Clinical trial NCT03509597: Brain Image Markers Associated With Cognitive Training and Aerobic Exercise in Schizophrenia
Official title: A Randomized, Open-Label, Parallel-Group Study to Investigate The Effect of Cognitive Training and Aerobic Exercise on Brain, Functional Outcome and Cognition in Schizophrenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Schizophrenia
Keywords: Cognitive remediation
Aerobic exercise
Physical exercise
Negative symptoms
Functional outcome
Cognition
Lead sponsor: Red Salud Mental Araba
Sponsor class: OTHER_GOV
Collaborators: name: University of Deusto
name: University of the Basque Country (UPV/EHU)
First posted: 2018-04-26
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized parallel assignment: Cognitive Training, Aerobic Exercise \& Treatment as usual.
Primary purpose: TREATMENT

Brief summary: This study evaluates the brain correlates of Cognitive Training and Aerobic Exercise in schizophrenia. A third of participants will receive Cognitive Training plus Standard Care for schizophrenia. Another third of participants will receive Aerobic Exercise Training plus Standard Care for schizophrenia. A control group will of participants will receive Standard Care plus Occupational Activities for the same duration and frequency as the experimental groups.

Detailed description: This study, randomized, open, controlled with schizophrenia-standard-care, is aimed to determine structural and functional brain changes associated to cognitive remediation and physical exercise in schizophrenia.

The study participants will be enrolled in the catchment area of the Hospital Psiquiatrico de Alava, in the province of Alava, Basque Region, Northern Spain.147 patients diagnosed with schizophrenia will be randomly assigned to Cognitive Training Group or Aerobic Exercise Group or a Control Group for a five-month period.

Both Cognitive Training Group patients and Aerobic Exercise Group patients will participate in training sessions of 60 min/d, 3 d/wk. Patients assigned to Control Group will receive the standard care for schizophrenia in this area plus occupational activities for the same duration and frequency than the two experimental groups.

Cognitive Training will be implemented through REHACOP, a cognitive remediation program for Spanish speaking patients with schizophrenia whose efficacy on cognitive performance and negative symptoms has already been demonstrated in patients with schizophrenia. REHACOP is a "paper \& pencil" based cognitive remediation program that covers 8 cognitive domains including social cognition. It is based on the principles of Optimization, Restauration \& Compensation.

Aerobic Exercise Training will consist of an intensive physical exercise program supervised by certified graduates and doctorate students of Physical Activity and Sport Sciences. Sessions will include 10-minute warming-up and 10-minute back exercises and stretches. The main part of the session will consist of aerobic exercise (20-minute indoor bicycle) and muscle-resistance and strength exercises for 20 minutes. The intensity of the sessions will be determined on a case by case basis according to the HR necessary to achieve the intensity ranges (R2-moderate and R3-high). During the sessions, the bicycle's power and pace will be individually adjusted to achieve the selected HR.

The assessment batteries, neuroimaging and Serum BDNF levels will be administered and determined at baseline and immediately following the completion of the Cognitive Remediation or Aerobic Exercise interventions.

Primary outcomes: Structural and functional brain changes will be assessed by MRI neuroimaging. A Philips Achieva 3.0T MRI system equipped with a modular 32-channel architecture. 3 different types of images will be acquired: a) T1-weighted MRI imaging, b) Diffusion Tensor imaging, c) fMRI imaging at rest and using a cognitive paradigm.

Secondary outcomes will be changes in cognitive performance, clinical and functional changes and Serum BDNF changes.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Schizophrenia (DSM-5 F20.9)
* More than 2 years since the onset of the disease.
* Stable cognitive impairment.
* Moderate severity of cognitive impairment in MATRICS scores (T score \< 40 in, at least, 1 out of 7 cognitive domains).

Exclusion Criteria:

* Subjects clinically unstable (PANSS positive score \> 19).
* Cognitive impairment due to another medical condition (neurocognitive disorders, brain injury, intellectual disability, etc.)

Primary outcomes:
measure: Grey Matter Volume Change
timeFrame: 5 months
measure: Fractional Anisotropy Change
timeFrame: 5 months
measure: Functional Magnetic Resonance Imaging (fMRI) Change at Rest
timeFrame: 5 months
measure: Functional Magnetic Resonance Imaging (fMRI) Change during the performance of a cognitive paradigm.
timeFrame: 5 months
Secondary outcomes:
measure: Serum BDNF
timeFrame: 5 months.
measure: Clinical Symptoms of Schizophrenia measured by the Positive and Negative Symptoms Scale (PANSS).
timeFrame: 5 months.
measure: Negative Symptoms of Schizophrenia measured by the Brief Negative Symptoms Scale (BNSS).
timeFrame: 5 months
measure: Negative Symptoms of Schizophrenia measured by the Clinical Assessment Interview for Negative Symptoms Scale (CAINS)
timeFrame: 5 months
measure: Functional Outcome measured by the UCSD Performance Based Assessment of Functional Skills in Severe Mental Illness (UPSA).
timeFrame: 5 months
measure: Functional Outcome measured by the World Health Organization Disability Assessment Schedule (WHODAS 2.0).
timeFrame: 5 months
measure: Functional Outcome measured by the Short Form (36) Health Survey (SF-36).
timeFrame: 5 months
measure: Physical Condition measured by the Modified Shuttle Walking Test
timeFrame: 5 months
measure: Cardiorespiratory Fitness measured with the Peak Oxygen Uptake (VO2 max)
timeFrame: 5 months
measure: Weight.
timeFrame: 5 months
measure: Height
timeFrame: 5 months
measure: Body composition measured with Body Mass Index (BMI)
timeFrame: 5 months.
measure: Abdominal Perimeter
timeFrame: 5 months
measure: Body Composition measured with Total Body Water.
timeFrame: 5 months
measure: Body Composition measured with Body Fat.
timeFrame: 5 months
measure: Blood Pressure (systolic and diastolic)
timeFrame: 5 months
measure: Fasting Blood Glucose Levels
timeFrame: 5 months
measure: Fasting Cholesterol Levels
timeFrame: 5 months
measure: Daily Physical Activity and Sedentary Behavior measured by the International Physical Activity Questionnaire.
timeFrame: 5 months
measure: Level of Daytime Sleepiness measured by Epworth Sleepiness Scale (ESS)ESS-EPWORTH.
timeFrame: 5 months
measure: Intensity of Daily Physical Activity measured by the Accelerometer.
timeFrame: 5 months
measure: Cognition-Processing Speed
timeFrame: 5 months
measure: Cognition-Attention/Vigilance Stroop Test
timeFrame: 5 months
measure: Cognition-Working Memory Digit Span Backward
timeFrame: 5 months
measure: Cognition-Verbal Learning/Memory
timeFrame: 5 months
measure: Cognition-Reasoning/Problem Solving
timeFrame: 5 months
measure: Cognition-Cognitive Reserve
timeFrame: 5 months
measure: Cognition-Figural Creativity
timeFrame: 5 months
measure: Cognition-Verbal Creativity
timeFrame: 5 months
measure: Social Cognition-Social Attribution
timeFrame: 5 months
measure: Social Cognition-Emotion Recognition
timeFrame: 5 months
measure: Social Cognition-Theory of Mind
timeFrame: 5 months
measure: Social Functioning measured by the Social Functioning Scale Short-Form (SFS-15)
timeFrame: 5 months
measure: Self-Efficacy measured by the General Self-Efficacy Scale
timeFrame: 5 months
measure: Social Anhedonia measured with the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)
timeFrame: 5 months
measure: Handedness measured by the Edinburgh Handedness Inventory
timeFrame: 5 months
measure: Treatment satisfaction measured by the Spanish version of Consumer Reports Effectiveness Scale (CRES-4)
timeFrame: 5 months
Other outcomes:
Locations:
city: Vitoria
country: Spain
facility: Hospital Psiquiatrico de Alava. Red Salud Mental de Araba
state: Alava
Study officials:
affiliation: Hospital Psiquiatrico de Alava. Red de Salud Mental de Araba.
name: Pedro M Sanchez Gomez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanchez P, Pena J, Bengoetxea E, Ojeda N, Elizagarate E, Ezcurra J, Gutierrez M. Improvements in negative symptoms and functional outcome after a new generation cognitive remediation program: a randomized controlled trial. Schizophr Bull. 2014 May;40(3):707-15. doi: 10.1093/schbul/sbt057. Epub 2013 May 18.
citation: Ojeda N, Pena J, Bengoetxea E, Garcia A, Sanchez P, Elizagarate E, Segarra R, Ezcurra J, Gutierrez-Fraile M, Eguiluz JI. [REHACOP: a cognitive rehabilitation programme in psychosis]. Rev Neurol. 2012 Mar 16;54(6):337-42. Spanish.
citation: Pena J, Ibarretxe-Bilbao N, Sanchez P, Uriarte JJ, Elizagarate E, Gutierrez M, Ojeda N. Mechanisms of functional improvement through cognitive rehabilitation in schizophrenia. J Psychiatr Res. 2018 Jun;101:21-27. doi: 10.1016/j.jpsychires.2018.03.002. Epub 2018 Mar 6.
citation: Pena J, Ibarretxe-Bilbao N, Sanchez P, Iriarte MB, Elizagarate E, Garay MA, Gutierrez M, Iribarren A, Ojeda N. Combining social cognitive treatment, cognitive remediation, and functional skills training in schizophrenia: a randomized controlled trial. NPJ Schizophr. 2016 Nov 9;2:16037. doi: 10.1038/npjschz.2016.37. eCollection 2016.
citation: Ojeda N, Pena J, Bengoetxea E, Garcia A, Sanchez P, Elizagarate E, Segarra R, Ezcurra J, Gutierrez-Fraile M, Eguiluz JI. [Evidence of the effectiveness of cognitive rehabilitation in psychosis and schizophrenia with the REHACOP programme]. Rev Neurol. 2012 May 16;54(10):577-86. Spanish.
citation: Ojeda N, Pena J, Sanchez P, Bengoetxea E, Elizagarate E, Ezcurra J, Gutierrez Fraile M. Efficiency of cognitive rehabilitation with REHACOP in chronic treatment resistant Hispanic patients. NeuroRehabilitation. 2012;30(1):65-74. doi: 10.3233/NRE-2011-0728.
citation: Tous-Espelosin M, de Azua SR, Iriarte-Yoller N, MartinezAguirre-Betolaza A, Sanchez PM, Corres P, Arratibel-Imaz I, Sampedro A, Pena J, Maldonado-Martin S. Clinical, physical, physiological, and cardiovascular risk patterns of adults with schizophrenia: CORTEX-SP study: Characterization of adults with schizophrenia. Psychiatry Res. 2021 Jan;295:113580. doi: 10.1016/j.psychres.2020.113580. Epub 2020 Nov 18.