Clinical trial NCT03921450: Overcoming Psychomotor Slowing in Psychosis (OCoPS-P)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia and Related Disorders
Schizophrenia
Schizoaffective Disorder
Brief Psychotic Disorder
Keywords: motor behavior
psychomotor slowing
psychosis
Lead sponsor: University of Bern
Sponsor class: OTHER
First posted: 2019-04-19
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3 week intervention with 15 sessions of add-on rTMS in 4 parallel arms, randomized, double-blind, placebo-controlled
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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.

Primary outcomes:
measure: Proportion of responders at week 3
timeFrame: Week 3
measure: Change in Salpetriere Retardation Rating Scale (SSRS) from baseline
timeFrame: Week 3, week 6, week 24
Secondary outcomes:
measure: Change in catatonia severity from baseline to week 3
timeFrame: Week 3, week 6, week 24
measure: Change in negative symptoms from baseline
timeFrame: Week 3, week 6, week 24
measure: Change in psychosis severity from baseline
timeFrame: Week 3, week 6, week 24
measure: Change in physical activity self report from baseline
timeFrame: Week 3, week 6, week 24
measure: Change in objectively measured physical activity from baseline
timeFrame: Week 3, week 6, week 24
measure: Change in dexterity from baseline
timeFrame: Week 3, week 6, week 24
measure: Change in cortical excitability of the motor cortex from baseline
timeFrame: Week 3, week 6, week 24
measure: Change in social and community functioning
timeFrame: Week 3, week 6, week 24
measure: Change in functional capacity
timeFrame: Week 3, week 6, week 24
measure: Change in functional connectivity
timeFrame: Week 3
measure: Change in resting state cerebral perfusion
timeFrame: Week 3
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Hospital of Psychiatry
Study officials:
affiliation: University of Bern
name: Sebastian Walther, MD
role: PRINCIPAL_INVESTIGATOR
References: