Clinical trial NCT01392885: Brain Health and Exercise in Schizophrenia
Official title: Brain Health: Effects of Exercise on Hippocampal Volume and Memory Deficits in Persons With Schizophrenia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Schizophrenia
Schizoaffective Disorder
Poor Memory
Keywords: Schizophrenia
Schizoaffective Disorder
Brain Health
Exercise
Mental Health
Poor memory
Lead sponsor: BC Mental Health and Addictions Research Institute
Sponsor class: OTHER_GOV
Collaborators: name: University of British Columbia
name: Simon Fraser University
name: Canadian Institutes of Health Research (CIHR)
First posted: 2011-07-13
Enrollment: 60
Sex: ALL
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Sixty in-patients with chronic schizophrenia will be recruited at UBC Hospital and 60 age and gender-matched healthy (asymptomatic) community volunteers will be recruited through local community paper advertisements or posters at local community centres.

Brief summary: To determine the effects of aerobic exercise on hippocampal volumes and severity of psychotic symptoms in a population of psychosis patients compared to healthy age/gender matched volunteers. Psychosis patients often suffer from a number of cognitive difficulties, including poor memory function, poor problem-solving capacity and difficulties with attention and concentration. Poor fitness and associated neurovascular deficits may arise from various sources, including poor mental health, adverse side effects of antipsychotic medications and independent cardiovascular deficits that may be due to neurodevelopmental abnormalities in patients with schizophrenia. These factors are likely contributing to markedly increased stroke risk and early mortality. These problems are not well addressed by current clinical treatments, nor is neurovascular stroke risk readily or accurately detected in clinic.In contrast, evidence from aging research strongly suggests that increased cardiovascular fitness may provide numerous cognitive benefits by promoting brain growth, particularly in the frontal lobes and the hippocampi, while reducing the risk of stroke. The current study will measure the effects of aerobic exercise on brain volumes in a population of chronic psychosis patients to determine if 1) hippocampal volumes increase in response to exercise and 2) if parallel improvements in cognitive functioning occur. Additionally, baseline and follow-up stroke risk will be assessed using a novel non-invasive approach of retinal imaging to determine the presence of underlying neurovascular pathology.

Detailed description: This is a 12-week, randomized trial with two parallel groups. Throughout the trial, subjects will be treated on their prescribed dose of medication. Once informed consent is obtained, subjects and healthy volunteers will be randomly assigned to either an aerobic or a resistance exercise program (N = 30 per diagnostic group in each of two exercise conditions). Patients will continue to receive their antipsychotics and other prescribed medications. Healthy volunteer data will be used to establish normal exercise-induced neuroplasticity in a non-psychiatric, non-medicated population and to establish differences in retinal vessel integrity between patients and healthy volunteers. All training will be conducted at the UBC Hospital and at dedicated exercise training facilities at the University of British Columbia. All fitness assessments (based on the initial 6-minute walk test) and exercise sessions will be monitored by trained research assistants (RAs) under the guidance of the Canadian Society for Exercise Physiology-Certified Exercise Physiologists (CSEP-CEPs). The RAs will receive pre-study exercise training from the CSEP-CEPs. During the course of the study, the training intensity will be changed according to the individual participant's response and needs via the CSEP-CEPs and RAs.

Clinical data (current medications, current diagnoses, symptom profiles, resting heart rate, blood pressure, weight) will be collected on the hospital wards at baseline and follow-up. Neuroimaging and retinal imaging will be ascertained at the UBC MRI Research Centre at baseline and follow-up. Concurrent baseline assessments of executive functioning, memory capacity and crystallized IQ will be performed at baseline. Cognitive measures, excluding IQ, will be re-assessed at follow-up. Follow-up measures will only be collected in cases were patients are still available and willing to participate in study activities.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 45 years
* Able to provide written, informed consent in English
* Patients may be on prescribed medications
* DSM-IV diagnosis of schizophrenia or schizoaffective disorder
* Normal visual acuity (or normal visual acuity achievable with corrective lenses)
* Physical ability to be engaged in a regular exercise program

Exclusion Criteria:

* A history of organic disorders (dementia, severe head injury, or developmental disorders such as autism, mental retardation, Down's Syndrome)
* A current DSM-IV diagnosis of substance dependence (during prior 12 months, excluding tobacco)
* Any history of DSM-IV diagnoses (Axis I) for other psychiatric disorders
* History of angina, heart attack or transient ischemic attacks
* Non-independent mobility or limb prostheses
* A history of severe head injury leading to loss of consciousness for \> 5 minutes
* Contra-indications for neuroimaging (metal implants, non-removable orthodontic devices, severe claustrophobia, pregnancy, or surgeries within the previous 6 months)
* Currently already enrolled in a regular exercise program

Primary outcomes:
measure: Increase hippocampal volume with aerobic training in schizophrenic and healthy volunteers.
timeFrame: Base-line, 8 and 12 weeks
Secondary outcomes:
measure: Increases in hippocampal volumes will be positively associated with improvements in working memory performance in schizophrenia.
timeFrame: Baseline, Week 4, 8 and 12.
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: UBC Hospital
state: British Columbia
Study officials:
affiliation: University of British Columbia, Dept. of Radiology
name: Donna J Lang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia, Dept of Psychiatry
name: William G Honer, Professor
role: STUDY_CHAIR
affiliation: Simon Fraser University
name: Allen Thornton, Unspecified
role: STUDY_CHAIR
affiliation: University of British Columbia, Dept. of Human Kinetics
name: Darren Warburton, Ass. Prof
role: STUDY_CHAIR
affiliation: University of British Columbia, Dept. of Radiology
name: Alexandra T Vertinsky, Clin. Instr.
role: STUDY_CHAIR
affiliation: University of British Columbia, Dept. of Radiology
name: Alexander Rauscher, Ass. Prof.
role: STUDY_CHAIR
References:
citation: Woodward ML, Gicas KM, Warburton DE, White RF, Rauscher A, Leonova O, Su W, Smith GN, Thornton AE, Vertinsky AT, Phillips AA, Goghari VM, Honer WG, Lang DJ. Hippocampal volume and vasculature before and after exercise in treatment-resistant schizophrenia. Schizophr Res. 2018 Dec;202:158-165. doi: 10.1016/j.schres.2018.06.054. Epub 2018 Jun 29.
citation: Kim DD, Lang DJ, Warburton DER, Woodward ML, White RF, Barr AM, Honer WG, Procyshyn RM. Heart-rate response to alpha2-adrenergic receptor antagonism by antipsychotics. Clin Auton Res. 2017 Dec;27(6):407-410. doi: 10.1007/s10286-017-0444-4. Epub 2017 Jul 3.