210 with higher scores indicating increased symptom severity, i.e. poorer outcome
Measured: Week 3, week 6, week 24
Change in physical activity self report from baseline
Change in the International Physical Activity Questionnaire (IPAQ), the total score is used ranging from 0-70000 metabolic equivalent (MET)
Measured: Week 3, week 6, week 24
Change in objectively measured physical activity from baseline
Change in the activity levels using wrist actigraphy
Measured: Week 3, week 6, week 24
Change in dexterity from baseline
Change in the coin rotation task from baseline
Measured: Week 3, week 6, week 24
Change in cortical excitability of the motor cortex from baseline
Change in Short Interval Cortical Inhibition (SICI) from baseline
Measured: Week 3, week 6, week 24
Change in social and community functioning
Change in Social and Occupational Functional Assesment Scale (SOFAS) from baseline, the score ranges from 0-100 with higher scores indicating better functioning, i.e. better outcome
Measured: Week 3, week 6, week 24
Change in functional capacity
Change in the Score of the brief version of the University of California, San Diego, Performance-Based Skills Assessment (UPSA-brief) assessment from baseline, higher scores indicating better function, the total score is used ranging 0-100
Measured: Week 3, week 6, week 24
Change in functional connectivity
Change in the resting state functional connectivity within the cerebral motor system based on functional magnetic resonance imaging scans from baseline
Measured: Week 3
Change in resting state cerebral perfusion
Change in the resting state cerebral perfusion within the cerebral motor system based on functional magnetic resonance imaging scans from baseline
Measured: Week 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2019
- Study start25 Mar 2019
- Primary completion1 Nov 2022
- Study completion10 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Schizophrenia and Related DisordersStudies of the same condition, open and under way.
- More trials run by University of BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 3 week intervention with 15 sessions of add-on rTMS in 4 parallel arms, randomized, double-blind, placebo-controlled
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sebastian Walther, MD, Principal investigator, University of Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03921450
- Sponsor's protocol ID
- 2018-02164
- Other IDs
- 2018
- Acronym
- OCoPS-P
- Status last verified
- Feb 2023
- First submitted
- 16 Apr 2019
- Last updated
- 14 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Walther S, Alexaki D, Weiss F, Baumann-Gama D, Kyrou A, Nuoffer MG, Wuthrich F, Lefebvre S, Nadesalingam N. Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation: A Randomized Clinical Trial. JAMA Psychiatry. 2024 Jun 1;81(6):563-571. doi: 10.1001/jamapsychiatry.2024.0026.
PubMed 38416468
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Overcoming Psychomotor Slowing in Psychosis (OCoPS-P): a 3-week, Randomized, Double-blind, Placebo-controlled Trial of add-on Repetitive Transcranial Magnetic Stimulation for Psychomotor Slowing in Psychosis
- ClinicalTrials.gov ID
- NCT03921450
- Acronym / sponsor ID
- OCoPS-P / 2018-02164
- Conditions
- Schizophrenia and Related Disorders, Schizophrenia, Schizoaffective Disorder, Brief Psychotic Disorder
- Keywords
- motor behavior, psychomotor slowing, psychosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- University of BernUniversity, hospital or other
- Study start
- 25 Mar 2019 (actual)
- Primary completion
- 1 Nov 2022 (actual)
- Study completion
- 10 Feb 2023 (actual)
- First posted
- 19 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Psychomotor slowing is a major problem in psychosis. Aberrant function of the cerebral motor system is linked to psychomotor slowing in patients, particularly resting state hyperactivity in premotor cortices. A previous clinical trial indicated that inhibitory stimulation of the premotor cortex would reduce psychomotor slowing. The current study is further exploring this effect in a randomized, placebo-controlled, double-blind design with three arms of transcranial magnetic stimulation and measures of brain imaging and physiology prior to and after the intervention.
Detailed description
As psychomotor slowing is a major problem in schizophrenia, contributing to poor functional outcome, and as no current treatment is effectively targeting psychomotor slowing, this study seeks to test noninvasive brain stimulation to overcome psychomotor slowing. Previous studies documented an aberrant increase of neural activity within the supplementary motor area (SMA) in patients with schizophrenia who had psychomotor slowing. Furthermore, a pilot study in major depression and schizophrenia indicated that inhibitory 1 Hz repetitive transcranial magnetic stimulation (rTMS) would improve psychomotor slowing in 82% of the participants. While this is encouraging, further evidence is needed to 1) replicate the clinical effect of 1 Hz rTMS on the SMA in schizophrenia, 2) to test against sham stimulation, facilitatory stimulation and no intervention, and 3) to test the effects of rTMS on the neural circuitry. Therefore, OCoPS includes more patients, more treatment arms, and more outcome variables than the first pilot trial.
Here we will enroll 88 patients with schizophrenia spectrum disorders and severe psychomotor slowing according to a standard rating scale. Subjects will be randomized to four arms, three of which are double blinded.
three weeks of daily rTMS over the SMA will be delivered. The first group receives inhibitory 1 Hz rTMS, the second group receives facilitatory intermittent theta burst stimulation (iTBS), and the third group receives sham stimulation with a placebo-coil. The fourth group will have no rTMS during the first three weeks, but will repeat the baseline measures after three weeks and then enter a treatment with 1Hz rTMS for three weeks. Outcome measures include the Salpetriere Retardation Rating Scale, observer ratings of motor behavior as well as measures of functioning. After the interventions, follow-up visits are planned at week 6 and week 24.
Finally, at baseline and after the rTMS course, patients will undergo MRI scanning for structural and functional alterations of the cerebral motor system.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
- Model description
- 3 week intervention with 15 sessions of add-on rTMS in 4 parallel arms, randomized, double-blind, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| Inhibitory repetitive transcranial magnetic stimulation (rTMS) | Experimental | Device: 1 Hz rTMS1 Hz stimulation of 17 mins over the supplementary motor area (SMA), 1000 pulses at 110% resting motor threshold intensity total of 15 sessions in 3 weeks |
| Facilitatory intermittent theta burst stimulation (iTBS) | Active comparator | Device: iTBSIntermittent theta burst stimulation of 50 Hz over the supplementary motor area (SMA) with 600 pulses in 2 sec trains every 10 seconds for 190 seconds total. Two iTBS stimulations will be administered with 15 mins pause in between. total of 15 sessions in 3 weeks |
| Placebo | Placebo comparator | Drug: Placebo1 Hz stimulation of 17 mins over the supplementary motor area (SMA) without any magnetic emission using a placebo-coil that looks identical and makes identical sounds as the real TMS coil total of 15 sessions in 3 weeks |
| Waiting group | No intervention | –This group will receive no intervention for 3 weeks. Afterwards they will receive the inhibitory rTMS protocol as in the first arm |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Right-handed subjects
- Ability and willingness to participate in the study
- Ability to provide written informed consent
- Informed Consent as documented by signature
- Schizophrenia spectrum disorder according to diagnostic and statistical manual version 5 (DSM-5) criteria with current psychomotor slowing according to the Salpetriere Retardation Rating Scale (SRRS), score >= 15
Key exclusion criteria (12 listed)
- Substance abuse or dependence other than nicotine
- Past or current medical or neurological condition associated with impaired or aberrant movement, such as brain tumors, stroke, M. Parkinson, M. Huntington, dystonia, or severe head trauma with subsequent loss of consciousness.
- Epilepsy or other convulsions
- History of any hearing problems or ringing in the ears
- Standard exclusion criteria for MRI scanning and TMS; e.g. metal implants, claustrophobia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1 Hz rTMS1 Hz stimulation at 110% of resting motor threshold over supplementary motor area | Device | Inhibitory repetitive transcranial magnetic stimulation (rTMS) |
| iTBS50 Hz theta burst stimulation at 80% of resting motor threshold over supplementary motor area | Device | Facilitatory intermittent theta burst stimulation (iTBS) |
| Placebo1 Hz stimulation with the placebo TMS coil without any magnetic emission | Drug | Placebo |
Primary outcome
Proportion of responders at week 3
Time frame: Week 3
Proportion of participants with >30% reduction from baseline in the Salpetriere Retardation Rating Scale (SRRS)
Change in Salpetriere Retardation Rating Scale (SSRS) from baseline
Time frame: Week 3, week 6, week 24
Change in the Salpetriere Retardation Rating Scale (SRRS) from baseline; the total score of 15 items is used, ranging 0-60 with higher scores indicating worse outcome
11 secondary outcomes
Change in catatonia severity from baseline to week 3
Time frame: Week 3, week 6, week 24
Change in negative symptoms from baseline
Time frame: Week 3, week 6, week 24
Change in psychosis severity from baseline
Time frame: Week 3, week 6, week 24
Change in physical activity self report from baseline
Time frame: Week 3, week 6, week 24
Change in objectively measured physical activity from baseline
Time frame: Week 3, week 6, week 24
Change in dexterity from baseline
Time frame: Week 3, week 6, week 24
Change in cortical excitability of the motor cortex from baseline
Time frame: Week 3, week 6, week 24
Change in social and community functioning
Time frame: Week 3, week 6, week 24
Change in functional capacity
Time frame: Week 3, week 6, week 24
Change in functional connectivity
Time frame: Week 3
Change in resting state cerebral perfusion
Time frame: Week 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2023.
- Derived from this study: PubMed 38416468Walther S, Alexaki D, Weiss F, Baumann-Gama D, Kyrou A, Nuoffer MG, Wuthrich F, Lefebvre S, Nadesalingam N. Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation: A Randomized Clinical Trial. JAMA Psychiatry. 2024 Jun 1;81(6):563-571. doi: 10.1001/jamapsychiatry.2024.0026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sebastian Walther, MD principal investigator
University of Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 1 Hz rTMS and iTBS in people with Schizophrenia and Related Disorders and Schizophrenia, run by University of Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of responders at week 3 (time frame: Week 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03921450, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2023.